Study of GS-4528 in Adults With Solid Tumors

Study Overview
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Brief Summary
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The goals of this clinical study are to identify if GS-4528 alone or in combination with anti-programmed cell death protein 1 (PD-1) (Anti-PD-1) Monoclonal Antibody is safe and tolerable in people with solid tumors and to identify the recommended dose of GS-4528 for further development that is safe to give to people alone or in combination with Anti-PD-1 Monoclonal Antibody. The primary objectives of this study are: To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors. To identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended Phase 2 dose (RP2D) of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody in participants with advanced solid tumors.

Official Title
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A Phase 1 Study to Evaluate the Safety and Tolerability of GS-4528 as Monotherapy and in Combination With an Anti-PD-1 Monoclonal Antibody in Adults With Advanced Solid Tumors

Conditions
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Solid Tumor

Intervention / Treatment
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* Biological: GS-4528
* Drug: Zimberelimab


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Documented disease: Phase 1a dose escalation and backfill cohorts; Phase 1b dose escalation: Individuals with histologically or cytologically confirmed advanced solid tumors who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy. Phase 1a dose expansion: Individuals with histologically or cytologically confirmed select indications who have received, been intolerant to, or been ineligible for all treatment known to confer clinical benefit or have a contraindication to receive the therapy. Eastern Cooperative Oncology Group performance status 0 or 1. Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria. Adequate organ function. Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception. Tissue requirements: Phase 1a dose escalation, Phase 1a dose expansion, and Phase 1b dose escalation: Must provide pre-treatment adequate tumor tissue sample prior to enrolment. Phase 1a backfill cohorts: Individuals must have fresh pre-treatment and on-treatment biopsy for biomarker analysis. Life expectancy ≥ 3 months. Key Exclusion Criteria: Positive serum pregnancy test or lactating female. Prohibited concurrent anticancer therapy listed in the protocol. Any anti-cancer therapy, whether investigational or approved, within protocol specified time prior to initiation of study including: major surgery (<28 days), immunotherapy or biologic therapy (< 28 days), chemotherapy (< 21 days), targeted small molecule therapy (< 14 days or < 5 half-lives whichever is shorter), hormonal therapy or other adjunctive therapy (< 14 days) or radiotherapy (< 21 days). Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation. Diagnosis of immunodeficiency, either primary or acquired, or systemic steroid requirement of > 10 mg of prednisone or equivalent. History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy. History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment. Concurrent active second malignancy. Note: Individuals with a history of malignancy that have been completely treated, with no evidence of active cancer for 2 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence are allowed to enroll. Have known active central nervous system (CNS) metastases and/ or carcinomatous meningitis. Significant cardiovascular disease. Have active serious infection requiring antibiotics. Have active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis). Symptomatic ascites or pleural effusion. Live vaccines within 28 days of initiation of investigational product(s). Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1a: GS-4528 Monotherapy Dose Escalation<br>Participants will receive escalating doses of GS-4528 monotherapy to determine the maximum tolerated dose. | Biological: GS-4528<br>* Administered intravenously<br>|
| Experimental: Phase 1a: GS-4528 Monotherapy Dose Expansion<br>Participants will receive GS-4528 monotherapy at the dose determined in the escalation phase. | Biological: GS-4528<br>* Administered intravenously<br>|
| Experimental: Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab)<br>Participants will receive escalating doses of GS-4528 in combination with anti-PD1 monoclonal antibody (zimberelimab) to determine the maximum tolerated dose of GS-4528 as a combination therapy. | Biological: GS-4528<br>* Administered intravenously<br>Drug: Zimberelimab<br>* Administered intravenously.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Experiencing Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) |  | First dose date up to 90 days post last dose (Up to 24 months) | 
| Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs) |  | Day 1 up to 4 weeks | 
| Maximum Tolerable Dose (MTD) of GS-4528 |  | Day 1 up to 4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) parameter: Cmax of GS-4528 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody | Cmax is defined as the maximum observed concentration of drug. | Predose on Day 1 and post dose up to end of treatment (EOT, Up to 24 months) | 
| PK parameter: Cmin of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody | Cmin is defined as the minimum observed concentration of drug. | Predose on Day 1 and post dose up to EOT (Up to 24 months) | 
| PK parameter: AUC of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody | AUC is defined as the area under the concentration versus time curve. | Predose on Day 1 and post dose up to EOT (Up to 24 months) | 
| Serum Concentrations of GS-4528 as Monotherapy and in Combination with Anti-PD-1 Monoclonal Antibody |  | Predose on Day 1 and post dose up to EOT (Up to 24 months) | 
| Percentage of Participants who Develop Antidrug Antibody (ADA) Against GS-4528 |  | Predose on Day 1 and post dose up to 60 day follow-up (Up to 24 months) |