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

NCT04747470 | Terminated Phase 1 Results FDA Drug

• 1 other identifier: GS-US-496-5657
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 4

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

Outcome Measures

Primary Outcomes (4)

• Parts 1 and 2: Percentage of Participants Experiencing Dose Limiting Toxicities (DLTs)

  DLT was defined as any toxicity (hematologic, non-hematologic, dosing/procedures-related toxicities, or grade 5 event (ie death)) occurring with GS-3583 monotherapy during the DLT assessment period (from Day 1 up to Day 28) considered at least possibly related to GS-3583 monotherapy.

  Part 1: Day 1 through Day 28; Part 2: Day 1 through Day 21

• Parts 1 and 2: Percentage of Participants Experiencing Treatment-emergent Adverse Events (TEAEs) According to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0

  TEAEs were AEs with onset dates on or after the first dose and up to 90 days after the date of the last dose of study treatment or the day before initiation of subsequent therapy, whichever occurred first. TEAEs severity was graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.

  First dose date up to last dose date plus 90 days (Up to 4 months)

• Parts 1 and 2: Percentage of Participants With Laboratory Abnormalities According to the NCI CTCAE Version 5.0

  A treatment-emergent laboratory abnormality was defined as an increase of at least 1 toxicity grade from baseline at any time, up to 90 days after the last dose of study drug or the day before initiation of subsequent therapy, whichever occurred first. A treatment-emergent laboratory abnormality severity was graded according to the NCI CTCAE version 5.0. Grade 1: Mild; Grade 2: Moderate; Grade 3: Severe; Grade 4: Life-threatening; Grade 5: Fatal. Participants were counted at the highest AE grade experienced.

  First dose date up to last dose date plus 90 days (Up to 4 months)

• Parts 1 and 2: Percentage of Participants With GS-3583 Anti-drug Antibodies (ADAs) at Any Visit

  Participants were monitored for the development of ADAs throughout their treatment period with GS-3583 and at the end of study.

  Cycles 1and 3,pre-dose,End of Infusion (EOI);2,6 hours;Days 2,3,5,8,15 post Day 1EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI(Cycle length = 28 days in Part 1; 21 days for Part 2;infusion duration=60 minutes)

Secondary Outcomes (11)

• Part 1: Pharmacokinetic (PK) Parameter: AUCtau of GS-3583

  Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; Infusion duration=60 minutes)

• Part 1: PK Parameter: Cmax of GS-3583

  Cycles 1 and 3,pre-dose,EOI;2, 6 hours;Days 2, 3, 5, 8, 15 post Day 1 EOI;Day 15:Cycle 1:predose and EOI;2 hours post EOI;Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1;Infusion duration=60 minutes)

• Part 1: PK Parameter: Tmax of GS-3583

  Cycles 1 and 3, pre-dose, EOI; 2, 6 hours; Days 2, 3, 5, 8, 15 post Day 1 EOI; Day 15:Cycle 1:predose and EOI; 2 hours post EOI; Cycle 3:336 hours and Day 24 post EOI (Cycle length for all cycles=28 days in Part 1; infusion duration=60 minutes)

• Part 2: Confirmed Objective Response Rate (ORR)

  First dose date in Part 2 to End of Study (approximately 4.2 months)

• Part 2: Progression-free Survival (PFS)

  First dose date in Part 2 to End of Study (approximately 4.2 months)

Study Arms (11)

Part 1: Cohort 1: GS-3583 675 μg

EXPERIMENTAL

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.

Drug: GS-3583

Part 1: Cohort 2: GS-3583 2000 μg

EXPERIMENTAL

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.

Drug: GS-3583

Part 1: Cohort 3: GS-3583 6000 μg

EXPERIMENTAL

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.

Drug: GS-3583

Part 1: Cohort 4: GS-3583 12000 μg

EXPERIMENTAL

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.

Drug: GS-3583

Part 1: Cohort 5: GS-3583 20000 μg

EXPERIMENTAL

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.

Drug: GS-3583

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

EXPERIMENTAL

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.

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

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

EXPERIMENTAL

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.

Drug: GS-3583; Drug: Docetaxel

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

EXPERIMENTAL

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.

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

Part 2: Randomized Expansion Cohort A: Combination Anticancer Therapy

EXPERIMENTAL

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.

Drug: Zimberelimab; Drug: Cisplatin; Drug: Carboplatin; Drug: 5-Fluorouracil

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

EXPERIMENTAL

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.

Drug: GS-3583; Drug: Docetaxel

Part 2: Randomized Expansion Cohort B: Combination Anticancer Therapy

EXPERIMENTAL

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.

Drug: Docetaxel

Interventions

GS-3583 DRUG

Administered as an intravenous (IV) infusion

Part 1: Cohort 1: GS-3583 675 μg; Part 1: Cohort 2: GS-3583 2000 μg; Part 1: Cohort 3: GS-3583 6000 μg; Part 1: Cohort 4: GS-3583 12000 μg; Part 1: Cohort 5: GS-3583 20000 μg; Part 2: Randomized Expansion Cohort A: GS-3583 + Combination Anticancer Therapy; Part 2: Randomized Expansion Cohort B: GS-3583 + Combination Anticancer Therapy; Part 2: Safety Run-In Cohort A: GS-3583 + Combination Anticancer Therapy; Part 2: Safety Run-In Cohort B: GS-3583 + Combination Anticancer Therapy

Zimberelimab DRUG

Administered as an IV infusion

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

Cisplatin DRUG

Administered as an IV infusion

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

Carboplatin DRUG

Administered as an IV infusion

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

5-Fluorouracil DRUG

Administered as an IV infusion

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

Docetaxel DRUG

Administered as an IV infusion

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (4)

START Midwest

Grand Rapids, Michigan, 49546, United States

Location

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

Location

Oregon Health & Science University

Portland, Oregon, 97239, United States

Location

NEXT oncology

San Antonio, Texas, 78229, United States

Location

Related Publications (3)

• 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).

  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).

  RESULT

• 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).

  RESULT

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

zimberelimab; Cisplatin; Carboplatin; Fluorouracil; Docetaxel

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Gilead Clinical Study Information Center
• Organization: Gilead Sciences

GileadClinicalTrials@gilead.com

1-833-445-3230 (GILEAD-0)

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 5, 2021
• First Posted: February 10, 2021
• Study Start: March 25, 2021
• Primary Completion: November 7, 2022
• Study Completion: November 7, 2022
• Last Updated: September 3, 2024
• Results First Posted: September 3, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (4)