Clinical Trial Brochures: GU/GI by alphabet-health

Clinical Trial Brochures

For more information on the studies in this booklet, please contact GileadClinicalTrials@gilead.com

Last updated 05/25

Clinical program in GU/GI cancers

GC/GEJC/EAC

1L/2L+

(multicohort)

1L/2L+

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

Unmet Needs in GU/GI Cancers

Bladder cancer is the sixth most common cancer in the US, with an estimated 84,870 new cases and 17,420 deaths in 2025.1 The 5-year relative survival rate for people diagnosed with bladder cancer is 79.0%, however for those diagnosed with cancer that has metastasized, this rate drops to as low as 9.1%.1 Almost all bladder cancers are urothelial cancers.2

GI cancer includes cancers of the stomach, esophagus, pancreas, and colorectum. In 2025, there were estimated to be 274,080 new cases of these GI cancers in the US. The 5-year relative survival rate for these GI cancers ranges from 13.3% to 65.4%, depending on the cancer type.1

1. NCI. SEER cancer stat facts. Accessed May 12, 2025. Available at: https://seer.cancer.gov/statfacts/html/. 2. NCI. What Is Bladder Cancer? Accessed May 12, 2025. Available at: https://www.cancer.gov/types/bladder

For more information on the studies in this booklet, please visit gileadclinicaltrials.com

GU/GI trials by line of therapy

population clinical trials

STAR-221a

TROPHY U-01 Cohorts 4, 6, 7

EDGE-Gastrica

Arms A1, A2, A3, A4

ARC-8a

2L+

ARC-8a

EDGE-Gastrica

Arms B1, B2, C1

ARC-9a

research area

GC/GEJC/EAC Ph 3

mUC Ph 2

GC/GEJC/EAC

GC/GEJC/EAC Ph 2

Ph 1/2

mCRC

aIn collaboration with Arcus Biosciences.

1L, first line; 2L, second line; A2AR/A2BR, adenosine 2A receptor/adenosine 2B receptor; CD73, cluster of differentiation 73; chemo, chemotherapy; CRC, colorectal cancer; EAC, esophageal adenocarcinoma; GC, gastric cancer; GEJC, gastroesophageal junction cancer; GI, gastrointestinal; GU, genitourinary; m, metastatic; PDAC, pancreatic ductal adenocarcinoma; PD-1, programmed cell death protein 1; Ph, phase; TIGIT, T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains; Trop-2, trophoblast cell-surface antigen 2; UC, urothelial cancer.

molecular combinations and scientific focus molecules

scientiﬁc

focus areas

Tumor-intrinsic cell death Immune-mediated tumor killing

zimberelimab (PD-1) domvanalimab (TIGIT) chemo

sacituzumab govitecan (Trop-2) zimberelimab (PD-1) domvanalimab (TIGIT) chemo

zimberelimab (PD-1) domvanalimab (TIGIT) chemo

zimberelimab (PD-1) quemliclustat (CD73) chemo

zimberelimab (PD-1) domvanalimab (TIGIT) quemliclustat (CD73)

zimberelimab (PD-1) etrumadenant (A2AR/A2BR) quemliclustat (CD73) chemo

Tumor-permissive microenvironment

Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

STAR-221: A Randomized, Open-Label, Multicenter Phase 3 Trial of Domvanalimab, Zimberelimab, and Chemotherapy Versus Nivolumab and Chemotherapy in Patients With Previously Untreated Locally Advanced Unresectable or Metastatic Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinomaa

Study Design1

Patients

Locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma

N=1040

Randomization

OS Endpoints

Primary Endpoint

Endpoints

Zimberelimab + +

Domvanalimab A FOLFOX/CAPOXb

B Nivolumab + FOLFOX/CAPOXb

Key Eligibility Criteria1

Key Inclusion Criteria

• ≥18 years of age

• Histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma

Key Exclusion Criteria

• Underlying medical or psychiatric conditions that, in the Investigator’s or Sponsor’s opinion, will make the administration of study-specified therapy hazardous, including but not limited to:

ILD, including history of ILD or non-infectious pneumonitis. Active viral, bacterial, or fungal infections requiring parenteral treatment within 14 days of randomization

Clinically significant cardiovascular disease, such as New York Heart Association Class II or greater cardiac disease or cerebrovascular accident within 3 months prior to randomization, unstable angina, or new onset angina within 3 months prior to randomization, myocardial infarction within 6 months prior to randomization, or unstable arrhythmia within 3 months prior to randomization

• ECOG PS of 0 or 1

• ≥1 measurable target lesion per RECIST v1.1

History of prior solid-organ transplantation, including allogenic bone marrow transplantation

Dementia, psychiatric, or substance abuse disorders that would interfere with satisfying the requirements of the trial

• Known HER2+ tumor

• Known untreated, symptomatic, or actively progressing CNS (brain) metastases. Patients with leptomeningeal metastases are excluded from enrollment

• Received prior systemic treatment for locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma

• Disease progression within 6 months of completion of neoadjuvant or adjuvant therapy

CAPOX, combination regimen of capecitabine plus oxaliplatin; CNS, central nervous system; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FACT-Ga, Functional Assessment of Cancer Therapy-Gastric; FOLFOX, combination regimen of oxaliplatin, leucovorin, fluorouracil; GEJ, gastroesophageal junction; HER2, human epidermal growth factor receptor 2; ILD, interstitial lung disease; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; v, version.

References

1. Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT05568095

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

TROPHY U-01: A Phase 2 Open-Label Study of Sacituzumab Govitecan in Patients with Unresectable

Locally Advanced/Metastatic Urothelial Cancer

Study Design1,2

Cohort 1: 2L+

Cohort 2: 2L+

• Patients with locally advanced or metastatic UC

• Progressed after prior platinum-based and/or CPI-based therapies

Primary readout completed

• Patients with locally advanced or metastatic UC ineligible for platinum-based therapy

• Progressed after prior CPI-based therapies

Primary readout completed

• Patients with locally advanced or metastatic UC who are CPI-naive

Cohort 3: 1L

Cohort 4:c 1L

• Progressed after prior platinum-based therapies

Primary readout completed

• Patients with metastatic or unresectable locally advanced UC

• Cisplatin-eligible and treatment naive

Cohort 6:c

• Patients with metastatic or unresectable locally advanced UC

• Cisplatin-ineligible and treatment naive

• Patients with no prior systemic therapy for metastatic or unresectable locally advanced UC

+ Pembro 200 mg

Cohorts 1-4, 6, 7: Continue treatment until clinical progression, disease progression, or toxicity

Key Eligibility Criteria1

Key Inclusion Criteria

• ECOG PS of 0 or 1

• Adequate renal and hepatic function

• Adequate hematologic parameters without transfusional support

Endpoints1,2

Primary Endpoint

• Cohorts 1-4, 6, 7: ORRf

• Cohort 7: Safety and tolerability

Key Exclusion Criteria

• Active second malignancy

• Active CNS metastases and/or carcinomatous meningitis

• Active Hepatitis B or C

Key Secondary Endpoints

Cohorts 1-4, 6, 7:

• CBRf,g

• DORf,g

• PFSf,g

• OS

Cohorts 1-4, 6:

• Safety and tolerability

Cohorts 3, 4, 6, 7:

• ORRf,g

aCohort 5 has been canceled, effective December 2023. bSG 10 mg/kg intravenously on Days 1 and 8 of a 21-day cycle. cEnrollment complete. dSG and EV doses determined in Phase 1b. eArm 3 is optional dose optimization arm to evaluate SG at 1 dose level below the RP2D that may be enrolled based on the RP2D and the totality of emerging data from Cohort 7. fPer RECIST v1.1. gCohorts 3, 4, 6 & 7 will be evaluated by iRECIST v1.1. 1L, first line; 2L, second line; Ave, avelumab; Carbo, carboplatin; CBR, clinical benefit rate; Cis, cisplatin; CNS, central nervous system; CPI, checkpoint inhibitor; Dom, domvanalimab; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; EV, enfortumab vedotin; Gem, gemcitabine; iRECIST, Modified RECIST v1.1 for Immune-Based Therapeutics; ORR, objective response rate; OS, overall survival; Pembro, pembrolizumab; PFS, progression-free survival; RECIST, Response Evaluation Criteria in Solid Tumors; RP2D, recommended phase 2 dose; SG, sacituzumab govitecan; UC, urothelial cancer; v, version; Zim, zimberelimab.

References

1. Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT03547973

2. Gilead Sciences Inc. Data on File. TROPHY U-01 protocol (Amendment 12). May 10, 2024.

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

EDGE-Gastric: A Phase 2 Trial to Evaluate the Safety and Efficacy of Combination Therapies in Patients With Advanced Upper Gastrointestinal Tract Malignanciesa

Study Design1,2

Patients

Locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma

aIn collaboration with Arcus Biosciences. bSafety run-in cohort: Domvanalimab and zimberelimab co-administered Q4W via IV infusion over 60 minutes in addition to FOLFOX chemotherapy via IV infusion Q2W. After safety evaluation of co-administered domvanalimab and zimberelimab, patients will be randomized 1:1 to A3 and A4. cZimberelimab ± Domvanalimab will be administered Q4W via IV infusion over 30 minutes, in addition to FOLFOX IV infusion Q2W.

Key Eligibility Criteria1

Key Inclusion Criteria

• ≥18 years of age

• Patients with histologically confirmed diagnosis of locally advanced unresectable or metastatic gastric, GEJ, or esophageal adenocarcinoma with life expectancy ≥3 months as assessed by the Investigator

• ECOG PS of 0 or 1

• ≥1 measurable target lesion per RECIST v1.1

• Adequate organ and marrow function

• Able to provide an archival tumor sample that is representative of the cancer under investigation and suitable for central PD-L1 testing

Key Exclusion Criteria

• Patients with underlying medical conditions that, in the Investigator’s or Sponsor’s opinion, will make the administration of investigational products hazardous

• Only for Cohort A: Known HER2+ tumor

• Known untreated, symptomatic, or actively progressing central nervous system (brain) metastases. Patients with leptomeningeal metastases are excluded from enrollment

• Discontinued use of prior immune checkpoint therapy due to immune related adverse events; received prior treatment with an anti-TIGIT monoclonal antibody

• History of trauma or major surgery within 28 days prior to enrollment

Primary Endpoint

• ORRb

• Safety Endpoints1

bAs assessed by Investigator per RECIST v1.1.

Secondary Endpoints • ORR

PFSb

DCR

1L, first line; 2L, second line; ADA, anti-drug antibody; CPI, checkpoint inhibitor; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; FOLFOX, combination regimen of oxaliplatin, leucovorin, fluorouracil; GEJ, gastroesophageal junction; HER2, human epidermal growth factor receptor 2; ORR, objective response rate; OS, overall survival; PD-L1, programmed cell death ligand 1; PFS, progression-free survival; PK, pharmacokinetics; Q2W, every 2 weeks; Q4W, every 4 weeks; RECIST, Response Evaluation Criteria in Solid Tumors; TIGIT, T cell immunoreceptor with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibitory motif (ITIM) domains; v, version.

References

1. Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT05329766

2. Arcus Biosciences. Data on File. EDGE-Gastric Protocol (Version 4.0). January 25, 2024.

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

ARC-9: A Phase 1b/2, Open-Label, Randomized Platform Study Evaluating The Efficacy and Safety of Etrumadenant Based Treatment Combinations in Patients With Metastatic Colorectal Cancera

Endpoints1

Primary Endpoint

• Cohort A and B: PFSb

• Cohort C: ORRb

• All Cohorts: Safety

Secondary Endpoints

• Cohorts A and B: ORRb, OSb

• All Cohorts: PK, ADAs, DORb, DCRb

Key Eligibility Criteria1

Key Inclusion Criteria

• ≥18 years of age

• Histologically confirmed mCRC

• ≥1 measurable lesion per RECIST v1.1

• ECOG PS of 0 or 1

• Life expectancy ≥3 months

• Adequate hematologic and end-organ function

• Negative HIV, Hep B and Hep C antibody testing

Inclusion Criteria for Cohort A

• Disease progression following no more than one prior line of treatment for mCRC that consisted of oxaliplatin or irinotecan containing chemotherapy in combination with a biologic agent

Inclusion Criteria for Cohort B

• Disease progression during or following no more than two separate lines of treatment for mCRC that consisted of oxaliplatin, and irinotecan containing chemotherapy in combination with a biologic agent

Continued on next page

2L, second line; 3L third line; ADA, anti-drug antibody; Bev, bevacizumab; DCR, disease control rate; DOR, duration of response; ECOG PS, Eastern Cooperative Oncology Group performance status; Hep, hepatitis; HIV, human immunodeficiency virus; mCRC, metastatic colorectal cancer; mFOLFOX-6, modified FOLFOX-6 regimen (5-fluorouracil, leucovorin, and oxaliplatin); ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; Quemli, quemliclustat; RECIST, Response Evaluation Criteria in Solid Tumors; v, version; Zim, zimberelimab.

Reference

1. Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT04660812

2. Cecchini M, et al. Poster presentation at ASCO GI Virtual Congress 2021. Poster TPS150. January 15-17, 2021.

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

Continued from previous page

Key Eligibility Criteria (cont’d)1

Key Exclusion Criteria

• Previous anticancer treatment within 4 weeks prior to initiation of study treatment

• Prior allogeneic stem cell or solid organ transplant

• Treatment with systemic immunostimulatory agents within 4 weeks prior to initiation of study treatment

• Use of any live vaccines against infectious diseases within 28 days of first dose.

• Symptomatic, untreated, or actively progressing CNS metastases

• Current treatment with anti-viral therapy for HBV

• Structurally unstable bone lesions suggesting impending fracture

• History of leptomeningeal disease

• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan

• History of malignancy other than colorectal cancer within 2 years prior to screening, except for malignancies such as non-melanoma skin carcinoma or ductal carcinoma in situ

• Active tuberculosis

• Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiating study treatment

• Severe infection within 4 weeks (28 days) prior to initiation of study treatment

• Significant cardiovascular disease, unstable or new onset of angina within 3 months prior to initiation of treatment, or myocardial infarction within 6 months prior to study treatment or unstable arrhythmia

• Major surgical procedures, other than for diagnosis, within 4 weeks prior to initiation of study treatment, or anticipation of need for major surgical procedure during the study

Key Eligibility Criteria (cont’d)1

Key Exclusion Criteria (cont’d)

• Evidence of inherited bleeding diathesis or significant coagulopathy at risk of bleeding (i.e., in the absence of therapeutic anticoagulation)

• Prior treatment with an agent targeting the adenosine pathway

• Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain Barré syndrome, or multiple sclerosis

Exclusion Criteria for Cohorts A and B

• Prior treatment with immune checkpoint blockade therapies including anti-cytotoxic T lymphocyteassociated protein-4, and anti-PD-(L)1 therapeutic antibodies

• Mutation in the BRAF oncogene. Patients with unknown BRAF status will be required to undergo testing at a local laboratory and provide results at screening

CNS, central nervous system; CT, computed tomography; HBV, hepatitis B virus; IV, intravenous; PD-(L)1, programmed cell death (ligand) 1.

Reference

1. Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT04660812

2. Cecchini M, et al. Poster presentation at ASCO GI Virtual Congress 2021. Poster TPS150. January 15-17, 2021.

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

ARC-8:

A Phase 1 Study to Evaluate the Safety and Tolerability of Quemliclustat Combination Therapy in Patients With Gastrointestinal Malignanciesa

Study Design

Patients N~195

Cohort A

1L mPDAC

Dose escalation COMBINATION THERAPY

Quemliclustat

Gemcitabine/ nab-paclitaxel Zimberelimab

Cohort B

2L mPDAC

Cohort C

1L mPDAC

Dose expansion COMBINATION THERAPY

Quemliclustat + + Zimberelimab Gemcitabine/ nab-paclitaxel

Cohort D

1L mPDAC

aIn collaboration with Arcus Biosciences.

Quemliclustat + + Zimberelimab Gemcitabine/ nab-paclitaxel

Quemliclustat + + Zimberelimab Gemcitabine/ nab-paclitaxel + Quemliclustat Gemcitabine/nab-paclitaxel + Quemliclustat Gemcitabine/nab-paclitaxel

Endpoints

Primary Endpoint

• TEAEs

• DLTs

Secondary Endpoints

Key Eligibility Criteria

Key Inclusion Criteria

• Histologically or cytologically confirmed mPDAC

• Naïve to any prior treatment, including chemotherapy, biological therapy, or targeted therapy for metastatic disease

Prior adjuvant therapy (including chemotherapy and/ or radiotherapy) for PDAC is permitted if neoadjuvant or adjuvant therapy was completed ≥6 months prior to study enrollment. Prior adjuvant therapy may include nab-paclitaxel or gemcitabine

Patients initially diagnosed with locally advanced

bPer RECIST v1.1.

pancreatic cancer who have undergone chemotherapy then resection and had no evidence of disease are eligible if relapse of metastatic disease has occurred and if the last dose of chemotherapy was received >6 months before study entry

Continued on next page

1L, first line; 2L, second line; ADA, anti-drug antibody; DCR, disease control rate; DLT, dose limiting toxicity; DOR, duration of response; m, metastatic ORR, overall response rate; OS, overall survival; PDAC, pancreatic ductal adenocarcinoma; PFS, progression-free survival; PK, pharmacokinetics; RECIST, Response Evaluation Criteria in Solid Tumors; TEAE, treatment emergent adverse event; v, version.

Reference

Clinicaltrials.gov website. Accessed May 12, 2025. https://www.clinicaltrials.gov/study/NCT04104672

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.

Continued from previous page

Key Eligibility Criteria (cont’d)

Key Inclusion Criteria (cont’d)

• ≥1 measurable lesion per RECIST v1.1. The measurable lesion must be outside of a radiation field if the patient received prior radiation

• ECOG PS of 0 or 1

• Confirmation that an archival tissue sample is available; if not, a new biopsy of a tumor must be obtained

• Prior radiation therapy for metastatic disease must have been completed

• Immunosuppressive doses of systemic medications, such as corticosteroids or absorbed topical corticosteroids (doses >10 mg/day prednisone or equivalent) must be discontinued ≥2 weeks (14 days) before investigational product administration. Physiologic doses of corticosteroids (≤10 mg/day of prednisone or its equivalent) or short pulses of corticosteroids (≤3 days) may be permitted

• Prior surgery that required general anesthesia or other major surgery as defined by the Investigator must be completed ≥4 weeks before investigational product administration

• Negative tests for hepatitis B surface antigen, hepatitis C virus antibody (or hepatitis C qualitative RNA; qualitative), and HIV-1 and HIV-2 antibody at screening

• Adequate organ and marrow function

Key Eligibility Criteria (cont’d)

Key Exclusion Criteria

• Significant cardiovascular disease (NYHA Class III-IV), myocardial infarction or cerebrovascular accident within 12 months of the first dose of investigational agent or history of arterial thromboembolic event, uncontrolled hypertension, unstable arrhythmia, or unstable angina within 3 months or venous thromboses within 1 month of the first dose of investigational agent

• Any active autoimmune disease or a documented history of autoimmune disease or history of a syndrome that required systemic steroids or immunosuppressive medications, except for vitiligo or resolved childhood asthma/atopy. Patients with asthma who require intermittent use of bronchodilators (such as albuterol) will not be excluded from this study

• Prior malignancy active within the previous year except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix, breast, or prostate cancer

• Has not recovered (i.e., ≤Grade 1 or baseline) from a non-hematologic AE due to a previously administered agent, except ≤Grade 2 alopecia or ≤Grade 2 neuropathy

AE, adverse event; ECOG PS, Eastern Cooperative Oncology Group performance status; HIV, human immunodeficiency virus; NYHA, New York Heart Association; RECIST, Response Evaluation Criteria in Solid Tumors; RNA, ribonucleic acid; v, version.

Reference Clinicaltrials.gov website. Accessed April 10, 2025. https://www.clinicaltrials.gov/study/NCT04104672

The safety and efficacy of these investigational agents and/or uses have not been established. There is no guarantee that they will become commercially available.