Study of GS-4528 in Adults With Solid Tumors
Study Details
Study Description
Brief Summary
The goals of this clinical study are to identify if GS-4528 alone or in combination with 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:
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To assess the safety and tolerability of GS-4528 as monotherapy and in combination with Anti-PD-1 Monoclonal Antibody (negative immunoregulatory human cell surface receptor programmed cell death 1) in participants with advanced solid tumors.
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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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 1a: GS-4528 Monotherapy Dose Escalation Participants will receive escalating doses of GS-4528 monotherapy to determine the maximum tolerated dose. |
Biological: GS-4528
Administered intravenously
|
| Experimental: Phase 1a: GS-4528 Monotherapy Dose Expansion Participants will receive GS-4528 monotherapy at the dose determined in the escalation phase. |
Biological: GS-4528
Administered intravenously
|
| Experimental: Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab) 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
Administered intravenously
Drug: Zimberelimab
Administered intravenously.
|
Outcome Measures
Primary Outcome Measures
- 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
- Pharmacokinetic (PK) parameter: Cmax of GS-4528 as Monotherapy and in Combination With Anti-PD-1 Monoclonal Antibody [Predose on Day 1 and post dose up to end of treatment (EOT, Up to 24 months)]
Cmax is defined as the maximum observed concentration of drug.
- PK parameter: Cmin 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)]
Cmin is defined as the minimum observed concentration of drug.
- PK parameter: AUC 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)]
AUC is defined as the area under the concentration versus time curve.
- 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)]
Eligibility Criteria
Criteria
Key Inclusion Criteria:
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Documented disease:
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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.
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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.
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Eastern Cooperative Oncology Group performance status 0 or 1.
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Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
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Adequate organ function.
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Individuals of childbearing potential who engage in heterosexual intercourse must agree to use method(s) of contraception.
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Tissue requirements:
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Phase 1a dose escalation, Phase 1a dose expansion, and Phase 1b dose escalation: Must provide pre-treatment adequate tumor tissue sample prior to enrolment.
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Phase 1a backfill cohorts: Individuals must have fresh pre-treatment and on-treatment biopsy for biomarker analysis.
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Life expectancy ≥ 3 months.
Key Exclusion Criteria:
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Positive serum pregnancy test or lactating female.
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Prohibited concurrent anticancer therapy listed in the protocol.
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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).
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Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
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Diagnosis of immunodeficiency, either primary or acquired, or systemic steroid requirement of > 10 mg of prednisone or equivalent.
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History of intolerance, hypersensitivity, or treatment discontinuation due to severe immune-related adverse events (irAEs) on prior immunotherapy.
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History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment.
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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.
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Have known active central nervous system (CNS) metastases and/ or carcinomatous meningitis.
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Significant cardiovascular disease.
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Have active serious infection requiring antibiotics.
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Have active hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
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History of pneumonitis, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
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Symptomatic ascites or pleural effusion.
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Live vaccines within 28 days of initiation of investigational product(s).
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Gilead Sciences
Investigators
- Study Director: Gilead Study Director, Gilead Sciences
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- GS-US-616-6291
- 2022-502070-16-00