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

NCT ID: NCT04747470

Last Updated: 2024-09-03

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1
• Total Enrollment: 13 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-03-25
• Study Completion Date: 2022-11-07

Brief Summary

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).

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1: Cohort 1: GS-3583 675 μg

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Part 1: Cohort 2: GS-3583 2000 μg

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Part 1: Cohort 3: GS-3583 6000 μg

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Part 1: Cohort 4: GS-3583 12000 μg

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Part 1: Cohort 5: GS-3583 20000 μg

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

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

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Zimberelimab

Intervention Type: DRUG

Administered as an IV infusion

Cisplatin

Intervention Type: DRUG

Administered as an IV infusion

Carboplatin

Intervention Type: DRUG

Administered as an IV infusion

5-Fluorouracil

Intervention Type: DRUG

Administered as an IV infusion

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

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Docetaxel

Intervention Type: DRUG

Administered as an IV infusion

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

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Zimberelimab

Intervention Type: DRUG

Administered as an IV infusion

Cisplatin

Intervention Type: DRUG

Administered as an IV infusion

Carboplatin

Intervention Type: DRUG

Administered as an IV infusion

5-Fluorouracil

Intervention Type: DRUG

Administered as an IV infusion

Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy

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.

Group Type: EXPERIMENTAL

Zimberelimab

Intervention Type: DRUG

Administered as an IV infusion

Cisplatin

Intervention Type: DRUG

Administered as an IV infusion

Carboplatin

Intervention Type: DRUG

Administered as an IV infusion

5-Fluorouracil

Intervention Type: DRUG

Administered as an IV infusion

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

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.

Group Type: EXPERIMENTAL

GS-3583

Intervention Type: DRUG

Administered as an intravenous (IV) infusion

Docetaxel

Intervention Type: DRUG

Administered as an IV infusion

Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy

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.

Group Type: EXPERIMENTAL

Docetaxel

Intervention Type: DRUG

Administered as an IV infusion

Interventions

GS-3583

Administered as an intravenous (IV) infusion

Intervention Type: DRUG

Zimberelimab

Administered as an IV infusion

Intervention Type: DRUG

Cisplatin

Administered as an IV infusion

Intervention Type: DRUG

Carboplatin

Administered as an IV infusion

Intervention Type: DRUG

5-Fluorouracil

Administered as an IV infusion

Intervention Type: DRUG

Docetaxel

Administered as an IV infusion

Intervention Type: DRUG

Eligibility Criteria

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

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gilead Sciences

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gilead Study Director

Role: STUDY_DIRECTOR

Gilead Sciences

Locations

START Midwest

Grand Rapids, Michigan, United States

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Oregon Health & Science University

Portland, Oregon, United States

NEXT oncology

San Antonio, Texas, United States

Countries

United States

References

Dauki AM, Jones A, Singh I, Rajakumaraswamy N, Qin A, et al. Population pharmacokinetics of GS-3583 in healthy volunteers and patients with advanced solid tumors [Poster II-083]. Clin Pharmacol Ther 2023 March; 113 (S5-S100).

Reference Type: RESULT

Brody J, Thompson JA, Tolcher AW, Kuhne MR, Huang XR, et al. Phase 1b Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Efficacy of GS3583, a FLT3 Agonist Fc Fusion Protein, in Patients With Advanced Solid Tumors [Poster TPS3147]. J Clin oncol 2021 June; 39 (15_suppl).

Reference Type: RESULT

Tolcher AW, Brody J, Rajakumaraswamy N, Lakhani NJ, Kuhne MR, Trowe T, et al. Phase 1b study of GS-3583, a novel FLT3 agonist Fc fusion protein, in patients with advanced solid tumors. [Poster TPS2566]. J Clin oncol 2022 June; 40 (16_suppl).

Reference Type: RESULT

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://www.gileadclinicaltrials.com/study/?id=GS-US-496-5657

Gilead Clinical Trials Website

Other Identifiers

GS-US-496-5657

Identifier Type: -

Identifier Source: org_study_id