Study to Assess the Effects of GS-3583 in Participants With Advanced Solid Tumors

Gilead Sciences

Status and phase: Terminated; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: Carboplatin; Drug: Zimberelimab; Drug: 5-Fluorouracil; Drug: Docetaxel; Drug: GS-3583; Drug: Cisplatin

Study type: Interventional

Funder types: Industry

Identifiers

NCT04747470

GS-US-496-5657

Details and patient eligibility

About

This study is planned to be conducted in 2 parts: Part 1: Dose Escalation and Part 2: Safety Run-In and Randomized Expansion.

The primary objectives of Part 1 are 1) To characterize the safety and tolerability of GS-3583 as monotherapy in participants with advanced solid tumors. 2) To determine the maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-3583 as monotherapy in participants with advanced solid tumors.

The primary objectives of Part 2 is to assess the safety and tolerability and to determine the RP2D of GS-3583 in combination with zimberelimab (ZIM) and platinum (cisplatin or carboplatin) + 5-fluorouracil (5-FU) chemotherapy in participants with head and neck squamous cell carcinoma (HNSCC) (Cohort A) or in combination with docetaxel in participants with non-small cell lung cancer (NSCLC) (Cohort B).

Enrollment: 13 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Key Inclusion Criteria:

• Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor that is refractory to or intolerant of standard therapy or for which no standard therapy is available
• Have measurable disease on imaging based on Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
• Eastern Cooperative oncology Group (ECOG) performance status of ≤ 2
• Life expectancy of ≥ 3 months, in the opinion of the investigator
• Adequate organ function as assessed by hematological, renal, and hepatic parameters, and no clinically significant coagulopathy

Key Exclusion Criteria:

• Received prior systemic cytotoxic chemotherapy, biological therapy, radiotherapy, or major surgery within 3 weeks of Cycle 1 Day 1; a 1-week washout is permitted for palliative radiation to non-central nervous system (CNS) disease with sponsor approval

• Known severe hypersensitivity reactions (NCI CTCAE Grade ≥ 3) to fully human monoclonal antibodies or fusion proteins, GS-3583 formulation excipients, or severe reaction to immuno-oncology agents, such as colitis or pneumonitis requiring treatment with corticosteroids, any history of anaphylaxis, or uncontrolled asthma

• Concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ of the cervix, or superficial bladder cancer who has undergone potentially curative therapy with no evidence of disease. Individuals with other previous malignancies are eligible if disease free for > 2 years.

• Previous history of hematological malignancy, monoclonal gammopathy of unknown significance (MGUS) or other preleukemic states (Presence of clonal hematopoiesis of indeterminate potential (CHIP)/age related clonal hematopoiesis (ARCH) is acceptable)

• Known CNS metastasis(es), unless metastases are treated and stable and the individual does not require systemic corticosteroids for management of CNS symptoms at least 1 week prior to study treatment. Individuals with history of carcinomatous meningitis are excluded regardless of clinical stability.

• Active or history of autoimmune disease that has required systemic treatment within 2 years of the start of study treatment (ie, with use of disease-modifying agents, corticosteroids, or immunosuppressive drugs)

  • Note: Individuals with diabetes type 1, vitiligo, psoriasis, hypothyroid disease, or hyperthyroid disease, not requiring immunosuppressive treatment are eligible.

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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13 participants in 11 patient groups

Part 1: Cohort 1: GS-3583 675 μg

Experimental group

Description:

Participants with advanced solid tumors will receive GS-3583 675 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria.

Treatment:

Drug: GS-3583

Part 1: Cohort 2: GS-3583 2000 μg

Experimental group

Description:

Participants with advanced solid tumors will receive GS-3583 2000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria.

Treatment:

Drug: GS-3583

Part 1: Cohort 3: GS-3583 6000 μg

Experimental group

Description:

Participants with advanced solid tumors will receive GS-3583 6000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria.

Treatment:

Drug: GS-3583

Part 1: Cohort 4: GS-3583 12000 μg

Experimental group

Description:

Participants with advanced solid tumors will receive GS-3583 12000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria.

Treatment:

Drug: GS-3583

Part 1: Cohort 5: GS-3583 20000 μg

Experimental group

Description:

Participants with advanced solid tumors will receive GS-3583 20000 μg on Days 1 and 15 of Cycle 1 and on Day 1 of each subsequent 28-day cycle for up to 13 cycles (up to 52 weeks) or until the participant met study treatment discontinuation criteria.

Treatment:

Drug: GS-3583

Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy

Experimental group

Description:

Participants with head and neck squamous cell carcinoma (HNSCC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m\^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 28- day cycle up to 6 cycles + 5-5-flourouracil (5-FU) 1000 mg/m\^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles.

Treatment:

Drug: Cisplatin

Drug: GS-3583

Drug: 5-Fluorouracil

Drug: Carboplatin

Drug: Zimberelimab

Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy

Experimental group

Description:

Participants with non-small cell lung cancer (NSCLC) will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m\^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met.

Treatment:

Drug: GS-3583

Drug: Docetaxel

Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy

Experimental group

Description:

Participants with HNSCC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m\^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under the curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m\^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles.

Treatment:

Drug: Cisplatin

Drug: GS-3583

Drug: 5-Fluorouracil

Drug: Carboplatin

Drug: Zimberelimab

Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy

Experimental group

Description:

Participants with HNSCC will receive ZIM 360 mg, on Day 1 of each 21-day cycle up to 105 weeks + cisplatin 100 mg/m\^2 of BSA on Day 1 of each 21-day cycle up to 6 cycles + carboplatin area under th e curve 5 mg/mL/min on Day 1 of each 21-day cycle up to 6 cycles + 5-FU 1000 mg/m\^2 of BSA/day on Days 1 to 4 of 21-day cycle up to 6 cycles.

Treatment:

Drug: Cisplatin

Drug: 5-Fluorouracil

Drug: Carboplatin

Drug: Zimberelimab

Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy

Experimental group

Description:

Participants with NSCLC will receive GS-3583 at a dose determined in Part 1 on Day 1 of every 21-day cycles for up to 8 cycles + docetaxel 75 mg/m\^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met.

Treatment:

Drug: GS-3583

Drug: Docetaxel

Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy

Experimental group

Description:

Participants with NSCLC will receive docetaxel 75 mg/m\^2 on Day 1 of each 21-day cycle until 1 or more criteria for discontinuation are met.

Treatment:

Drug: Docetaxel