Clinical Trial Brochures: Cell Therapy by alphabet-health

Clinical Trial Brochures Cell Therapy

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

Last updated 04/25

Clinical program in Cell Therapy Contents

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. aIn collaboration with Arcellx, Inc

Cell therapy in hematology and oncology

Cell therapy is a unique therapeutic platform whereby a patient’s own cells are the starting point to create the treatment. Cell therapy modifies a patient’s own immune cells to target their cancer.1

Unlike most cancer treatments, CAR-T cell therapy is a onetime treatment, available through Authorized Treatment Centers (ATCs), including hospitals that have experience with CAR-T cell therapy. Kite therapies are available at over 500 ATCs globally, including more than 135 leading cancer hospitals in the United States.1,2

CAR, chimeric antigen receptor.

1. Gilead Q423 Resource Book (February 2024). Available at: https://s29.q4cdn.com/585078350/files/ doc_financials/2023/q4/GILD-Q423-Resource-Book-6-February-2024.pdf

2. Gilead Q324 Resource Book (November 2024). Available at: https://s29.q4cdn.com/585078350/files/ doc_financials/2024/q3/GILD-Q324-Resource-Book-6-November-2024.pdf

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

Cell Therapy trials by research area

Population Clinical trials

Research area

Hematological malignancies

Solid tumors

Autoimmune diseases

aManufacturing Innovation bIn collaboration with Arcellx, Inc cIn collaboration with the University of Pennsylvania dIn collaboration with Children’s Hospital of Philadelphia

1L, first line; 2L, second line; ALL, acute lymphoblastic leukemia; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CD19/20, cluster of differentiation 19/20; DLBCL, diffuse large B-cell lymphoma; EGFR, epidermal growth factor receptor; FL, follicular lymphoma; GBM, glioblastoma; GPC2, glypican 2; IL13Ra2, interleukin-13 receptor subunit alpha-2; LBCL, large B-cell lymphoma; MM, multiple myeloma; NHL, non-Hodgkin lymphoma; Ph, phase; R/R, relapsed/refractory

scientiﬁc focus areas

Tumor-intrinsic cell death

Molecules

Immune-mediated tumor/cell killing

axicabtagene ciloleucel

Tumor-permissive microenvironment

Target

CD19

Next-gen CD19 CAR-T KITE-197

CD19/20 bicistronic KITE-363

CD19/20 bicistronic KITE-753

axicabtagene ciloleucel

brexucabtagene autoleucel

anitocabtagene autoleucel

CD19

BCMA

EGFR IL13Ra2 CAR-T GPC2 CPC2 CAR-T

EGFR IL13Ra2

CD19/20 bicistronic KITE-363

References

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

2 Gilead Q424 Resource Book (February 2025) Available at: https://s29 q4cdn com/585078350/files/doc_financials/2024/q4/GILD-Q424-ResourceBook-11-February-2025 pdf

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.

ZUMA-22: A Phase 3, Randomized, Open-Label, Multicenter Study Evaluating the Efficacy of Axicabtagene Ciloleucel Versus Standard of Care Therapy in Patients With Relapsed/Refractory Follicular Lymphoma

Study Design1,2

Screening

Patients

2L+ R/R FL and high-risk FL

N~230

Enrollment/1:1 Randomization Rituximab + lenalidomide x 12 cycles 28-DAY CYCLE

Post-treatment assessment period and long-term follow-up

SOCTc Arm

x 6 cycles

CYCLE Rituximab + bendamustine x 6 cycles 28-DAY CYCLE

aFludarabine 30 mg/m2 IV & cyclophosphamide 500 mg/m2 IV on Days –5, –4, and –3

bSingle IV infusion of 2x106 CAR-T-cells/kg on Day 0�

cSOCT should start between 2 and 9 days after randomization

dThe CHOP regimen may include a prednisone-equivalent dose of any corticosteroid per institutional guidelines

Primary Endpoint

• PFSe Endpoints1

Secondary Endpoints

• CR ratee

• ORRe

• DORe

• Duration of CRe

• OS

• EFSe

eBlinded Central Assessment per Lugano Classification�

• TTNT

• Safety and tolerability

• PROs/QoL

Continued on next page

2L, second line; CAR, chimeric antigen receptor; CR, complete response; DOR, duration of response; EFS, event-free survival; FL, follicular lymphoma; IV, intravenous; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PRO, patient-reported outcome; QoL, quality of life; R/R, relapsed/refractory; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; SOCT, standard of care therapy; TTNT, time to next treatment

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.

Key Eligibility Criteria1-3

Key Inclusion Criteria

• ≥18 years of age

• Histologically-confirmed FL (Grade 1, 2, or 3a)

• R/R disease after first-line chemoimmunotherapy and high-risk disease with relapse or progression within 24 months of the initial course of chemoimmunotherapy (i.e., POD24), or R/R disease after ≥2 prior systemic lines of therapy

• ≥1 measurable lesion per the Lugano Classification

• Adequate renal, hepatic, pulmonary, and cardiac function

• ECOG PS of 0 or 1

Key Exclusion Criteria

• Presence of LBCL or transformed FL

• Small lymphocytic lymphoma

• Lymphoplasmacytic lymphoma

• Full-thickness involvement of the gastric wall by lymphoma

• FL Grade 3b

• Prior CD19-targeted therapy

• Prior CAR therapy or other genetically modified T-cell therapy

• Uncontrolled fungal, bacterial, viral, or other infection

• Active infection with HIV, HBV, or HCV

Note: Patients who are HIV-positive are eligible if taking appropriate anti-HIV medications, having an undetectable viral load by quantitative PCR, and a CD4 count >200 cells/μL

Note: Patients with a positive history of HBV or HCV are eligible to enroll with an undetectable viral load

If seropositive for HBV (hepatitis B surface antibody and/or hepatitis B core antibody positive), patients are eligible if HBsAg negative Continued from previous page

Key Eligibility Criteria (cont’d)1-3

Key Exclusion Criteria

(cont’d)

• History or presence of a CNS disorder

• Known history or CNS lymphoma involvement

• History of clinically significant cardiac disease within 6 months of randomization

• Neuropathy >Grade 2

• Females who are pregnant or breastfeeding

• Patients of both genders who are not willing to practice birth control

• History of autoimmune disease resulting in or requiring systemic immunosuppression and/or systemic diseasemodifying agents within the last 2 years

• Presence of any indwelling line or drain (e.g., percutaneous nephrostomy tube, indwelling Foley catheter, biliary drain, G/J-tube, pleural/peritoneal/ pericardial catheter, or Ommaya reservoirs). Dedicated central venous access catheters such as Port-a-Cath or Hickman catheter are permitted

CAR, chimeric antigen receptor; CD4/19, cluster of differentiation 4/19; CNS, central nervous system; ECOG PS, Eastern Cooperative Oncology Group performance status; FL, follicular lymphoma; G/J-tube, gastrostomy-jejunostomy tube; HBsAg, hepatitis B surface antigen; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; LBCL, large B-cell lymphoma; PCR, polymerase chain reaction; POD24, progression of disease within 24 months; R/R, relapsed/refractory�

References

1 Clinicaltrials gov Accessed May 12, 2025 https://www clinicaltrials gov/study/NCT05371093

2 Flinn IW, et al Poster presentation at ASCO 2023 Jun 2-6, 2023 Chicago, IL Poster TPS7579

3 Kite Pharma, Inc Data on File Zuma-22 Protocol (Amendment 2) August 11, 2022

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.

Study Design1-3

Patients R-chemotherapy (1 CYCLE) Screening

1L high-risk LBCL N~300

Enrollment/1:1 Randomization

CORTICOSTEROIDS (OPTIONAL)

Post-treatment assessment period and long-term follow-up

SOCT: Investigator’s choice of either R-CHOP or DA-EPOCH-R x 6 cycles 21-DAY CYCLE

aBridging therapy with R-CHOP or DA-EPOCH-R will be administered during the cell manufacturing period bFludarabine 30 mg/m2 IV & cyclophosphamide 500 mg/m2 IV on Days –5, –4, and –3

Endpoints

1,2

Primary Endpoint

• EFSc

Secondary Endpoints

• PFSc

• OS

• CR ratec

• Safety and tolerability

• PROs/QoL

Continued on next page

cBy Blinded Central Assessment�

1L, first line; CR, complete response; DA-EPOCH-R, dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab; EFS, event-free survival; IV, intravenous; LBCL, large B-cell lymphoma; OS, overall survival; PFS, progression-free survival; PO, by mouth; PRO, patientreported outcome; QoL, quality of life; R-chemotherapy, rituximab plus chemotherapy; R-CHOP, rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone; SOCT, standard of care therapy

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 Criteria1-3

Key Inclusion Criteria

• ≥18 years of age

• Histologically confirmed LBCL based on 2016 WHO classification by local pathology lab assessment, including the following:

DLBCL-NOS

HGBL (including HGBL with MYC and BCL2 and/ or BCL6 rearrangements (DHL/THL) based on FISH analysis, and HGBL-NOS

Note: Transformed DLBCL from follicular lymphoma or from marginal zone lymphoma is eligible if no prior treatment with anthracycline-containing regimen

• High-risk disease defined as an IPI score of 4 or 5 at initial diagnosis

• Ann Arbor Stage III or IV disease

• Have received only 1 cycle of R-chemotherapy

• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function

• Females of childbearing potential must have a negative serum or urine pregnancy test

Key Exclusion Criteria

• The following WHO 2016 subcategories by local assessment

T-cell/histiocyte-rich LBCL

Primary DLBCL of the CNS

Primary mediastinal (thymic) LBCL

B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma

Burkitt lymphoma

• Presence of detectable CSF malignant cells, brain metastases, or a history of CNS involvement of lymphoma

• Presence of cardiac lymphoma involvement

• Any prior treatment for LBCL other than the 1 cycle of R-chemotherapy

• Patients positive for HIV

Note: Patients positive for HIV and taking appropriate anti-HIV medications, with an undetectable viral load by PCR and a CD4 count >200 cells/μL are eligible to enroll

Key Eligibility Criteria

1-3 (cont’d)

Key Exclusion Criteria

(cont’d)

• Patients with a history of acute or chronic active hepatitis B or C infection

Note: Patients with a history of treated hepatitis B or C infection and undetectable viral load are eligible to enroll

• Medical conditions likely to interfere with assessment of safety or efficacy of study treatment. Please refer to protocol for further details

• History of clinically significant cardiac disease within 12 months before enrollment

• History of any medical condition requiring maintenance systemic immunosuppression/systemic disease modifying agents within the last 2 years

BCL2/6, B-cell lymphoma 2/6; CD4, cluster of differentiation 4; CNS, central nervous system; CSF, cerebrospinal fluid; DHL, double-hit lymphoma; DLBCL, diffuse large B-cell lymphoma; FISH, fluorescence in situ hybridization; HGBL, high-grade B-cell lymphoma; HIV, human immunodeficiency virus; IPI, International Prognostic Index; LBCL, large B-cell lymphoma; MYC, master regulator of cell cycle entry and proliferative metabolism; NOS, not otherwise specified; PCR, polymerase chain reaction; R-chemotherapy, rituximab plus chemotherapy; THL, triple-hit lymphoma; WHO, World Health Organization�

References

1 Clinicaltrials gov website Accessed April 10, 2025 https://www clinicaltrials gov/study/NCT05605899

2 Westin JR, et al Poster presentation at ASCO 2023 Jun 2-6, 2023 Chicago, IL Poster TPS7578

3 Kite Pharma, Inc Data on File Zuma-23 Protocol May 02, 2022

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.

iMMagine-1: A Phase 2, Multicenter Study

Evaluating the Safety and Efficacy of Anitocabtagene Autoleucel in Patients With Relapsed or Refractory Multiple Myelomaa

Study Design1,2

Consent, screening, enrollment

Leukapheresis

Patients

4L+

R/R MM

N~110

Post-treatment assessment (up to 24 months)e and long-term follow-upf

aIn collaboration with Arcellx bIf necessary, bridging therapy is allowed to control growth of MM disease while anitocabtagene autoleucel is being manufactured cFludarabine 30 mg/m2 IV & cyclophosphamide 300 mg/m2 IV on Days –5, –4, and –3 dAnitocabtagene autoleucel consists of autologous T cells that have been genetically modified ex vivo to express a D-domain CAR, followed by a CD8 hinge and transmembrane region that is fused to the intracellular signaling domains for 4-1BB and CD3ξ, that specifically recognizes BCMA The active substance of anitocabtagene autoleucel is CAR+ CD3+ T cells that have undergone ex vivo T-cell activation, gene transfer by replication-deficient lentiviral vector, and expansion eFollowing a single infusion of anitocabtagene autoleucel, both safety and efficacy data will be assessed� Efficacy will be assessed monthly for the first 6 months, then quarterly up to 2 years, or upon patient relapse fLong-term safety data will be collected under a separate long-term follow-up study for up to 15 years per health authority guidelines

Endpoints1

Primary Endpoint

• ORRg

Secondary Endpoints

• sCR or CR rateg

• Safety

• ORR in patients limited to 3 prior LOTg

• DORg

• VGPR and PR rateg

• Time to initial response

• PFS

• OS

• PK

• HRQoL

• Anti-anitocabtagene-autoleucel antibodies

• MRD negativity

• Time to progression

Continued on next page

gPer IMWG criteria as assessed by IRC

4L, fourth line; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CD3/8, cluster of differentiation 3/8; CR, complete response; DOR, duration of response; HRQoL, health-related quality of life; IMWG, International Myeloma Working Group; IRC, independent review committee; IV, intravenous; LOT, line of therapy; MM, mulitple myeloma; MRD, minimal residual disease; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; PK, pharmacokinetics; PR, partial response; R/R, relapsed/refractory; sCR, stringent complete response; VGPR, very good partial response

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.

Key Eligibility Criteria1

Key Inclusion Criteria

• ≥18 years of age

• R/R MM with ≥3 prior regimens of systemic therapy including a PI, IMiD, and anti-CD38 antibody and are refractory to the last line of therapy. For each line, 2 consecutive cycles are required unless best response after 1 cycle was PD

Note: IMWG criteria define refractory disease as disease progression on or within 60 days of a therapy

Note: Induction treatment with or without hematopoietic stem cell transplant and with or without maintenance is considered a single regimen

• Documented measurable disease including ≥1 of the following criteria:

Serum M-protein ≥1 g/dL

Urine M-protein ≥200 mg/24 hours

Involved serum free light chain ≥10 mg/dL with abnormal ĸ/λ ratio (i.e., >4:1 or <1:2)

• ECOG PS of 0 or 1

• Adequate bone marrow, renal, hepatic, pulmonary, and cardiac function

• Resolution of AEs from any prior systemic anticancer therapy, radiotherapy, or surgery to Grade 1 or baseline (except Grade 2 alopecia and Grade 2 sensory neuropathy)

• Life expectancy >12 weeks

• Male and female patients of childbearing potential must agree to use highly effective methods of birth control through 12 months after the dose of study treatment

• Willing to comply with and able to tolerate study procedures, including consent to participate in separate long-term safety follow-up lasting up to 15 years per FDA guidance

• Patient’s leukapheresis product from non-mobilized cells is received and accepted for cell processing by manufacturing site

Note: Leukapheresis will be performed only after all other eligibility criteria are confirmed

Key Eligibility Criteria1 (cont’d)

Key Exclusion Criteria

• Plasma cell leukemia or history of plasma cell leukemia

• Any of the following prior therapies:

Systemic treatment for MM or high-dose systemic steroid therapy within the 14 days prior to leukapheresis

Gene therapy or gene-modified cellular immune therapy

BCMA-directed therapy

Auto-SCT within 3 months prior to leukapheresis

Allo-SCT

• Solitary plasmacytomas without evidence of other measurable disease

• Active CNS involvement by malignancy or any sign of active or prior CNS pathologya

• History of allergy or hypersensitivity to study drug components

• Contraindication to fludarabine or cyclophosphamide

• Active malignancy not related to myeloma that has required therapy in the last 3 years or is not in complete remissionb

• Active hepatitis B or C infection at the time of screening,c or HIV seropositive

• Severe or uncontrolled intercurrent illness or laboratory abnormalitiesd

• Any significant medical condition, laboratory abnormality, or psychiatric illness that would prevent the patient from participating in study (or full access to medical records) as written including follow-up, the interpretation of data, or place the patient at unacceptable risk

• Any vaccine ≤6 weeks before leukapheresis and/ or anticipation of the need for such a vaccine during patient’s participation in the study

aIncluding but not limited to history of epilepsy, seizure, paresis, aphasia, stroke, subarachnoid hemorrhage or CNS bleed, severe brain injury, dementia, cerebellar disease, Parkinson’s disease, organic brain syndrome or psychosis� bExceptions to this criterion include successfully treated nonmetastatic basal cell or squamous cell skin carcinoma, or prostate cancer that does not require therapy cPatients with history of treated hepatitis B or C and have nondetectable viral DNA are eligible dIncluding but not limited to active infection, symptomatic CHF, other cardiac disease (unstable angina, arrhythmia, or MI within 6 months prior to screening), significant pulmonary dysfunction, uncontrolled thromboembolic events or recent severe hemorrhage within 1 year, PE within 12 months or DVT within 3 months of enrollment, autoimmune disease requiring immunosuppressive therapy within the last 24 months AE, adverse event; Allo, allogeneic; Auto, autologous; BCMA, B-cell maturation antigen; CD38, cluster of differentiation 38; CHF, congestive heart failure; CNS, central nervous system; DNA, deoxyribonucleic acid; DVT, deep vein thrombosis; ECOG PS, Eastern Cooperative Oncology Group performance status; FDA, Food and Drug Administration; HIV, human immunodeficiency virus; IMiD, immunomodulatory drug; IMWG, International Myeloma Working Group; MI, myocardial infarction; MM, multiple myeloma; PD, progressive disease; PE, pulmonary embolism; PI, proteasome inhibitor; R/R, relapsed/ refractory; SCT, stem cell transplant

References

1 Clinicaltrials gov website Accessed April 10, 2025 https://www clinicaltrials gov/study/NCT05396885

2 Freeman CL, et al Oral presentation at ASH 2024 December 7-10, 2024 San Diego, CA Abstract 1031

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.

iMMagine-3:

A

Phase 3, Randomized, Open-Label Study to Compare the Efficacy and Safety of Anitocabtagene

Autoleucel Versus Standard of Care Therapy in Patients With Relapsed/Refractory Multiple Myelomaa

Study Design1,2

2-4L R/R MM

IMiD and anti-CD38 mAb exposed N~450 Patients

Lymphodepleting chemotherapyc Leukapheresis Bridging corticosteroid therapyb (optional)

Enrollment/ 1:1 Randomization

SOCT: TREATMENT OF INVESTIGATOR CHOICEd

Anitocabtagene autoleucel

Single IV dose of 115±10×106 CAR+ CART-ddBCMA cells on Day 1

CYCLE

pomalidomide, bortezomib, and dexamethasone

CYCLE

daratumumab, pomalidomide, and dexamethasone

CYCLE

carﬁlzomib, daratumumab, and dexamethasone

CYCLE

carﬁlzomib and dexamethasone

Post-treatment assessment period and long term follow-upe

aIn collaboration with Arcellx bBridging therapy, if used, will be with the selected standard-of-care regimen per Investigator discretion cFludarabine 30 mg/m2 IV & cyclophosphamide 300 mg/m2 IV on Days –5, –4, and –3� dCycles will continue until unacceptable toxicity, progression per IMWG criteria, or patient withdrawal of consent, whichever occurs first eAll patients who will receive anitocabtagene autoleucel will be followed in the post-treatment followup period and will transition to a separate long-term follow-up study

In collaboration with

Endpoints

Primary Endpoint

• PFSf

Secondary Endpoints

• CR ratef

• Overall MRD negativityf

• OS

• ORRf

• Time to next treatment

• Safety

• Levels of anti-anitocabtagene autoleucel CAR antibodies

• MRD-negative CR/sCR and MRD-negative VGPR+

• Sustained MRD negativity

• DORf

• Time to progressionf

• Presence of replication-competent lentivirus (anitocabtagene autoleucel arm)

• PROs/QoL

• HCRU

Continued on next page

fPer IMWG criteria

2L, second line; 4L, fourth line; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CD38, cluster of differentiation 38; CR, complete response; DOR, duration of response; HCRU, healthcare resource utilization; IMiD, immunomodulatory drug; IMWG, International Myeloma Working Group; IV, intravenous; mAb, monoclonal antibody; MM, multiple myeloma; MRD, measurable residual disease; ORR, overall response rate; OS, overall survival; PFS, progression-free survival; PRO, patient-reported outcome; QoL, quality of life; R/R relapsed or refractory; sCR, stringent complete response; SOCT, standard of care therapy; VGPR, very good partial response

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.

Key Eligibility Criteria1

Key Inclusion Criteria

• ≥18 years of age

• ECOG PS of 0 or 1

• Documented evidence of progressive disease per IMWG within 12 months of the last dose of the last regimen

• Measurable disease at screening per IMWG criteria

Serum M-protein of ≥0.5 g/dL or urine M-protein of ≥200 mg/24 hours; or Light chain MM without measurable disease in the serum or urine: serum free light chain of ≥10 mg/dL and abnormal serum free light chain ratio

• Received 1 to 3 prior lines of anti-myeloma therapy, including an IMiD and an anti-CD38 mAb

Minimum of 2 consecutive cycles required

IMiD and anti-CD38 mAb do not need to be from the same regimen

• Eligible to receive at least 1 of the 4 SOCT regimens (PVd, DPd, KDd, or Kd) as determined by the Investigator

Key Eligibility Criteria1 (cont’d)

Key Exclusion Criteria

• Any of the following prior therapies:

BCMA-directed therapy

T-cell engager therapy

CAR-T-cell therapy or other genetically modified T-cell therapy

Auto-SCT within 12 weeks before randomization

Allo-SCT

High-dose systemic steroid therapy, or other immunosuppressive therapy within 14 days of randomization

• Active or prior history of CNS or meningeal involvement of MM

• Cardiac atrial or ventricular MM involvement

• History of or active plasma cell leukemia, Waldenström macroglobulinemia, POEMS syndrome, or amyloidosis

• Active malignancy (other than MM) requiring ongoing treatment within the last 24 months

• Myelodysplastic syndrome (even without ongoing treatment) is not permitted

• Contraindication to fludarabine or cyclophosphamide

• History of severe hypersensitivity reaction to dimethyl sulfoxide

• Life expectancy <12 weeks

Allo, allogeneic; Auto, autologous; BCMA, B-cell maturation antigen; CAR, chimeric antigen receptor; CD38, cluster of differentation 38; CNS, central nervous system; DPd, daratumumab, pomalidomide, and dexamethasone; ECOG PS, Eastern Cooperative Oncology Group performance status; IMiD, immunomodulatory drug; IMWG, International Myeloma Working Group; Kd, carfilzomib and dexamethasone; KDd, carfilzomib, daratumumab, and dexamethasone; mAb, monoclonal antibody; MM, multiple myeloma; POEMS, polyneuropathy, organomegaly, endocrinopathy, monoclonal protein (M-protein), and skin changes; PVd, pomalidomide, bortezomib, and dexamethasone; SCT, stem cell transplant; SOCT, standard of care therapy

References

1 Clinicaltrials gov website Accessed April 10, 2025 https://www clinicaltrials gov/study/NCT06413498

2 Freeman CL, et al Oral presentation at ASH 2024 December 7-10, 2024 San Diego, CA Abstract 1031

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.

EGFR IL13Ra2 CAR-T: A Phase 1, Open-label Study

Evaluating the Safety and Feasibility of CAR-TEGFR-IL13Ra2 Cells in Patients With EGFR-Amplified Recurrent Glioblastomaa

Study Design

Patients

EGFR Ampliﬁed Recurrent GBM N~18

Screening/ Enrollment

Single ﬁxed dose via intrathecal administration on Day 0

DLT observation period: 28 days post-initial treatment with CAR-T EGFR-IL13Ra2 cells (Day 0)c

Primary Endpoints

• TRAEsd

• DLTs

• MTDe Endpoints

Secondary Endpoints

• Proportion of patients who enroll on this study who received study treatment

• Frequency of manufacturing failures

• PFSf

• ORRf

• DORf

• OS

Key Eligibility Criteria

Key Inclusion Criteria

• ≥18 years of age

• IDH-wildtype GBM (as defined by WHO 2021 Classification of CNS Tumors) that has recurred following prior radiotherapy. For patients with tumors harboring methylation of the MGMT promoter, ≥12 weeks must have elapsed since completion of first-line radiotherapy

• Tumor tissue positive for wild-type EGFR amplification by NeoGenomics Laboratories. Archival tumor from patient’s initial surgery at time of original diagnosis or recently collected tumor from time of recurrence are acceptable

• Surgical tumor resection for disease control/ management or tumor biopsy to confirm tumor recurrence is clinically indicated in the opinion of the physician-investigator

• Adequate organ function

• Karnofsky Performance Status ≥60%

• Patients of reproductive potential must agree to use acceptable birth control methods

Key Exclusion Criteria

• Active hepatitis B or hepatitis C infection or any other active, uncontrolled infection

• Class III/IV cardiovascular disability according to the NYHA Classification

• Tumors primarily localized to the brain stem or spinal cord

• Severe, active co-morbidity in the opinion of the physician-investigator that would preclude participation in this study

• Receipt of bevacizumab within 3 months prior to physician-investigator confirmation of eligibility

• Active autoimmune disease requiring systemic immunosuppressive treatment equivalent to ≥10 mg daily of prednisone. Patients with autoimmune neurological diseases (such as MS or Parkinson’s) will be excluded

aIn collaboration with the University of Pennsylvania bIn the event that 2 or more DLTs occur in Cohort 1, then enrollment into Cohort 1 will be stopped and the dose will be de-escalated to 5x106 CART-EGFR-IL13Ra2 cells This de-escalated cohort will be identified as Cohort -1 cPlease see ClinicalTrials gov for further details on dose level evaluation dUsing NCI CTCAE v5 0 eAssessed by collection of AEs as graded by CTCAE fPer modified RANO criteria

AE, adverse event; CAR, chimeric antigen receptor; CTCAE; Common Terminology Criteria for Adverse Events; DLT, dose limiting toxicity; DOR, duration of response; EGFR, epidermal growth factor receptor; GBM, glioblastoma; IDH, isocitrate dehydrogenase; IL13Ra2, interleukin-13 receptor subunit alpha-2; MS, multiple sclerosis; MTD, maximum tolerated dose; NCI, National Cancer Institute; NYHA, New York Heart Association; ORR, objective response rate; OS, overall survival; PFS, progression free survival; RANO, Response Assessment in Neuro-Oncology; TRAE, treatment related adverse events; v, version; WHO, World Health Organization

Reference

Clinicaltrials gov Accessed March 05, 2025 https://clinicaltrials gov/study/NCT05168423

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.

GPC2 CAR-T: A Phase 1 Trial of GPC2-Directed

Chimeric Antigen Receptor Autologous T Cells for Relapsed or Refractory Neuroblastomaa

Study Design

Patients

Screening/Enrollment GPC2 CAR-T cells GPC2 CAR-T cells

Standard 3+3 trial design

Preliminarily evaluate the rate of response to GPC2 CAR-T cells and further characterize the safety proﬁle of GPC2 CAR-T cells

Post-treatment assessment period and long term follow-up

Primary Endpoints

• MTD

• AEs Endpoints

Secondary Endpoints

• Manufacturing feasibility of GPC2 CAR-T cells

• Persistence of GPC2 CAR-T cellsb

• ORRc

• Severity of AEs

aIn collaboration with the Children’s Hospital of Philadelphia bAs measured by PCR (or flow cytometry) analysis of whole blood to detect and quantify survival of GPC2 CAR-T cells over time cDetermined based on international Neuroblastoma Response Criteria

Key Eligibility Criteria

Key Inclusion Criteria

• ≥1 year of age

• Adequate organ function

• Adequate performance status defined as Lanksy or Karnofsky performance score ≥60

• Disease status

Patients must have high-risk neuroblastoma according to Children’s Oncology Group risk classification at the time of study enrollment

Histologically confirmed diagnosis of neuroblastoma that is recurrent/relapsed/persistent according to International Neuroblastoma Response Criteria

Patients must have evaluable or measurable disease at enrollment

Key Exclusion Criteria

• Patients with active hepatitis B or active hepatitis C

• Patients with HIV infection

• Patients with uncontrolled active infection

• Patients with primary or acquired immunodeficiency disorder

• Concurrent use of systemic steroids or immunosuppression at the time of cell infusion or cell collection, or a condition, in the treating physician’s opinion, that is likely to require steroid therapy or immunosuppression during collection or after infusion. Steroids for disease treatment at times other than cell collection or at the time of infusion are permitted. Use of physiologic replacement hydrocortisone or inhaled steroids is permitted as well

• Patients with actively progressing CNS metastases, including parenchymal or leptomeningeal involvement

• Active medical disorder that, in the opinion of the investigator, would substantially increase the risk of uncontrollable CRS and/or neurotoxicity.

• Patients with congestive heart failure (as defined by NYHA Classification III or IV), unstable angina, serious uncontrolled cardiac arrhythmia, a myocardial infarction within 6 months prior to study entry or a history of myocarditis

• Patients who have received any live vaccines within 30 days prior to enrollment

AE, adverse event; CAR, chimeric antigen receptor; CNS, central nervous system; CRS, cytokine release syndrome; GPC2, glypican 2; HIV, human immunodeficiency virus; NYHA, New York Heart Association; PCR, polymerase chain reaction; R/R, relapsed/refractory

Reference

Clinicaltrials gov Accessed April 10, 2025 https://clinicaltrials gov/study/NCT05650749

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.