Study of GS-4528 in Adults With Solid Tumors

Gilead Sciences

Status and phase: Active, not recruiting; Phase 1

Conditions: Solid Tumor

Treatments: Drug: Zimberelimab; Biological: GS-4528

Study type: Interventional

Funder types: Industry

Identifiers

NCT05840224

GS-US-616-6291

2022-502070-16 (Other Identifier)

Details and patient eligibility

About

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.

Enrollment: 182 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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182 participants in 3 patient groups

Phase 1a: GS-4528 Monotherapy Dose Escalation

Experimental group

Description:

Participants will receive escalating doses of GS-4528 monotherapy to determine the maximum tolerated dose.

Treatment:

Biological: GS-4528

Phase 1a: GS-4528 Monotherapy Dose Expansion

Experimental group

Description:

Participants will receive GS-4528 monotherapy at the dose determined in the escalation phase.

Treatment:

Biological: GS-4528

Phase 1b:Dose Escalation of GS-4528 in Combination With Anti-PD-1 Monoclonal Antibody (zimberelimab)

Experimental group

Description:

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.

Treatment:

Biological: GS-4528

Drug: Zimberelimab