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Greetings from Maggie Bras Welcome to our 9th edition of the Helping Hand newsletter. During my husband Robert’s three and a half year battle with gallbladder and prostate cancer, it was brought to our attention the lack of new drugs available to treat cancer. With the helpful advice and partial funding from the Princess Margaret Cancer Foundation, we made an endowment to start up a new drug development program headed by Dr. Malcolm Moore. Its name would be The Robert & Maggie Bras and Family New Drug Development Program, recently shortened to the BRAS Drug Development Program. Robert did not live long enough to realize his and my dream and those of the Bras Drug Development Program, but our dream does live on in those who have fought bravely against their cancer and are winning or have won the battle! Today, I am pleased to bring to you the incredible progress made in the fight to conquer cancer. We are thrilled to announce that the Bras Drug Development Program has been successful in being awarded a large grant to support clinical and translational research in high grade serous ovarian cancer. This is one of the largest early phase trials set to profile women with ovarian cancer that incorporates robust clinical and biological endpoints. It is always delightful to meet our newest Fellows from around the globe who choose to study and work at the Bras Drug Development Program at the Princess Margaret Cancer Centre. We will catch up with two young women who were Fellows of the program and who are now employed as full time physicians and researchers at the BRAS DDP. We will meet Janet, a Phase l clinical trial patient, as she takes us through her cancer journey. We will take a moment to honour Lee Pettersen, who was an incredible advocate for Princess Margaret and The Bras DDP, and learn about the legacy she left behind. Dr. Amit Oza, who is one of the principle founders and now Director of the BRAS DDP, is a very busy man. Inside these pages you will find how Phase ll clinical trials examining DNA repair, can force cancer cell death, primarily in patients with mutations in BRCA1 or BRCA2 genes. We will be examining the role of Aspirin in women at a high risk of developing ovarian cancer; and a large phase ll study showing how cancer cells talk to one another. Once again we will meet up with Dr. Lillian Siu, one of the founders of the BRAS DDP and Co-Director of the BRAS DDP, who will speak about the Phase l program, which continues to advance new findings that help set the stage for future clinical trials of anticancer agents in development. And to congratulate Dr. Siu as the BMO Financial Group Chair in Precision Genomics in 2016 for a 10 year term. If that is not enough, we will learn about her Tumour Immunotherapy Program (TIP) at the Princess Margaret. Hopefully Lillian finds time to sleep! We will talk about Molecular Profiling in Advance Cancers Trial (IMPACT) and Community Molecular Profiling in Advanced Cancers Trial (COMPACT) which is being led by Dr. Phillippe Bedard along with Dr.Lillian Siu. I would like to take a moment to thank all our donors and supporters through the years who have contributed to the success of the Bras Drug Development Program. Because of your support, my family’s dream has become a reality. Thank you. Please take your time reading and learning about the progress made to date, and know that the BRAS Drug Development Program and Princess Margaret Cancer Centre are working extremely hard at slaying the beast we call cancer. Maggie Bras Website and to donate: www.BRASddp.com President, BRAS DDP Program Charitable Organization Number: 88900 75797 RR0001

Greetings From Hazel McCallion, Honorary Chair Of The Bras DDP As Honorary Chair of the BRAS Drug Development Program at the Princess Margaret Cancer Centre in Toronto, I value the work they are conducting, which is dedicated to the research and treatment of new drugs to treat cancer. Sadly, we all know someone who has been affected by cancer, and the BRAS Drug Development Program, under the directorship of Dr. Amit Oza, along with staff physicians, Drs. Lillian Siu, Philippe Bedard, Albiruni Razak, Eric Chen, Aaron Hansen, Anna Spreafico and Stephanie Lheureux has become a premier centre for early phase drug development and clinical trials. In addition, they are home to a world class Clinical Research Fellowship Program, headed by Dr. Philippe Bedard. The outstanding physicians and researchers who are working together to overcome this disease by designing the next-generation cutting-edge clinical trials, are helping us better understand how cancer begins, grows and ultimately, how it can be stopped! The community of dedicated and compassionate professionals behind this program, provides much needed hope to cancer patients, in order for them to live longer, healthier and more productive lives. Hazel McCallion

“We learn more by looking for the answer to a question and not finding it, than we do from learning the answer itself.” – Lloyd Alexander

Greetings from Dr. Peter Pisters, President and CEO of University Health Network Recognizing the Immeasurable Impact of the BRAS Drug Development Program on Patient Care. The BRAS Drug Development Program is one of the largest and most recognized drug development programs in Canada. Over the years, this remarkable program has witnessed substantial team growth and brought renewed hope to patients who have exhausted other treatment options. The lives of cancer patients have been improved, and even saved, thanks to you. Your dedication has helped The Princess Margaret Cancer Foundation achieve an historic milestone. This January, their fiveyear Billion Dollar Challenge was met – and surpassed – with $1.05 billion raised in support of personalized cancer medicine. Proactive, tailored therapies ensure that the right patient receives the right intervention at the most important time in their journey. As a result, Princess Margaret Cancer Centre has been able to expand its clinical research in key areas, including drug development, bringing a new drug to the market, and immunotherapy, which uses the body’s own immune system to fight cancer. The BRAS Drug Development Program, led by Co-Directors, Dr. Amit Oza and Dr. Lillian Siu, continues to attract internationally-recognized physicians and researchers. It is also a sought-after training centre for the brightest young medical minds from around the world who vie for Fellowships in the BRAS Program. When they return to their home countries, your support has a tremendous ripple effect, as they apply their new knowledge and skills to treat cancer patients around the globe. The team is transforming lives and communities through its Phase I and II Clinical Trials Programs, the largest in Canada and one of thirteen cancer centres outside of the United States which gets priority access to the most advanced experimental drugs by the U.S National Cancer Institute. The Princess Margaret Clinical Trials Consortium runs academic trials across Canada and internationally, and is a member of the Gynecologic Cancer Inter Group. Since 2011, the Consortium has made treatments available to over 1,600 cancer patients in more than 290 clinical trials. The results of these early phase clinical trials are published in national and internationally renowned journals, something that is critical to the success and transparency of cancer research. Thank you once again for sharing our vision to advance personalized cancer medicine. Your support for the dynamic work of the BRAS Drug Development Program is integral to The Princess Margaret’s ability to offer the best quality of life, care and treatment for every patient. Dr. Peter W. T. Pisters MD, MHCM, CPE, FACHE, FACS President and Chief Executive Officer, University Health Network

“Success is to be measured not so much by the position that one has reached in life, as by the obstacles which he has overcome while trying to succeed.” – Booker T. Washington, 1901

Greetings From Dr. Amit Oza Writing a letter of introduction for the 9th edition of Helping Hands always gives me pause to reflect on what the Bras Drug Development Program does, how far we have come, and where we are headed. Importantly, its also a ‘think and thank’ time - as none of this would be possible without the incredible support we receive - from our patients, staff, sponsors, Maggie and the Bras Family. More on this later. First what has the Bras Drug Development Program achieved over the past 16 years? (Yes, its 16 years!) The program which started with four doctors and a manager has grown into Canada’s largest and premier drug development program with 10 doctors and more than 80 staff including: nurses, coordinators, managers, fellows, and scientists. Importantly, the group has treated more than 5000 patients on over 200 clinical trials, developed and led by Bras DDP investigators from Princess Margaret and consortium sites throughout Canada. It has led the development of many new targeted anti-cancer drugs and immunotherapies, some of which have subsequently become established as major advances in treatment of several cancers. It has successfully trained new generations of cancer drug developers from Canada and internationally, who have taken the knowledge they gained in the Bras DDP with them to lead and work with trials programs in Australia, Europe, New Zealand, South America and the United States to name a few. Bras DDP has also spawned a new generation of personalized/precision therapies through major programs in Genomics, Immunotherapy, Translational Research and Ovarian Cancer. Over the past year, we have recruited some excellent new faculty members to the program—Dr. Anna Spreafico to Phase I, Head and Neck cancers and Melanoma, and Dr. Stephanie Lheureux to Phase II Drug Development and Gynecology, and they are both already leading cutting edge research in these areas. Bras DDP investigators continue to push the boundaries of our understanding of cancer and how we can advance the next generation of precision anti-cancer agents. Whether this means honing in on particular changes in the DNA of cancer, like targeting its Achilles’ heel, or harnessing the power of the immune system, the Bras Drug Development Program has contributed important new information over the last year to help conquer cancer. Drs. Lillian Siu and Phil Bedard have led the field looking at how to incorporate genomic testing to improve precision of cancer treatment. The team published its key findings from the first Canadian genomic profiling clinical trial, illustrating the ability to test tumours to assess if genomic mutations, which drive some cancers, can be targeted. Along with his colleagues, Dr. Bedard has built upon this success and launched the “Ontario-wide Cancer TArgeted Nucleic Acid Evaluation” (OCTANE) trial with four cancer centres across Ontario, to expand access to genomic testing and next generation sequencing capabilities in Ontario clinical genetic testing labs. There have also been major new programs initiated in women’s cancers, with significant new funding from major philanthropic donors, pharmaceutical companies and granting agencies. These new initiatives will allow us to learn from every patient – to understand why treatments work or fail, to understand the biology and importantly, to try and improve effectiveness of treatment using this information. These new programs are a testament to the courage of several of our patients, whose tireless resolve and strength were the driving motivation for the creation of two major efforts to advance research and development in gynecologic cancers (patients not named) – eVOLVE and BioDIVA. These programs will be a living legacy, which will help many more women in the future.

“We may encounter many defeats but we must not be defeated.” – Maya Angelou

Within the Phase II setting, our staff have been closely involved with participating in key trials examining the effect of PARP inhibitors (DNA-repair enzyme), exploiting key vulnerabilities in cancers such as ovarian, targeting this Achilles heel with well tolerated oral agents, which have now been approved for clinical use across the world. This year, our group was part of the international team that published findings from a large phase III trial of Niraparib, a PARP inhibitor, which showed efficacy in women with high grade serious ovarian cancer, whether they had BRCA1 or BRCA2 mutation. Findings from the study were published in the prestigious New England Journal of Medicine, and Niraparib has now received approval by regulatory authorities in the United States for the treatment of ovarian cancer as maintenance therapy after response to platinum based chemotherapy. In addition to breakthrough research discoveries, the pages of this year’s Helping Hands newsletter will highlight milestone programmatic activities, such as welcoming of several new faculty members who bring expertise in gynecologic, genitourinary and pancreatic cancers, cancers of the head and neck, as well as melanoma and immune therapy. Our new faculty significantly expands the expertise in drug development and has been actively developing and participating in high priority clinical research. You will also learn about several of our Clinical Research Fellows who have travelled from the farthest reaches of the globe to train from our internationally renowned faculty. Lastly, you will also discover that the Bras Drug Development Program has a new home immediately next door to Princess Margaret on the 7th Floor of 700 University Avenue. It’s nestled between Queen’s Park, the MaRS Discovery District and the University of Toronto. The new location ensures that our teams have direct access to state-of-the-art resources within an environment that fuels innovation. I invite you to read through the 2017 edition of Helping Hands and learn first-hand how each day the Bras Drug Development Program makes extraordinary contributions to cancer research and to the bright horizon ahead. Dr. Amit M. Oza Professor of Medicine, University of Toronto Head, Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network & Sinai Health System Director, Cancer Clinical Research Unit, Director, Bras Drug Development Program

“It’s amazing what you can accomplish if you do not care who gets the credit.” – Harry Truman

The Holy Walkamolies - The BRAS DDP Phase l Team “The Rexall OneWalk to Conquer Cancer is a life changing experience. It’s an experience that every year brings together thousands of walkers who take to the streets of Toronto to raise vital funds for cancer research and care at the Princess Margaret Cancer Centre, one of the top five cancer research centres in the world.” “The BRAS Drug Development Phase l group have put together a walking team of oncologists, researchers, co-ordinators, nurses and fellows. The money they raise will go directly to the BRAS Drug Development Program at The Princess Margaret Cancer Centre. www.brasddp.com” We are asking you to support our Phase l team – the HOLY WALKAMOLIES, as they embark on a 15, 25 or 40 kilometer walk, by donating to: www.onewalk.ca and search ‘Holy Walkamolies’ One Powerful Community. One Powerful Challenge. Dr. Philippe Bedard – Team Captain

The Bras DDP Landmark Grant Funding Announcement

Phase Il Team

Ontario Institute for Cancer Research and Ministry of Research, Innovation & Science We are thrilled to announce that the Bras Drug Development Program has been awarded a large grant to support clinical and translational research in high grade serous ovarian cancer. BRAS DDP’s Dr. Amit Oza and his Co-Principal Investigator Scientist, Dr. Robert Rottapel, will receive $9.9m in new funding from the Ontario Institute for Cancer Research (OICR) to support next-generation laboratory research and several early phase clinical trials through the Bras Drug Development Program. This investment will support an Ontario-wide program that will profile just over 250 women who have been diagnosed with high grade serous ovarian cancer. Over the next four years, the program will help identify the biology that drives this disease and how it can be overcome. This is one of the largest early phase trials set to profile women with ovarian cancer that incorporates robust clinical and biological endpoints. This investment will go towards leading discovery work to uncover how ovarian cancer develops, becomes resistant to treatment, and most importantly, how to overcome this clinically. The Ovarian Translational Research Initiative (TRI) leverages our Ontario-wide Princess Margaret Phase ll Consortium that allows findings from the lab to be directly tested in the clinical setting. With a total of nine clinical trials receiving support, Dr. Oza and the BRAS DDP are providing the clinical leadership alongside Drs. Stephanie Lheureux, Marcus Bernardini, Blaise Clarke, Sarah Ferguson, Anthony Joshua, Patricia Shaw, Lillian Siu and Anna Spreafico – Princess Margaret Cancer Centre - Toronto; Jacob McGee and Steven Welch - London Regional Cancer Program; Laurie Elit and Hal Hirte – Juravinski Cancer Centre – Hamilton; Al Covens and Helen Mackay – Sunnybrook Odette Cancer Centre – Toronto; Julie Francis and Jim Biagi – Cancer Centre of Southeastern Ontario – Kingston; and Joanne Weberpals and Michael Fung Kee Fung – Ottawa Regional Cancer Centre. The research grant also provides significant support to laboratory research activities, which are being led by Dr. Robert Rottapel and include internationally respected scientists; Drs. Ken Adalpe, Laurie Ailles, Daniel DeCarvalho, Benjamin Haibe-Kains, Pamela Ohashi and Trevor Pugh – Princess Margaret Cancer Centre; Daniel Durocher – Lunenfeld-Tanenbaum Research Institute; Trevor Shepherd – London Health Research Institute and Madhuri Kot – Queen’s University. Congratulations to Dr. Amit Oza of the BRAS DDP and his Co-Principal Investigator Scientist, Dr. Robert Rottapel, together with Ontario’s brightest scientists and clinicians who are undertaking this important task. We wish them all the best. “Strength does not come from physical capacity. It comes from indomitable will.” - Gandhi

Believe in Fashion was a dream, which became a reality in 2012. Our vision was to take our love for fashion and use this as a vehicle to raise funds for the BRAS Drug Development Program at Princess Margaret Cancer Centre. And we did just that! In 2012, The Room at Hudson’s Bay became our presenting sponsor with the incredible support of President and Buying Director, Nicholas Mellamphy. Nicholas was able to secure New York designer – Narciso Rodriguez, who showcased his collection in Canada for the very first time! Our show was a delightful success, raising $135,439!* In 2014 The Room at Hudson’s Bay once again partnered with Believe in Fashion, and Nicholas Mellamphy secured world renowned, London based fashion designer, Erdem Moralioglu. Born in Canada, Erdem became a huge international success in the UK. We were honoured to be the recipient of Erdem, showcasing his collection for the very first time on Canadian soil. Our show was another success raising $167,498* for the BRAS Drug Development Program.

Our success could not be possible without the help of many dedicated individuals. A tremendous “thank you” to Jeanne Beker, Nicholas Mellamphy, Kathy Hilton, Suzanne Rogers, Sylvia Mantella, Korby Banner, Kara Alloway, Raymond Elias, Beverley Mahood, Kenny Munshaw, Lee Pettersen, Princess Margaret Cancer Foundation and all of our sponsors and patrons who supported and attended Believe in Fashion. We will continue our dream of combining our love for fashion to raise funds for the BRAS Drug Development Program! Please stay tuned. With our gratitude, Maggie Bras, Holly Miklas, Tracey Neziol, Co-Chairs Kathy Hilton, Honorary Chair For full image gallery, please visit www.BRASddp.com *All proceeds from Believe in Fashion go to support the BRAS DDP at The Princess Margaret Cancer Centre.

Understanding Clinical Trials – What is a Phase l Trial? Phase l clinical trials are the bridge between the laboratory and the clinic. They represent the first time a promising new agent, which has been tested extensively in the lab, is given to humans. The purpose is to understand what the drug does to the body and what the body does to the drug. The goal is to determine whether it’s safe and whether there is any hint of activity to warrant further development. Each time a first-in-human (Phase l), or first-in-class study begins, it’s a unique exploration. There are no roadmaps. There are hypotheses and expectations, but certainly no guarantees. Investigators must observe and attend to every detail, translate their patients’ experiences and transmit them from the front line for the benefit of the entire field. Decisions to abandon or pursue tomorrow’s treatments start here and they’re based on stories from this vanguard. Phase l really is cancer medicine’s first frontier.

Phase I Program: The Phase I Program at Princess Margaret Cancer Centre is the largest in Canada and is recognized internationally as a leader in first-in-human clinical trials. It’s one of thirteen cancer centres (the only non-pediatric centre outside of America) selected by the U.S. National Cancer Institute to receive a Phase I UM1 grant, which gives it priority access to the most advanced experimental cancer drugs in the field. This means patients at the Princess Margaret participate in some of the most important investigations in the world! The program is comprised of five Principal Investigators, several clinical research fellows-all fully qualified and certified Medical Oncologists – one program manager, two assistant program managers, one financial manager, eight clinical trial nurses (including two nurses who handle drug administration and pharmacokinetic blood sampling), one pharmacist, one tissue coordinator for molecular pre-screening, sixteen data coordinators, one grants and contracts specialist, and one biostatistician. Eight to ten new patients are seen each week in the Phase I clinic, referred by staff within the Cancer Centre and by community oncologists across the country. This amounts to 400-500 new patients each year, which means that there are consistently more patients than trial slots available. It also means that the Program’s referral base is large enough to support the opening of many more studies. The Program has been designed for both collaboration and expansion. It is closely linked to the Cancer Genomics Program at Princess Margaret, which helps identify molecular variants for investigational drug trials by sequencing tumour DNA, as well as to the Tumour Immunotherapy Program, which develops immune oncology trials that are initiated by an investigator, and sponsored by a pharmaceutical company to further strengthen cross-disciplinary ties. Program teams regularly partner with other research groups, including radiation oncology, surgical oncology and pathology. These synergies have helped the Phase I Program evolve rapidly. From 2014-2016, more than 1300 patients were treated in clinical trials at the Princess Margaret; among them, over 220 were treated in Phase I first-in-human trials. Editor’s note: For a more in-depth look at Phase l studies with new immune-oncology targets and examples, please go to: www.brasddp.com

Janet’s Journey: Phase l Clinical Trial Patient

YOU HAD PAIN FOR A LONG TIME BEFORE YOU WERE DIAGNOSED? “I did. I’d had ultrasounds and colonoscopies and blood tests. Nothing. Finally, the pain got so bad that I went to Emergency. It was February 14th, Valentine’s Day. By midnight, they’d given me a CT scan and told me they were going to admit me. They knew what was wrong, but they weren’t telling us. The next morning, the surgeon came in – at six in the morning, because that’s when they’re free- and he woke me up. I had to ask. He looked down at me and said, “I’m almost certain you have colon cancer.” Three weeks later I had my surgery. For the next year I did chemo. I’d do chemo on a Wednesday or Thursday, every two weeks. Then I’d go home with what I call the “baby bottle” – I’d be connected for two days. Three days later, I’d be out for the count for a couple of days, just so fatigued. So then you’re into the next week. You just start to feel better, and then you start it all over again. It just ravages your body. Fourteen months into my chemo I got very sick. I was in the hospital for 17 of the 30 days in June. Lying in my hospital bed, I thought that’s it, the chemo’s stopped working and I’m dying. Your whole family, everybody who loves you, is watching this happen and everybody’s trying to keep a stiff upper lip. My husband was ready to sell everything we had and take me to the Mayo Clinic. But my darling surgeon, he saved my life. He debated for two full days about doing a second surgery and decided not to. And eventually I got better.”

HOW DID YOU MAKE THE DECISION TO JOIN THE PHASE l TRIAL? “When I came out of the hospital, I said to my doctor: “What about that trial my husband found last year”? The chemo I was on was palliative anyway. It wasn’t going to work and we knew that from the beginning. When I first went on long-term disability from work, my sister came with me to the

hospital to pick up the insurance paperwork. We got as far as the parking lot before we opened it. Make her “feel comfortable” were the words the oncologist had written, I think. We both burst into tears. I said: This is not going to be me! When I went down to Princess Margaret and went through all the tests, they told me I was a match – which is to say, I had a cell mutation that was genetic. Only ten percent of the world has it, and it makes your body turn on itself. Lucky me, right? They give you this document about the trial and the drug, probably 20 pages that you’ve got to read before anything else can happen. And I mean, it scares the bejesus out of you. Because you read that two people had died! My husband is a lawyer, just retired. He read it and I read it and we re-read it. He said: “You know, yes, two people died. But look at all the rest who are still here.”

WHAT EXPECTATIONS DID YOU HAVE, IF ANY? “I’ve got a friend whose mother just passed away at 92. Thirty years ago she was diagnosed with breast cancer and they told her to go home and put her affairs in order. But then they said we’ve got this drug called Tamoxifen, and would she be willing to go on a drug trial? She just passed away. At 92! Tamoxifen was the equivalent in her time – it was the last resort. It may not have worked for every woman, but it gave hope and treatment to a whole generation. My own options were not great. So, I thought, what do I have to lose? When I met Lee-Anne, my clinical trials nurse, and Dr. Lillian Siu and Dr. Anna Spreafico, they were all very upfront. How can I say it? The people I met are the people they are. On the drug trial, they never promised me a rose garden. They never promised me anything other than, “You’re a good match, and let’s try.” They’ve been completely professional yet very empathetic at the same time. I said to my sister, “I’m going to take this drug and see, and if I don’t come out of it, promise that you’re going to look after my kids.”

“The butterfly counts not months but moments, and has enough time.” – Rabindranath Tagore

WHAT HAPPENED AFTER YOU SIGNED THE FORM? “I started on the treatment. For the first week, you’re seeing doctors every single day. Every day! By Friday, I had a rash on my leg. I didn’t understand that the rash was a reaction to the drugs. They gave me cream and they changed the medication dose immediately. Dr. Albiruni Razak, who is the research doctor, called me first thing Saturday to follow up. The rash was gone. I felt better. Still, he wanted to examine me in person to make sure. He ended up working around my schedule and seeing me at 9:00 AM on Labour Day, Sunday. That’s the kind of access you have to your doctors when you’re in a drug trial. I’ve never had this kind of access to doctors.”

WHAT’S YOUR EXPERIENCE BEEN LIKE SINCE THEN? “Every Tuesday I’m up and out the door by 5:30. We drive down to Princess Margaret and I have blood work done, and then I see the research doctor or Dr. Siu. Once my blood work is okay, I have an infusion, which is only an hour. Every second week, I have a two-hour infusion of magnesium, so it’s a longer day for me. Every sixth week I have a CT scan so they know where this illness of mine is. I see an ophthalmologist every two or three months. I see a dermatologist every two or three months, because this drug can cause melanoma. They’ve taken off about six moles, of which one has had cancer. But they caught it!”

way with most patients. Once you get into this kind of system, they check your expectations. Dr. Siu has told me many times: “These drugs will eventually stop working. They always do.” If and when they do, I’ll do something else. I would try another drug trial. If chemo was my only option, I would try chemo again. And if there was nothing else, and I was in a lot of pain, I’d say it’s time for me to go. I’m very pragmatic. If you tell me how it is, I will deal with it. I don’t know why God dumped me on this journey, but he has. Sometimes I think it’s just to make somebody else feel good for five minutes when we are in that hospital together.”

WHERE DO YOU GO FROM HERE? “Since I started this trial, I’ve gotten two years that I shouldn’t have. That’s given me more time with my family. I’ve welcomed two beautiful grandchildren into this world and now we’ve got another one on the way. My husband, Aleks, my rock, my constant source of strength – he and I know what this time means. We see our kids as much as we can. We’ve managed to have two trips to Europe and to go south a couple of times. We make new memories every day. I’ve been lucky that the drug company will maneuver around my schedule where they can. I’ve managed to do it with the help of Dr. Siu and her team. She’s got a phenomenal team. And we’ve been lucky. I don’t know why it worked for me. I don’t know, but it’s working. Maybe tomorrow it won’t, but right now it’s doing everything we need it to do, and I’ve got my quality of life back.”

Dr. Siu is my doctor, but I also see her fellows, or if I have my CT scan results, then it might be Dr. Razak or Dr. Spreafico who I see. I do tend to see Dr. Siu more than most, but it could be any one of them depending on the week. No matter who it is, the attention and the understanding are there. They all know me and my trial and my health. Nothing is missed. They are a phenomenal group of people and we’re very lucky to have them. I don’t think we fully appreciate the hospital we’ve got here, right in Ontario! So Tuesdays, Princess Margaret owns me, and other than that, nothing. I take two pills each day for the study. It’s a normal existence, really.”

HAVE YOU HAD ANY OTHER COMPLICATIONS? “I’ve been lucky. I have not had any major side-effects. And it’s been TWO YEARS that it’s worked for me. I would say to anyone: If the chemo is not working, or whatever they are giving to you is not working, what have you got to lose? Maybe you’re going to help yourself. Maybe you’ll help somebody else, some mom or dad with small children. You don’t know. But someone has got to try. A month ago, I got my CT scan results. They said: “Janet, honestly we don’t know any more if you’ve got an active disease or not. The problem is, if we stop, we don’t know what will happen.” They are very, very straight up. I think they are that

Janet and Aleks make time for lunch at Momofuko, Toronto.

Editor’s note: Due to size, this article has been edited. To view complete article, please visit: www.brasddp.com Phase l BRASDDP Program booklet.

“To the world you may be one person; but to one person, you may be the world!” – Dr. Seuss

A NURSE’S STORY: Lee-Anne Stayner, Phase l Clinical Trials Nurse

Setting realistic expectations is a big part of Lee-Anne Stayner’s job: She’s a clinical trials nurse in the Phase l Program. Of course, she’s responsible for much more than that; patient care, leadership and administration. Lee-Anne is also responsible for obtaining and documenting informed consent from subjects. And for consent to be truly informed, the expectations must be very clear. “The doctor talks to them about the study, but doesn’t actually get their consent to participate, that’s me,” she explains. “I just try to be frank with people. I let them know it’s investigational, there’s no guarantee and it’s unlikely that there will be any benefit from the treatment, which is hard,” she explains. “You see patients almost wince when you make that statement. But you don’t want people going in with unrealistic expectations and then being unprepared for the possibility that their tumours aren’t going to shrink and their symptoms aren’t going to get better.” It’s a message every member of the Phase l team understands and delivers carefully: Phase l trials are not designed to benefit the subjects who participate in them. They are the first step in a long journey towards changing cancer care for the better – for the future. Do these clinicians aim to stretch out their subjects’ disease control as long as possible? Of course they do. Lee-Anne recounts the story of an elderly patient who asked her the odds of attending his granddaughter’s graduation a few months after starting his trial. Though no one in the team could (or would) promise it, they were all desperate to see it happen. That’s what’s so unique about this group of clinicians: Every day, they have to draw a clear line between hope and probability, between head and heart. They have to be faithful to their protocols and to their patients. And every day, they walk that line gracefully.”

As Lee-Anne points out, the dynamics in Phase l are very different to those of curative therapy. “Most of the patients that we see have been in the system for a while,” she explains. “They’ve had a lot of treatment and are familiar with what being part of anti-cancer treatment is all about. That’s changing a little bit now with these immunotherapy drugs – some people are trying these out first before anything else. But, by and large, our study patients have exhausted standard options. That’s how Janet came to us; her husband had found this trial and I think they saw it as a last chance.” The two first met when Janet came in to sign her consent form. Not long into the appointment, Janet broke down and started crying. “She was obviously very nervous about enrolling in the study,” Lee-Anne explains. “She’d had chemotherapy already and I think she was very concerned about running into the same side effects she’d experienced before, because they’d been really difficult for her. But, like a lot of patients, she didn’t want to have no treatment.” They talked for a long time. Lee-Anne learned that Janet had experienced an intestinal obstruction during chemotherapy and had ended up in hospital, believing she would never leave. Lee-Anne drew a red circle around that in her notes, reminding herself to watch for any side effects that could lead in that direction. She didn’t want Janet to feel the same anxiety she had during chemotherapy and she was in a position to do something about it. As a trials nurse, Lee-Anne sees the same patients, Janet included, week in and week out. She’s their primary contact, which makes her the gatekeeper when it comes to monitoring adverse events, escalating issues, and coordinating the wider team for consultation. She and her colleagues set patients up on their protocols and administer their treatments. They work to manage any side effects and investigate

“You may not control all of the events that happen to you, but you can decide not to be reduced by them.” – Maya Angelou

any problems. If a patient needs an ultrasound, hydration, a blood transfusion, a nurse will schedule and oversee those interventions. “There’s a lot of independence and there’s a lot of decision-making and critical thinking,” she reflects. “And, of course, much deeper relationships.” And that matters. “I worked in the Emergency Department before this,” LeeAnne says. “It was fast-paced and interesting, but I didn’t find that it was very rewarding in terms of the relationships you built with patients, because you didn’t really build them. You saw patients for one shift and you never saw them again. There was no continuity of care, you never knew what the outcome was.” In contrast, all of the patients in a Phase l trial have advanced cancer. “There’s an enormous effort made to get them screened and treated as soon as possible. If we don’t get them treatments quickly, they may progress. We have administrative staff who do a lot of our bookings, but sometimes a department is a bit behind – it happens – and you have to step in. You just have to get things done in this program, there is no time to wait.” This bias toward action is built into the Phase l Program itself. And it’s ingrained into every professional who joins the team. When Lee-Anne first started, there were just three nurses. She processed her blood samples in the centrifuge and shipped them herself with FedEx. Today, the Princess Margaret Correlative Studies Group looks after those logistics so that Lee-Anne and her colleagues can spend more time with patients. “There are nine of us nurses now,” she says. “Each is responsible for somewhere in the neighbourhood of 15-20 patients at a time. Our program has grown significantly over the time that I’ve been here, and it’s only getting better as it does.”

Lee-Anne Stayner Phase l Clinical Trials Nurse Bras Drug Development Program

Editor’s note: Due to size, this article has been edited. To view complete article, please visit: www.brasddp.com Phase l BRASDDP Program booklet.

“The best gift you can give is a hug: one size fits all and no one ever minds if you return it.” - Unknown

Dr. Lillian Siu – Director Phase l Program Identifying a target that isn’t ‘druggable’ is like glimpsing Achilles’ heel and realizing you have no poison arrows – another reason Janet’s story is so remarkable. Huge leaps in genetic technology have made it easier and more cost effective to profile tumour DNA, but the stockpile of agents ready to exploit this new knowledge is still being built up. That mismatch keeps the fire burning within early phase investigators, like Dr. Lillian Siu. Lillian leads the Phase l Solid Tumours Program as well as the Cancer Genomics Program at the Princess Margaret Cancer Centre. She also co-leads the Tumour Immunotherapy Program. The Centre holds all of these functions under one umbrella to stimulate cross-talk and collaboration during the very early stages of development, when the future of a drug is unwritten and all doors to discovery are best left open. “People say Phase lll trials are very important because they change standard, and I don’t want to argue with that,” Lillian says. “But I’d argue that to bring a drug from the baby stage to the childhood stage is equally important. It’s a critical period during which you can make or break a drug.” The Principal Investigators (PIs) who run Princess Margaret’s Phase l clinical trials, are all medical oncologists with highly specialized research training. They know well the risks to the patients on their studies: possible side effects, adverse events. But they also know the risks to future patients of green-lighting the wrong drug or stopping short the development of the right one. In this team, no decision is taken lightly. When the road gets bumpy, as it invariably does, the Pls are careful to examine whether something in the protocol should be flagged for discussion with sponsors and partners, or whether any important signs may have been missed, before drawing final conclusions. They are in constant contact with patients, assessing the tolerability of a given treatment. “It is a huge responsibility,” Lillian explains. “The data are critical, but data tell us more about what is happening than why it’s happening. You have to be able to recognize patterns. You need a deep working knowledge of drugs and interactions so you can develop hypotheses about what your patients are experiencing. Ultimately, the patients are giving you the answers. You have to listen to them, and watch them, and monitor them, because you can’t read about the toxicity of these drugs in a book. There is no book.” That’s what drew Lillian to this work in the first place. “I saw an ad in a cancer journal. It was describing this early drug development program in San Antonio which was, at that time in 1994, an area that was not pursued by many trainees. I was here at Princess Margaret, trying to decide on my subspecialty. I actually read the ad, which I never do, and that’s where it started. It felt like serendipity. In hindsight, I really think it was.” Lillian worked in Texas for a year. She absorbed everything she could from incredible mentors and returned to Toronto with a clear vision of what she wanted to build at Princess Margaret: a program that would consistently push the boundaries in drug development – a beacon for cancer centres in Canada and around the world. When the Phase l Program opened in 1998, they had three trials. Today, they have more than 40. “I could never have envisioned building a program quite like this,” Lillian admits. “Everybody feels such purpose. They know what they’re doing is important and they don’t want to fail anyone: patients, colleagues, or the program. They don’t want it to lose its cohesiveness, its quality. It’s definitely considered one of the top programs, not just in terms of science and research, but in terms of operational efficiency, quality and high standards. And yes, I’m saying this because it’s ours, but I think if you asked our peers, they would say the same.”

“Live simply, so other people can simply live.” - Unknown

Fellows from all over the world travel to Princess Margaret to learn the business of drug development – especially Phase l development, so that they can go home and build their own teams. “Phil – Dr. Bedard, who runs our fellowships, has a huge job because this is such an important aspect of what we do,” Dr. Siu explains. “We’re actually training the scientists who will go on to become our partners all over the world. It’s like they’re seeds that grow into trees that are growing seeds again.” Just like the ‘triad’ organization of Drug Development, Cancer Genomics, and Tumour Immunotherapy at Princess Margaret, the emphasis on Fellowship in Phase l is no accident. It’s a calculated move to harness growing momentum in cancer drug development and increase the overall pace of discovery. “The Program’s overall mission is to lead biomarker-driven early phase clinical trials of new cytotoxic, molecularly targeted and immune-oncology agents. This is how we advance the development of cancer therapeutics in Canada. In addition to this, through our fellowships, we’re actually growing the global capacity for first-in-human trials,” Lillian explains. “Very few programs in Phase l do this.” Dr. Bedard and the Principal Investigators hold weekly meetings with their Fellows to go through performance feedback. Fellows, after all, are on the front line: they get exposed to every trial and they see one another’s patients. “This is the very best way to learn how to be observant, how to recognize patterns, how to put it all together and tell a story,” Lillian says. “We absolutely stand alongside them. But we let them tell us their story and we provide feedback.” There is also a meeting every week for the entire Phase l team. “We talk about challenges and toxicities we’re seeing, anything we’re worried about,” says Lillian. “And it’s not just the doctors and the nurses talking. The coordinators are inputting as well. The fact that they are part of the decision-making body is very important. This is not a top-down, ‘a few people call the shots’ kind of program. Everyone here has a voice and a piece of the work.” But as much as this team values discourse, they also value speed. To compress time to study start-up and time to completion, all contracts are handled by a dedicated person who works specifically on Phase l trials and the Bras Drug Development Program. Lillian believes they get the opportunities they do, like first-patient-first-visit, because of the very structure of the team and how proficient each member is at his or her job. “We have an amazing system that we’ve created that means everybody knows everybody’s patients fairly well,” she explains. “You can have somebody absent for a meeting, going away, and somebody else can take over their care. So you don’t feel like, “my doctor is out of town”. It’s a team. It’s not one person.” If you look at the Program’s organizational chart, you’ll see very well-defined roles but also a great deal of cross-responsibility. Again, this is no accident. The team has built-in redundancies, allowing doctors and nurses to lead their own activities but also cover one another’s responsibilities as needed. Data coordinators have their own projects but have the flexibility to consult on all projects. Fast and frequent communication makes it rare for even small details to fall through the cracks. On top of that, this team is operating within one of the top five cancer centres in the world. “We have an excellent referral base because we have a big catchment area at Princess Margaret. We have the right science, we have the experts, and we have the support of the Institution who consider this an important program. All this together, plus the spirit of the Phase l Program, I think has taken it very far.” Editor’s note: Due to size, this article has been edited. To view the complete article, please visit: www.brasddp.com - Phase l BRASDDP Program booklet. Lillian Siu, MD, FRCPC BMO Chair in Precision Genomics Professor, University of Toronto Director Phase l Program Co-Director BRAS Drug Development Program Princess Margaret Cancer Centre, Toronto, Canada

“A mind without instruction can no more bear fruit than can a field, however fertile, without cultivation.” – Cicero

L-R: Dr. Aaron Hansen, Dr. Anna Spreafico, Dr. Lillian Siu, Dr. Albiruni Razak, Dr. Philippe Bedard

The Phase I Principal Investigators Dr. Lillian Siu Dr. Siu is a Senior Medical Oncologist at Princess Margaret Cancer Centre and Professor of Medicine at the University of Toronto. She is the Director of the Phase I Program, Co-Director of the Bras Drug Development Program, and BMO Financial Group Chair in Precision Genomics at Princess Margaret. She has served on the Board of Directors for the American Society of Clinical Oncology (ASCO) and as a member of the Nomination Committee for the American Association of Cancer Research (AACR). Lillian’s major research focus is new anti-cancer drug development, particularly with respect to Phase I trials and head and neck malignancies. She is the Principal Investigator of a Phase I cooperative agreement UM1 award (2014-2019) sponsored by the United States National Cancer Institute. In addition to her active research in early phase clinical trials, she leads genomics initiatives and immune-oncology trials at the Princess Margaret Cancer Centre. Internationally, Lillian was the recipient of the U.S. National Cancer Institute (NCI) Michaele C. Christian Award in Oncology Drug Development in 2010. She was the American Society of Clinical Oncology (ASCO) Conquer Cancer Foundation Grants Selection Committee Chair in 2009-10, Chairperson of the American Association for Cancer Research (AACR) Education Committee, and Co-Chairperson of the Scientific Committee for the 2012 Annual Meeting. Lillian is currently a scientific editor for Cancer Discovery. She also sits on the editorial board for the Journal of Clinical Oncology and JAMA Oncology.

Dr. Philippe Bedard Dr. Bedard is an Associate Professor of Medicine at the University of Toronto. He is Staff Medical Oncologist in the Division of Medical Oncology and the Fellowship Director for the Bras Drug Development Program at the Princess Margaret Cancer Centre. He received his medical degree from the University of Toronto where he was awarded the Cody Academic Silver Medal. He completed his Internal Medicine and Medical Oncology specialty training at the University of Toronto. He received additional fellowship training in Clinical and translational breast cancer research at the Breast International Group (BIG). The Conquer Cancer Foundation of the American Society of Clinical Oncology (ASCO) recognized Phil with a 2012 Career Development Award. He is the incoming chair for the Canadian Clinical Trials Group (CCTG) Investigational New Drug (IND) Committee and the Clinical Director at the Princess Margaret Cancer Centre. He is a member of the Steering Committee for the American Association for Cancer Research (AACR) Genomics, Evidence, Neoplasia, Information, Exchange (GENIE) Project, and international data-sharing initiative that links cancer genomic data with clinical outcomes from tens of thousands of cancer patients treated at leading international institutions. His clinical practice includes the treatment of patients with breast and testicular cancers. His research involves early phase clinical trials with novel cancer drug treatments and the personalized treatment of cancer based upon the results of testing for DNA mutations within tumor cells. “The same boiling water that softens the potato, hardens the egg. It’s not about the circumstance, but what you’re made of.” - Unknown

Dr. Aaron Hansen Aaron is a staff medical oncologist in the Division of Medical Oncology and Hematology at the Princess Margaret Cancer Centre. He is an Assistant Professor of Medicine at the University of Toronto. He graduated from the University of Queensland Medical School and completed his Internal Medicine and Medical Oncology specialization in Australia. Following this, he undertook a fellowship in experimental therapeutics in the Bras Drug Development Program at the Princess Margaret Cancer Centre.

In 2013, Aaron was recognized by the Conquer Cancer Foundation of the American Society of Clinical Oncology (ASCO) with a Young Investigator Award. He is a member of the Endocrine Effects from Immunotherapy working group for the Investigational Drug Steering Committee (IDSC) of the National Cancer Institute (NCI). His area of interests are head and neck cancer and genitourinary malignancies. His research is focused on the development of new drugs with a particular interest in immunotherapy and understanding the toxicities of immunotherapy agents.

Dr. Albiruni Razak Dr. Razak is an Assistant Professor at the University of Toronto. He is also a Staff Medical Oncologist at the Princess Margaret Cancer Centre and Mount Sinai Hospital, where he leads the Medical Oncology Sarcoma Program. Originally from Malaysia, Albiruni completed his medical and basic oncology training in Ireland, winning the Holles Street Hospital Medal. Following this, he undertook higher oncology training in England and Canada, before being appointed to his current post. Albiruni has received several international awards, including the Young Investigator Award from the American Society of Clinical Oncology (ASCO) and the Mick Knighton Mesothelioma Award from the British Lung Foundation. His work in new drug development includes a special focus on methodology in early phase clinical trials. Albiruni disease-related focus is in the field of bone and soft tissue sarcomas.

Dr. Anna Spreafico Dr. Spreafico is an Assistant Professor at the University of Toronto and Staff Medical Oncologist in the Division of Medical Oncology and Hematology at the Princess Margaret Cancer Centre. She received her medical degree and oncology training in Milan, Italy. She obtained her PhD in translational research in the Program for Evaluation of Targeted Therapies at the University of Colorado and completed her training in experimental therapeutics with a fellowship in the Bras Drug Development Program at the Princess Margaret. She is the recipient of multiple international awards, including the Conquer Cancer Foundation of the American Society of Clinical Oncology (ASCO) Young Investigator Award. Anna is a member of the Phase l and Tumour Immunotherapy Programs at the Princess Margaret Cancer Centre. Her disease-specific interests are in melanoma/skin and head and neck cancers. Her research focuses on early phase clinical trials, including molecularly targeted and immune-oncology first-in-human and first-in-class agents. “My goal is to build a life I don’t need a vacation from.” Rob Hill Sr.

Greetings from Dr. Stephanie Lheureux I was born and raised in the north of France, did my initial training in Lille, a “chti” town situated along the border of France and Belgium. As the eldest child in a family involved in politics and agriculture, I learned from a young age the importance of contributing to one’s community and of helping others. It was this example set by family as well as my strong curiosity for how things work that directed me towards the field of medicine. After completing my medical studies and specialization in Medical Oncology from the University of Caen, I began my career as an Assistant Professor at the Academic Cancer Center of Caen in Normandy (France), where my practice combined research and clinical care in gynecologic cancers. I knew from my early days in medicine that I wanted to have my life’s work directed towards helping patients diagnosed and living with cancer. Cancer is a complex disease and I quickly realized as most clinicians do, that learning from the past is critical to changing the future and making a difference in patient outcomes. To further understand biology and develop new options for treatment, I continued my training and completed my PhD in gynecologic cancers and helped developed these findings into a clinical trial being run throughout France. I became very interested in learning how to bring lab findings to clinical testing more quickly and so my supervisor at the time suggested I meet Dr. Oza and the team in the Bras Drug Development Program. “They are a premier centre in early phase drug development and clinical trials, and home to an outstanding Clinical Research Fellowship Program”. Looking back, this was the beginning of a new journey that brought me, my husband and two kids to Toronto. I remember my first few weeks at Princess Margaret as a Clinical Research Fellow in the Bras Drug Development Program (DDP) and being in the Gynecology clinic with Dr. Oza. There was an energy in the air that was palpable as we sat down to review the clinic list with the team. There were clinical trial options available for patients who were newly diagnosed as well as for those patients whose disease was a bit more challenging to treat. At the time, I can remember reviewing the list of clinical trials enrolling patients onto study and being impressed by the options available that would otherwise not be. Several of the studies included testing next generation targeted agents like poly(ADP)-ribose inhibitors, or PARP inhibitors like olaparib, now approved for the use of ovarian cancer. While those first few weeks in the Bras Drug Development Program and the Princess Margaret Cancer Program felt overwhelming; over my first few months I quickly came to realize the close community at Princess Margaret and DDP. Over the last several years as a member of the Bras Drug Development Program family, I remain inspired by the outstanding physicians and researchers here who are working together to overcome this disease. Each day, we work together to design the next-generation of cutting-edge clinical trials that are helping us understand how cancer begins, grows and ultimately, how we can stop it. The dedication of our physicians, nurses and staff continues to be my driving motivation for changing how we understand this disease. Importantly, it is my patients that remain my inspiration and my daily reminder that better is a choice. Every day we must choose to do better, so that we ask better questions and ultimately, do better for our patients. This is what they deserve and what we are joined by as a community of researchers. Stephanie Lheureux MD, PhD Staff Physician, Division of Medical Oncology & Hematology Site Leader, Gynecology Oncology - Princess Margaret Cancer Centre Assistant Professor, Faculty of Medicine, University of Toronto Recruited July 2015 “Do human beings ever realize life while they live it?” Thorton Wilder’s play – “Our Town”.

Greetings from Dr. Phillipe Bedard In 2012 we launched the Integrated Molecular Profiling in Advanced Cancers Trial (IMPACT) and the Community Molecular Profiling in Advanced Cancers Trial (COMPACT). These studies enrolled more than 3,000 patients for the testing of DNA mutations across approximately 50 genes that are related to cancer. The preliminary results were recently published in the scientific journal GENOME MEDICINE. We demonstrated that this type of molecular profiling could be integrated in routine clinical care. Patients who were treated on clinical trials with new cancer drugs matched to their mutation profile or DNA, were more likely to experience shrinkage of their tumors than patients who were treated on clinical trials with drugs that were not matched to specific DNA mutations with their cancers. We also joined forces with seven other international cancer centres in a data-sharing initiative led by the American Association for Cancer Research (AACR) known as project GENIE (Genomics Evidence Neoplasia Information Exchange). GENIE is an international data-sharing initiative that allows us to share data that includes DNA mutation data and clinical outcomes from tens of thousands of cancer patients, to advance precision cancer medicine. We contributed data from 1,277 patients enrolled in the initial phase of the IMPACT and COMPACT trials to the first public release of data from project GENIE in January 2017. Building on the success of IMPACT and COMPACT, we developed and launched a new province-wide alliance known as the Ontario-wide Cancer Targeted Nucleic Acid Evaluation (OCTANE) study in 2016. OCTANE provides next generation sequencing (NGS)-based molecular profiling at five Ontario cancer centres: the Juravinski Cancer Centre, London Health Sciences Centres, The Ottawa Hospital, Kingston General Hospital, and the Princess Margaret Cancer Centre. OCTANE includes a common platform to visualize and share genomic and clinic data, in order to improve access to precision medicine clinical trials across the province and accelerate the development of novel “omic”-based tests for clinical use. Dr. Philippe Bedard, MD FRCP© Associate Professor of Medicine, University of Toronto Fellowship Director, Bras Drug Development Program Staff Medical Oncologist Princess Margaret Cancer Centre

“The more you praise and celebrate life, the more there is in life to celebrate.” Oprah Winfrey

NewsBytes Dr. Amit Oza, Director, Bras Drug Development Program After an international recruitment drive, Dr. Amit Oza has won the position of Head for the Division of Medical Oncology & Hematology at the Princess Margaret Cancer Centre. As one of the largest divisions affiliated with the University of Toronto, Amit will be responsible for working with more than 80 physicians dedicated to treating and researching blood and solid cancers at Princess Margaret. Congratulations Dr. Amit Oza!

PHASE ll and lll Drug Trials – BRAS Drug Development Program Within the Phase ll setting, Dr. Oza and the staff at the BRAS Drug Development Program has been involved in participating in key clinical trials examining the effect of PARP inhibitors – agents that take hold of vulnerabilities in DNA repair, which force cancer cell death, and have been approved for clinical use around the world, primarily in patients with mutations in BRCA1 or BRCA2 genes. This year, Amit was part of the international team that published findings from a large phase lll trial of Rucaparib, a PARP inhibitor, which showed efficacy in women with high grade serous ovarian cancer, regardless of whether they had BRCA1 or BRCA2 mutation. Findings from the study were published in the prestigious New England Journal of Medicine. Important new findings have become available for women with endometrial cancer in whom the disease has returned. Data analyzed from the large phase ll study led by Drs. Dhani and Oza from the BRAS DDP’s Princess Margaret Phase ll Consortium, show that the targeted agent Cabozantinib, designed to hone in and target specific pathways that allow cancer cells to ‘talk’ to one another, is well tolerated in patients with manageable side effects, and is effective at treating the disease. Over the past three years, more than 80 patients from across Canadian cancer centres and affiliate centres in the United States, participated in the study to show that in those women with endometriod endometrial cancer, partial responses were achieved, and there were also patients who experienced more than 12 weeks without any progression of the disease. That’s a common marker used by physicians in clinical trials indicating effect, and it’s an important finding for a group of patients who have run out of treatment options after standard of care. Additional studies are now underway to see whether specific mutations may also help identify those patients who may respond to treatment. Findings from this study are now part of a larger, international phase lll study, as well as another phase ll trial with an immune blocking agent.

Acetylsalicylic Acid – ASA – Aspirin In collaboration with the Canadian Cancer Trials Group (CCTG, formerly NCIC CTG), Dr. Amit Oza will be launching one of the first international chemo prevention studies in high grade serious ovarian cancer! The study is examining the impact of daily low-dose use of acetylsalicylic acid (ASA), most widely known as Aspirin, in women who are at a high risk for developing ovarian cancer; specifically those women who harbour a mutation in their BRCA1 or BRCA2 genes. With support from the Canadian Cancer Society Research Institute, the study will launch in several international jurisdictions, including Australia, Israel and the United Kingdom!

Phase l: First-in-Class and First-in-Human Studies “The Bras Drug Development Phase l Program has been instrumental in providing data from first-in-class and first-in-human studies that has laid the foundation for the subsequent development of many anti-cancer agents, some of which are now considered the standard of care in several cancer types. This is a strong clinical translational program that has had a major influence on early phase clinical trials in Canada and trained many leaders.”

BRAS DDP trains drug development physicians of the future What Is A Fellow? “Fellows from all over the world travel to Princess Margaret to learn the business of drug development – especially Phase l development, so that they can go home and build their own teams. Phil – Dr. Bedard, who runs our fellowships, has a huge job because this is such an important aspect of what we do,” Dr. Siu explains. “We’re actually training the scientists who will go on to become our partners all over the world. It’s like they’re seeds that grow into trees that are growing seeds again.” “In addition to this, through our fellowships, we’re actually growing the global capacity for first-in-human trials,” Lillian explains. “Very few programs in Phase l do this.” “Dr. Bedard and the Principal Investigators hold weekly meetings with their fellows to go through performance feedback. Fellows, after all, are on the front line: they get exposed to every trial and they see one another’s patients. This is the very best way to learn how to be observant, how to recognize patterns, how to put it all together and tell a story,” Lillian says. “We absolutely stand alongside them. But we let them tell us their story and we provide feedback.” Dr. Lillian Siu, MD, FRCPC - Director, Phase l Program

Amy Prawira – Indonesia and Australia BRAS DDP Clinical Fellow 2015 - 2017

WHERE IS HOME? This is a question that I always find hardest to answer. I am very fortunate to have had the opportunity to live and work in a number of different places in my life. I was born in Indonesia and spent my childhood there before moving to Singapore to complete the final years of my secondary education. I graduated medical school and completed internal medicine training in Melbourne, Australia before moving to Newcastle – also in Australia – to complete my medical oncology training. As part of my medical and specialty training, I have had the chance to live and work in a few rural and regional Australian towns including Horsham, Mount Beauty, Warnambool, Geelong, Sale and Tamworth. And then I came to Toronto! Thanks to family, good friends and colleagues, I have felt at home in all the places that I have been. So my definition of home is a place where I can live and work with people I care for, who also care for me in return. WHY ONCOLOGY? The most rewarding aspect of my medical career is my interactions with my patients. I think it is a true privilege that, as medical oncologists, we get to be there through what is most often the most difficult times in our patients’ and their families’ lives. My patients and their families have shown me how the human spirit can triumph through the most trying of times. This gives me the hope and encouragement that together, we will, and we have to, find ways to cure cancer. WHAT ARE YOUR MAIN AREAS OF INTEREST? My main areas of interest are head and neck cancer and Phase l clinical trials. Head and neck cancer patients strike me as particularly stoic, given how disabling the disease is and how tough the treatment is. We treat the majority of patients with curative intent, but the disease relapse rate is unacceptably high. I think molecularly it is a fascinating disease. There remain a lot of unanswered questions, and a lot of room for improvement, especially from the systemic treatment point of view. Many times since starting my medical oncology training, I have been seated across patients with incurable cancer, explaining to them that we have no further treatment options to offer. Even though there are currently many exciting developments in medical oncology, for this one patient, we are not moving fast enough. I share my patients’ sense of desperation. My undergraduate research thesis was in the preclinical development of a novel therapeutic agent for glioblastoma multiforme. The prostate cancer arm of the drug went on to Phase l clinical trial. I find the science behind this very intriguing, and I wanted to investigate what makes a drug work, what makes them fail, and what can we do to make them both effective and safe to administer to patients. WHY DID YOU CHOOSE TO COME TO THE BRAS DRUG DEVELOPMENT PROGRAM? It was my mentor, Dr. Stephen Ackland in Australia who suggested I apply for a fellowship with Dr. Lillian Siu. He knew that I was interested in Phase l clinical trials and head and neck cancers, and advised that I go to learn from the best! The Princess Margaret Cancer Centre’s BRAS Drug Development Program is one of the world leaders in early phase clinical trials. They are at the helm of development of new oncological therapeutics. During my first visit here, the passion is almost palpable. Certainly this has proved the case the whole time I have been here.

“Over 180 languages and dialects are spoken in Toronto.” - Unknown

WHAT ARE SOME OF THE DISTINCTIVE QUALITIES OF THE PRINCESS MARGARET CANCER CENTRE? At the Princess Margaret, I find that the staff not only strives to provide excellent medical care, but they also work with a sense of hope. I think this comes from the passion with which the staff here, in particular my mentors, conduct their research. They are looking after not only the current patients, but also patients of the future. This hope keeps us going, and I think it is because they are doing this for the right reasons, that the Princess Margaret is one of the top cancer centers in the world! They are doing this for the patients. There is a long-standing culture of nurturing young oncologists here at the Princess Margaret. Fellows have the opportunity to be involved in all manners of research: retrospective, reviews, systematic reviews or meta-analyses, and prospective clinical trials. From the research point of view, my mentors have taught me to ask the right questions, design the right trials and make sure it is safe and always in the patients’ best interest, and carry it out to the end. This applies to trials that are both sponsored by industry and initiated by investigators. This level of dedication to teaching and mentoring is absolutely invaluable, and is very difficult to find indeed. WHERE DO YOU THINK WE ARE GOING? In the past decade we are making strides in improving our understanding of the molecular basis of cancer. In some cancers, we are now breaking out of the blanket treatment approach and moving towards individualized treatment. While, for some patients we have achieved great outcomes, even long-term disease control, there remains a lot of work to be done to increase the number of people who would benefit from treatment, while minimizing toxicities and futile treatment. The human body is an ecosystem of processes with important and constant interactions among all its parts.. By adopting a more integrative approach to include all aspects of medical science: such as genetics, epigenetics, proteomics, metabolomics, we can make it all come together. With an increased understanding of the scientific basis of cancer, we would no longer compartmentalize our efforts, but would operate in a more “holistic” way. WHAT HAVE YOU FOUND MOST REWARDING ABOUT YOUR FELLOWSHIP? Learning from and working with my mentors is one of the most rewarding aspects of my fellowship. In medicine, patients always have to come first. Without the right approach, the long hours that we put into working, studying and caring for our patients, can really take a toll. My mentors, therefore, have been absolutely essential in shaping me into the oncologist that I am today. I have absolutely enjoyed looking after my Canadian patients, increasing my clinical and translational research experience and know-how, and getting to know all the staff and other fellows from all over the world. It truly has been a fantastic few years. WHEN WILL YOU RETURN HOME? I am completing my fellowship on May 1, 2017 to continue my work in Sydney, Australia. My work and research focus will continue to be head and neck cancers and early drug development. It is very sad to leave the fantastic team here at the Princess Margaret, who have really made me feel at home. I hope to continue the collaboration and friendship that have been developed here.

“A long life may not be good enough, but a good life is long enough.” Anonymous

Ilaria Colombo - Italy BRAS DDP Clinical Fellow 2016 - 2018

I was born in Lecco, in the north of Italy. I obtained my medical degree at Milan-Biocca University and completed my training in oncology in the same University. I then practiced as a medical oncologist at Lecco Hospital, with a special interest in gynecological and breast cancer. In 2016 I moved to Toronto with my husband and started a Fellowship in Gynecology in the Bras Drug Development Program at the Princess Margaret Cancer Centre. WHY THE PRINCESS MARGARET CANCER CENTRE? Princess Margaret is a worldwide recognized cancer centre where it’s possible to combine clinical and research activity with providing excellent care to cancer patients. The Princess Margaret is one of the most advanced centres for the management of gynecological cancers. It features collaboration between preclinical and clinical infrastructures. My fellowship here is giving me an inestimable opportunity to increase my expertise and expand my knowledge at one of the best cancer centres in the world! WHY DID YOU TAKE UP MEDICINE? I have always been fascinated by the complexity of the human body. Since I was a child, science was one of my favourite subjects and my interest increased in high school. I have always been interested in helping others, so when I was a teenager, I joined volunteer programs in my community. The decision to apply for Medicine came naturally to me during my last year of high school. Being a doctor was the perfect way to combine my interest in science with my wish to be useful to others. WHY ONCOLOGY? I choose oncology for two main reasons: First of all, I have always been very interested in the complex biology of cancer cells, and inspired by the extensive research still required to understand how and why cancer cells proliferate and disseminate. Oncology is a dynamic field that is rapidly expanding. There are so many new discoveries that require continued update and study. I really love the challenge. The second reason I chose to be an oncologist is the relationships I develop with my patients. In our profession, we see the patient many times and this continuity gives us the opportunity to build a strong relationship based on trust and compassion. You can really feel that you are with them in both the good and the bad moments. You celebrate each victory with them and you offer them your support and your presence in the hardest moments leading up to the end. Despite the enormous improvement achieved in the past decade, there is still so much to do to improve the care of our patients, and this is the engine that gives me the strength to carry on with my job, and the motivation to improve my knowledge every day. WHAT IS YOUR ROLE AS A FELLOW AT THE BRAS DRUG DEVELOPMENT PROGRAM? As a clinical research fellow in the Bras Drug Development Program, my activity is both clinical and research. My main focus is gynecological cancers. I take part in the daily clinical activity under the supervision of Drs. Oza and L’heureux. I follow patients who are enrolled in clinical trials. I help in the management of new patients who have been admitted to the ward. This fellowship is also providing me with remarkable experience in clinical research. My mentors have given me the opportunity to have an active role in the different steps required for the development of new drugs: the creation of clinical trials, their design, the development of protocols, the enrolment, the analysis of data and the patients’ follow-up. Right now, a major focus on oncology is on immunotherapy. It’s well established in some cancers, like melanoma and lung, but in gynecological malignancies, there is still a lot of work to be done to understand how to use immunotherapy in this cancer subtype. I am responsible for some studies that are trying to answer this question. Moreover, I am developing two research projects focused on molecular and immune profiling of gynecological cancers in collaboration with scientists from different fields. The opportunity to join translational research projects is amazing and it makes me feel that I am contributing to the improvement of oncology knowledge. The BRAS Drug Development at Princess Margaret is an outstanding program and I am very honoured to be part of it. “A word of encouragement during a failure is worth more than an hour of praise after success.” - Unknown.

WHO ARE YOUR MENTORS AT THE BRAS DRUG DEVELOPMENT PROGRAM? My mentors are Drs. Oza and L’heureux. They have unremarkable clinical and research expertise, and I have learnt so much from them in my first year of fellowship. I am so grateful to them for giving me the opportunity to be here and to be part of their team. WHAT DO YOU THINK ARE SOME OF THE MAJOR ADVANCES WE HAVE HAD THE LAST FEW YEARS IN CANCER RESEARCH? There have been a lot of advances in the field of oncology in the last decade. We have a better understanding of the molecular mechanism that may drive the development of cancer, its progression, diffusion and its resistance to treatment. Nowadays, it’s easier and faster to study the DNA of cancer cells and this is key to the development of new treatments. For that reason, the collaboration between scientists and clinicians is necessary to improve the cure of cancer. Different targeted therapies that inhibit specific mechanisms that keep cancer cells alive, have been developed and approved in the past few years and have improved the prognosis of cancer patients. Immunotherapy is an emerging field that instead of killing the cancer cells as chemotherapy does, it helps to stimulate our immune system to fight the cancer. In the past few years, different immune agents have been tested and important results achieved. However, not all the patients benefit from this treatment and more research is needed to understand the mechanism of resistance. Another important victory has been the identification of altered DNA that increases the risk of developing cancer such as the BRCA 1 – 2 genes. When a person carries this mutation, the risk of developing breast and ovarian cancer is very high. Knowing that one is a carrier, opens the door to preventative measures such as joining specific screening programs, or undergoing prophylactic surgery when indicated. WHAT MAKES THE PRINCESS MARGARET CANCER CENTRE AND THE BRAS DRUG DEVELOPMENT PROGRAM ONE OF THE TOP FIVE IN THE WORLD? The Princess Margaret Cancer Centre is a great place to learn and work. There are fellows and staff coming from all over the world. And there are good reasons for that. Our patients have access to the most up-to-date treatment programs and drug trials. Even though the research is the main focus, the patient is always at the center of care. I have met so many good people who work here. They strongly believe in what they do, you can feel it in the air; their motivation, enthusiasm and their desire to do better for the patients is the precious common value of all the people who work here. This inspires me every day! WHAT INSPIRES YOU? The patients are my true inspiration, along with the people who work here. The wish to improve the treatment of cancer, to give hope to my patients and their families, to help them when there is no possibility of a definitive cure, to help improve their quality of life and to be part of the progress they achieve. This is what inspires me! YOU HAVE ENTHUSIASM AND A PASSION FOR YOUR JOB. I really think that it is impossible to do this job without true passion. It requires a lot of sacrifice, many hours spent in the hospital. You often have to use your own time to carry on your research projects. I am so far from my country, my family and friends, that without that passion, this would be very difficult for me. But the possibility of working with internationally recognized leaders, and to learn from them, makes up for all the difficulties. In the BRAS Drug Development Program., I have the opportunity to know other fellows from all over the world, and to share their experiences and expertise. ARE YOU GOING BACK TO YOUR HOME COUNTRY AFTER YOUR TWO YEARS ARE UP? I don’t know yet what I will do and where I will go after I complete my fellowship. I quit my job in Italy to come here, so I do not have a position there now. But I do have my family and friends. So, I would like to say – yes I will go back to Italy. I’m a little bit homesick! However, I really like the type of job that combines clinical and research activity. This type of job is more difficult in my country where there are fewer resources than here at Princess Margaret. So, I do not have an answer yet. HOW DO YOU LIKE TORONTO? There are things that I like and others that I like less. It is a very big city and I wasn’t used to that. In Italy, I lived in a little town: no noise, no traffic, easy to get in touch with people, lots of nature. On the other hand, in a big city you have a lot of opportunities and there’s always something to do – restaurants, cinema, theatre, games. As soon as spring begins, my husband and I will enjoy the outdoor activities in Ontario’s awesome parks. Lots of them are very close to the city and you have plenty of choices, from trekking to canoeing, from cycling to camping.

“Don’t raise your voice, improve your argument.” – Desmond Tutu

Victoria Mandilaras – Montreal, Canada BRAS DDP Clinical Fellow 2015 - 2017

WHAT BROUGHT YOU TO THE PRINCESS MARGARET CANCER CENTRE? One of my mentors at McGill, was Dr. Jeremy Sturgeon. He had trained and worked on staff at Princess Margaret until 2006 when he left to take on the position of the Chief of the Medical Oncology Department at the McGill University Health Centre. We had worked together in the gynecologic oncology clinics and he sparked in me a special interest in this subspecialty. He said: “If you want to learn about gynecological cancers, you MUST go to Princess Margaret.” He put me into touch with Dr. Amit Oza and the rest is history… WHY DID YOU WISH TO BECOME A DOCTOR? Growing up, I was naturally inclined towards the sciences. I liked things that were logical and explained how things worked. I knew I wanted to do something that could incorporate this interest, but I also wanted to interact with people rather than sitting behind a bench or desk all day. Medicine was the perfect way of combining the two. WHAT IS YOUR WORK OF EXPERTISE? My practice focuses mostly on the treatment of gynecological cancers but not many people know that I treat tumours of the central nervous system as well (I keep that part low key). DO YOU TREAT EACH SITE DIFFERENTLY? Brain tumours and gynecological cancers are fundamentally quite different in terms of their treatments but are both devastating diseases for patients and their families. Although treatment algorithms are different, better treatments are desperately needed. The common thread for both these sites is that there is a huge amount of cutting-edge research being generated for both of them. It’s in exciting time to be practicing in either field. DO YOU FEEL WE ARE MAKING PROGRESS IN THE WAR AGAINST CANCER? I do, and I don’t just say that because I’m an oncologist. We’re learning more about tumours beyond the anatomical site from which they stem. No two ovarian cancers are the same, for instance. As close as even 10 years ago we lumped the treatment of all of them together. That’s wrong and now we understand that. Things like molecular profiling have changed the field, enabling us to be more precise in our treatments and tailoring them to the patient and not the tumour. Now we’re adding even more complexities to this like epigenetic assessment and the patient’s immunologic landscape. WHAT IS IMMUNOTHERAPY? Immunotherapy is a therapy that makes use of the patient’s own immune system to fight their cancer. This may be a vaccine therapy where you stimulate the immune system to recognize a part of the tumour, or an antibody therapy where you activate the immune system in hopes that it will recognize cancer in the body as an intruder and target it. It has revolutionized the treatment of lung cancer and melanoma among others. It is in the very early stages of development in gynecological cancers and brain tumours but hopefully will have a large impact as well.

“To live is the rarest thing in the world. Most people exist, that is all.” - Oscar Wilde

IS THERE ANY INTERACTION WITH OTHER MAJOR CANCER CENTRES IN THE WORLD? Princess Margaret is part of the Princess Margaret Consortium made up of other cancer centres in Canada and we collaborate in early phase clinical trials with other large centres in the United States. As part of Bras Drug Development Program, I’m exposed to many trials that are led by these consortia. Of course, there are also collaborations around the world with regards to recruiting patients, but also for collaborating on research within the realm of these studies. We have studies that involve sending out tissue collected from patients on study, to laboratories across the world to make use of an expertise that only they may have for the purpose of advancing this science. THE POPULATION OF ANY ONE TRIAL GLOBALLY IS QUITE LARGE? The trials range in size from a cohort of 50 patients up to thousands depending on the stage of drug development. Newer drugs are tested in smaller cohorts to make sure they are safe and effective before moving on to larger confirmatory trials. These smaller trials are often offered to patients where treatment options are limited and may offer new options where standard therapies are lacking. WHAT ARE SOME OF THE MAJOR ADVANCES IN THE LAST FEW YEARS, AND CHALLENGES? We have redefined cancer on a genetic level. For example: The changes we find in the tumour DNA which may have helped the cancer to grow, versus where in the body the cancer originally developed, has definitely advanced the field. This has enabled more precise treatments. For instance - the treatment of ovarian cancer with a mutation in the BRCA gene with a class of drugs called PARP inhibitors. These drugs exploit the deficits in the cancer cells caused by the BRCA mutation which causes them to die. The challenges remain further defining these mutations. The knowledge we have now is only the tip of the iceberg. ARE WE SEEING NEWER CANCERS? In a way, yes. Again because we are becoming so much more precise with the way we classify these cancers based on their genetics which we are starting to group into smaller and smaller categories. These categories may have an impact on the way we treat the cancers within each one. WHAT IS GREAT ABOUT WORKING IN THE BRAS DRUG DEVELOPMENT PROGRAM AT THE PRINCESS MARGARET CANCER CENTRE? The Bras Drug Development Program is definitely unique in that it’s a well-oiled machine. It’s made up of a large number of individuals who each play an integral part. As a fellow, I’ve always felt well supported and I have the resources to be successful in my research. During my time here, I’ve been able to develop protocols and see them to fruition because of the resources at my disposal. WHAT INSPIRES YOU TO CONTINUE ON IN YOUR WORK? My patients inspire me. My interactions with them, getting to know them on a personal level and being a part of their story is what encourages me to continue the work that I do. I can’t cure them all but I can help them to the best of my abilities. WHAT ARE YOU GOING TO BE DOING AT THE END OF YOUR TWO YEARS? At the end of my two years, I’ll return to work in my home city of Montreal, Canada. I will also start my MBA degree, as if I did not have enough training! I’ll be moving on to my next interest of determining how to best administer healthcare in the future within the economic constraints we face in the public healthcare system, and the ever-increasing cost of cancer care. I will keep my ties with Princess Margaret, however, and look forward to collaborating in the future.

“An invisible thread connects those who are destined to meet, regardless of time, place, or cirumstance. The thread may scratch or tangle, but it will never break.” – Ancient Chinese Belief

Daphne Dai – Australia BRAS DDP Clinical Fellow 2015 - Present

WHAT IS A FELLOW? In the medical field, a Fellow is a doctor who has completed or is at the final stages of completing specialty training, and is undertaking additional subspecialty training. In the case of the Bras Drug Development Fellows, we are all qualified medical oncologists, coming together from all over the world (Italy, Israel, Burma, Australia, Jordan and Canada) to learn about the research and development of new cancer drugs in early phase clinical trials, typically over a one to two-year period. With supervision and mentorship from the staff, we are involved in the daily care of patients. Alongside clinical experiences, we also each have research projects in our areas of interest. WHY DID YOU BECOME A MEDICAL DOCTOR? I have wanted to be a doctor for as long as I can remember – probably since primary school. I love working with and relating to people, as well as solving problems and science. I also wanted to work in a field where I can be of service to the community. These were the main reasons behind my motivation to pursue medicine. I still remember the feeling I had when I learnt I got into Medicine at the end of high school. I was over the moon and very very grateful! WHY DID YOU CHOOSE ONCOLOGY? I get asked this question a lot when I meet people and I always fumble for an answer. Oncology was my first clinical rotation as a medical student and I decided then it was the specialty for me. I think there are several aspects that attract me to this field. Firstly, it’s an area of need. Secondly and probably most importantly, it’s the human side of oncology. While it’s challenging, it is also incredibly rewarding. Lastly, the science of cancer is fascinating. It’s also a very exciting time to work in this field as scientific discoveries are moving at an extraordinary pace. WHERE IS HOME? I’m from Melbourne, a coastal city in the south-eastern part of Australia. It’s the second largest city, otherwise known as the dining, coffee, sport and shopping capital of Australia (but I’m biased). WHAT HAS INSPIRED YOU SINCE YOU’VE BEEN HERE? What inspires me are the people I work with every day - the patients and my colleagues. Patients and their families, who despite what they’re going through, constantly amaze me with their strength, grace and kindness. They teach me perspective and humility. Teamwork is a major factor behind the success of the Bras Drug Development Program and Princess Margaret. My colleagues scientists, nurses, doctors, pharmacists, allied health staff, coordinators and administrative staff - are dedicated to and passionate about their work. We may have differences in opinion at times, but we all have a common goal. We frequently come early, stay behind and work on weekends, because we believe in what we do. WHAT IS PERSONALIZED CANCER MEDICINE? I think medicine has always been personalized in a way. We have treatment algorithms and guidelines, but good clinicians will tailor treatments to suit their patients’ individual circumstances and wishes. More recently, technologies (for example, by looking at tumor DNA) are allowing us to learn more about how cancers form and evolve over time and in response to treatment. We are also learning about how the molecular makeup of each patient’s cancer is unique and as such may be vulnerable to different treatment strategies. The hope of truly personalized medicine is that we will be able to tailor treatments to each patient (down to the genomic and molecular level), thus potentially improving the chances of success and minimizing side “Listen and Silent are spelled with the same letters.” - Anonymous

effects. However, while there have been some major advances, we’re only at the beginning of uncovering the complexities of cancer and how best to address these therapeutically. WHAT ARE SOME OF THE ADVANTAGES OF BEING A BRAS DDP FELLOW? The BRAS Drug Development Program has an international reputation, not only as a leading phase I program, but also for its excellent fellowship program. I feel very fortunate to have had a wonderful experience over the last two years. It’s a very hands-on fellowship. We are exposed to all aspects of drug development, including assessing patients, managing side effects, writing trial protocols and working with sponsors. Our mentors also make sure we have opportunities to develop and work on our own projects. Despite working hard and often feeling out of my depth, I’ve never felt unsupported or alone. Another huge advantage is being able to meet and work with other fellows from around the world. I’m confident many will become life-long colleagues and friends. On a personal note, it’s been wonderful and eye-opening to live in Toronto. My husband and I have both fallen in love with this multi-cultural and dynamic city. WHAT ARE ‘PHASES’? HOW MANY ARE THERE? Testing of new drugs occurs in sequential stages, or ‘phases’. The preclinical phase refers to research done by scientists in the laboratory in human cells or animal models. When new drugs have shown promise in the laboratory, they might move on to Phase I testing or ‘first-in-human’ trials, which is a main focus of the BRAS Drug Development Program. The main purpose of a phase I trial is to see if a new drug or new combination of drugs is safe in humans. If this is proven, then a drug may get taken forward to Phase II and III trials, where we’re looking at whether it is effective or not and how it compares with the current standard therapy. Depending on these results, regulatory authorities will make a decision about whether the drug will be approved, licensed and made available to patients. Phase IV research refers to the post-marketing study of drug safety and effects, including long-term effects. Generally, as we progress from phase I to IV trials, greater numbers of patients are involved. Drugs that are unsuccessful in early phase testing (unfortunately the majority) will not enter late phase development. HOW LONG DOES THIS PROCESS TAKE STARTING AT PHASE l AND ENDING AT PHASE lll? This can vary depending on multiple factors and there’s no standard time. Previous research showed that the time period averaged 7-9 years from first-in-human trials to regulatory approval for oncology drugs. More recently, drugs which have shown convincing efficacy early on in the development process, such as targeted drugs and immunotherapy drugs, have been approved in much shorter timeframes. WHAT ARE THE ADVANTAGES OF BEING A PARTICIPANT IN A PHASE l TRIAL? Clinical trials offer patients more options and access to novel treatments beyond the standard therapies that are available to them. If patients join a Phase I trial at Princess Margaret, the phase I team including staff, fellows and nurses will take over their oncological care, which means patients will have the benefit of and access to a dedicated around-the-clock clinical team. Many patients are also motivated to participate in early phase trials to contribute to science and to benefit others, which is tremendously generous and altruistic. THERE IS A BIG BANNER OUTSIDE THIS HOSPITAL: “WE WILL CONQUER CANCER IN OUR LIFETIME.” IN YOUR LIFETIME, DO YOU BELIEVE THIS WILL HAPPEN? A similar banner caught my eye when I came to interview in 2013. At the time I thought it was ambitious, but also bold and full of hope. The field of cancer medicine is moving rapidly with innovations and breakthroughs happening all the time. So much progress has occurred, even just in the last few years. In my lifetime, I have no doubt we will be able to prevent, control and treat cancer much more effectively, using safer and ideally individualized treatments, such that patients will be able to live longer and better. WHEN YOUR FELLOWSHIP IS FINISHED, WHERE ARE YOU GOING AND TO DO WHAT? I don’t have concrete plans yet. The opportunities in medicine are so vast, so who knows! My hope is to combine clinical work with research in my future role. The experiences and the knowledge I have gained working at the Bras Drug Development Program has had a huge impact on me and will always stay with me. I also hope to establish future collaborations with my colleagues and mentors here.

“I am not afraid of storms for I am learning how to sail my ship.” Louisa May Alcott

Physician Leaders in Drug Development of the Future – Current Dr. Amy Prawira – Indonesia, February, 2015. Dr. Daniel Shepshelovich – Israel, September, 2016 Dr. Daphne Dai – Australia, April, 2015 Dr. Jeremy Lewin – Australia, September, 2014 Dr. Kyaw Aung – Myanmar, September, 2014 Dr. Samer Salah – Jordan, July, 2015 Dr. Yada Kanjanapan – Australia, April, 2016 Dr. Yeh Chen Lee – Australia, April, 2016 Dr. Ilaria Colombo – Italy, April, 2016 Dr. Victoria Mandilaras – Montreal, Canada, June, 2015 Dr. Sunu Cyriac – India, September, 2016 Dr. Luisa Bonilla – Israel, September, 2016

“Always remember if you get on the wrong train, you don’t have to ride it to the end of the line.” Station Master - Union Station, Toronto, ON.

Former BRAS DDP Fellows Herbert Loong – Hong Kong; Assistant Professor, Princess of Wales Hospital, HK Bridgette Ma – Hong Kong; Director Phase l program, Princess of Wales Hospital, HK Carol Townsley – Canada; Medical Director: After Cancer Treatment Transition Clinic, Women’s College Hospital, Toronto, CA Srikala Sridhar – Canada; Associate Professor, Princess Margaret Cancer Centre, Toronto, CA Mark Agulnik – Quebec, Canada; Associate Professor, Northwestern University, Chicago, US Ignacio Duran – Spain; GU Site Leader, Hospital Universitario Virgen del Rocio, Seville, ES Patricia Tang – Alberta, Canada; Associate Professor, Tom Baker Cancer Centre, Calgary, CA Steven Welch – Ontario, Canada; Associate Professor, London Health Sciences Centre, London, CA Christine Elser – Germany; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Laura Vidal – Spain; Medical Director, INC Research Christopohe Le Tourneau – France; Head, Phase l Unit, Institut Curie, Paris, FR Neesha Dhani – Ontario, Canada; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Hui Gan – Australia; Head, Phase l Unit, Ludwig Institute of Cancer Research, Melbourne, AU Anastasios Stathis – Greece; Attending Physician Clinical Research Unit, Oncology Institute of Southern Switzerland, Bellinzona, CH Benoit You – France; Head, Phase l Unit, Centre Hospitalier Lyon Sud, Lyon, FR Linda Lee – Ontario, Canada; Assistant Professor, McMaster University – Niagara Campus, St. Catherines, CA Alberto Ocana – Spain; Medical Director Translational Research Unit, Albacete University Hospital, Albacete, ES Daniel Renouf – British Columbia, Canada; Assistant Professor, B.C. Cancer Agency, Vancouver, CA Albiruni Razak – Malaysia; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Vincent Castonguay – Quebec, Canada; Assistant Professor, Laval University, Quebec City, CA Nicole Chau – Ontario, Canada; Instructor, Dana Farber Cancer Institute, Boston, US Ivan Diaz-Padilla – Spain; Sr. Medical Scientific Expert, Novartis Pharma AG, Basel, CH Ben Tran – Australia; Consultant Medical Oncologist, Royal Melbourne Hospital, Melbourne, AU David Cescon – Ontario, Canada; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Arif Manji – Ontario, Canada; Assistant Professor, The Hospital for Sick Children, Toronto, CA Solmaz Sahebjam – Iran; Assistant Professor, H. Lee Moffitt Cancer Center, Tampa, US Irene Brana – Spain; Assistant Professor, Vali D’Hebron Hospital, Barcelona, ES David Tan – Singapore; Consultant Medical Oncologist, National University Cancer Institute, SG Donna Graham – Ireland; Clinical Research Fellow, Queen’s Belfast University, Northern Ireland, IE Aaron Hansen – Australia; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Anna Spreafico – Italy; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Tom (Wei-Wu) Chen – Taiwan; Assistant Professor, National Taiwan University Hospital, Taipei, TW Joanne Chiu – Hong Kong; Assistant Professor, University of Hong Kong, HK Natalie Cook – United Kingdom; Consultant Medical Oncologist, University of Manchester, Manchester, UK Neda Stjepanovic – Serbia; Staff Medical Oncologist, Vall D’Hebron Hospital, Barcelona, ES Rossanna Pezo – United States; Staff Medical Oncologist, Sunnybrook Odetta Cancer Centre, Toronto, CA Sara Taylor – Ontario, Canada; Assistant Professor, British Columbia Cancer Agency - Centre for Southern Interior, Kelowna, CA Victor Rodriguez-Freixinos – Spain; Staff Medical Oncologist, Vall D’Hebron Institute of Oncology, Barcelona, ES Michelle Wilson – Melbourne; Staff Medical Oncologist, The University of Auckland, NZ Cristina Martin-Lorente – Spain; Staff Medical Oncologist, Barcelona, ES Stephanie Lheureux – France; Assistant Professor, Princess Margaret Cancer Centre, Toronto, CA Daliah Tsoref – Israel; Staff Medical Oncologist, Davidoff Centre, IL “The past is behind, learn from it. The future is ahead, prepare for it. The present is here, live it.” – Thomas Monson

Greetings from Paul Alofs The Princess Margaret Cancer Foundation is honoured to support the BRAS Drug Development Program’s Phase l clinical trials at the Princess Margaret Cancer Centre. The expertise in this area under the leadership of Drs. Philippe Bedard, Lillian Siu, Albiruni Razak, Anna Spreafico and Aaron Hansen, and their Phase l team of 45, demonstrates one of the many reasons the Princess Margaret Cancer Centre is one of the top 5 cancer research centres in the world. With over 20% of our active patient population on a clinical trial (vs. approximately 5% in other major U.S. cancer centres), the Princess Margaret Cancer Foundation and its donors, see a demonstrable and significant impact from the philanthropic funding of this very important program. With the completion of the foundation’s Billion Dollar Challenge this past January, we are now in the early days of delivering on our promise of Personalized Cancer Medicine. The landscape in cancer diagnosis and treatment is advancing rapidly, and this would not be possible without the generous support of our community. Our vision is clear, and like you, we are passionate about our goal: To Conquer Cancer in Our Lifetime. Paul Alofs President and CEO The Princess Margaret Cancer Foundation

“The world is round and the place which may seem like the end, may be only the beginning.” – Ivy Baker Priest

Princess Margaret Cancer Centre, Toronto, Canada

Lee Pettersen

September 13th, 1947 - May 2nd, 2017

Dear Friends, In 2008, I joined the Ride to Conquer Cancer in the inaugural year to support a friend who was diagnosed with a brain tumour. Little did I know as I peddled from Toronto to Niagara on my beloved blue Trek bike that less than one year later, I would be riding for myself. It marked the start of a journey for me, one with many highs and lows; a journey that family, friends, doctors, nurses and volunteers have been with me on for more than eight years. During that time, I participated in the Ride to Conquer Cancer every year--7 of which I was undergoing chemotherapy-- sporting my yellow survivor flag proudly as I learned the moment I walked in the doors at Princess Margaret, there’s no such thing as not having hope. With the help of an incredibly supportive team, family members and my partner Gord, I was able to ride alongside him and my two daughters, Kate and Ali, for my final ride in 2015. Words cannot describe the feeling of crossing that finish line with all three of them beside me, surrounded by fellow fighters and the people who make a future without cancer possible. We had all planned to be together with the team again this year to celebrate the 10th year of this outstanding event, but sadly my health has deteriorated and I am no longer able to train, much less participate. As I take a moment to reflect on the wonderful people I’ve met, and the incredible care I’ve received at the Princess Margaret Cancer Centre, I can’t help but think they are the reason I was able to be there year after year, as a fundraiser and participant. After major surgery, gold standard treatment and clinical trial after clinical trial, the terrifying truth is my options have run out, so I am asking my loyal supporters to forward their donations to a very worthy cause. The Bras Drug Development Program, at the Princess Margaret Cancer Centre where I have received my clinical trials, has created a position called “Nurse Navigator” on my behalf and named in my honour; a position created to establish a liaison with patients. The Nurse Navigator will work with the team acting as a bridge between clinical trials and personalized medicine. The Nurse Navigator will be vital in helping patients with complex care issues as well as coordination of their care The overall goal is to help patients sustain their sense of well-being through very difficult transition periods. I would be thrilled if you would support this position. When I shifted from a clinical trial that required weekly visits to chemotherapy I was devastated and scared of the unknown; I was worried about not seeing my health care team so frequently. I imagine many other cancer patients who experience similar transition points in their care may feel abandoned, adrift and isolated, but for me, at a time I was feeling quite vulnerable, my former clinical trial nurse made it her mission to keep checking in on me, my unofficial nurse navigator! I cannot begin to describe how much that meant to me. I’ll be forever grateful. I ask you from the bottom of my heart, to please consider making a donation to support the development of the Nurse Navigator role, as I couldn’t think of a more worthy cause. Lee As of July 7, 2017, the late Lee Pettersen’s fund has raised an incredible $59,900 for the Nurse Navigator position named in her honour! “Nothing can dim the light which shines from within.” – Maya Angelou

Phase I Members of the Phase I Program gratefully acknowledge the support of Bras Drug Development Program BMO Financial Group Canadian Cancer Trials Group Cancer Care Ontario Applied Cancer Reseach Unit Grant Melissa Katzman Education Fund Ontario Institute for Cancer Research Research Fellowship Fund Princess Margaret Cancer Foundation U.S. National Cancer Institute

For more information about industry partnership or to set up a trial, please contact: Dr. Lillian Siu Princess Margaret Cancer Centre 700 University Avenue 7-624 Toronto, Ontario, Canada M5G 1Z5 T +1.416.946.2911 F +1.416.946.4467 E lillian.siu@uhn.ca

If you would like to support the BRAS DDP, please visit: www.thepmcf.ca/bras For more information on the BRAS DDP, please visit www.BRASddp.com For more information on The Princess Margaret Cancer Foundation, please contact: Cindy Goelman E cindy.goelman@thepmcf.ca T +1.416.946.4481 610 University Avenue Toronto, Ontario, Canada M5G 2M9

If you wish to be on our mailing list, please contact Maggie Bras at maggiebras@gmail.com

MISSION STATEMENT Exciting breakthroughs in the understanding of cancer biology continue to identify new approaches to cancer therapy. The goal of The Robert & Maggie Bras and Family New Drug Development Program at Princess Margaret Hospital is to identify new approaches to cancer therapy, for the treatment, management and eradication of this disease. ESTABLISHMENT The Princess Margaret Hospital Foundation (The “Foundation�) hereby agrees to establish The Robert & Maggie Bras and Family New Drug Development Program Fund (the fund) PURPOSE The purpose of the Fund would be to aid in the creation of a collaborative resource environment devoted to research in new drug development.

August 29, 2002

Donations may be made through BRASddp.com Charitible Organization Number 88900 75797 RR0001 The Princess Margaret Cancer Foundation Special thanks to Cynthia Kinch, Editor and also Doug Bell and the team at Copyright Copy Centre in Etobicoke, who donate their services in the publication of our printed materials. Helping Hand 9th Edition Published and Edited by Maggie Bras. Layout and Design courtesy of Jane Brass.

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Helping Hand 2017  

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