Study of GS-2121 Given Alone or in Combination in Adults With Advanced Solid Tumors

NCT06532565 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GS-US-579-67642024-511739-81
• Study Type: interventional
• Target: 154
• Locations: 2 countries
• Sites: 6

Brief Summary

The main goal of this first-in-human (FIH) study is to learn about the safety and dosing of GS-2121 when given alone or in combination with zimberelimab (ZIM) in participants with advanced solid tumors. The primary objectives of this study are:

• To assess the safety and tolerability of GS-2121 as monotherapy and GS-2121 in combination with zimberelimab 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-2121 as monotherapy and in combination with zimberelimab in participants with advanced solid tumors.

Conditions

Advanced Solid Tumors

Outcome Measures

Primary Outcomes (6)

• Parts A and B: Percentage of Participants with Adverse Events and Serious Adverse Events

  First dose up to 90 days post last dose (up to approximately 118 weeks)

• Parts A and B: Percentage of Participants with Laboratory Abnormalities

  First dose up to 90 days post last dose (up to approximately 118 weeks)

• Part A: Percentage of Participants with Dose-Limiting Toxicities (DLTs) During Dose Escalation

  DLTs are defined as any of the protocol-specified treatment-emergent adverse events (AEs) with onset within the DLT-evaluation period for the corresponding dose.

  Day 1 up to Day 21

• Parts C and D: Percentage of Participants with Adverse Events and Serious Adverse Events

  First dose up to 90 days post last dose (up to approximately 118 weeks)

• Parts C and D: Percentage of Participants with Laboratory Abnormalities

  First dose up to 90 days post last dose (up to approximately 118 weeks)

• Part C: Percentage of Participants with DLTs During Dose Escalation

  DLTs are defined as any of the protocol-specified treatment-emergent adverse events (AEs) with onset within the DLT-evaluation period for the corresponding dose.

  Day 1 up to Day 21

Secondary Outcomes (8)

• Parts A and B: Plasma Concentration of GS-2121 and Active Metabolite

  Predose and postdose up to end of treatment (up to 105 weeks)

• Parts A and B: PK Parameter: AUC0-24 of GS-2121

  Predose and postdose up to end of treatment (up to 105 weeks)

• Parts A and B: PK Parameter: Cmax of GS-2121

  Predose and postdose up to end of treatment (up to 105 weeks)

• Parts A and B: PK Parameter: Tmax of GS-2121

  Predose and postdose up to end of treatment (up to 105 weeks)

• Parts C and D: Plasma Concentration of GS-2121 and Active Metabolite

  Predose and postdose up to end of treatment (up to 105 weeks)

Study Arms (4)

Part A: GS-2121 Monotherapy Dose Escalation

EXPERIMENTAL

Participants will receive escalating doses of GS-2121 monotherapy until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.

Drug: GS-2121

Part B: GS-2121 Monotherapy Dose Expansion

EXPERIMENTAL

Participants with selected indications will receive GS-2121 monotherapy at the recommended dose for expansion.

Drug: GS-2121

Part C: Combination Dose Escalation of GS-2121 with Zimberelimab

EXPERIMENTAL

Participants will receive escalating doses of GS-2121 in combination with zimberelimab until disease progression, or until the participant meets other study drug discontinuation criteria as specified in protocol.

Drug: GS-2121; Drug: Zimberelimab

Part D: Combination Dose Expansion of GS-2121 with Zimberelimab

EXPERIMENTAL

Participants with selected indications will receive GS-2121 at the recommended dose for expansion in combination with zimberelimab.

Drug: GS-2121; Drug: Zimberelimab

Interventions

GS-2121 DRUG

Tablet administered orally

Part A: GS-2121 Monotherapy Dose Escalation; Part B: GS-2121 Monotherapy Dose Expansion; Part C: Combination Dose Escalation of GS-2121 with Zimberelimab; Part D: Combination Dose Expansion of GS-2121 with Zimberelimab

Zimberelimab DRUG

Administered intravenously

Also known as: GS-0122, AB122

Part C: Combination Dose Escalation of GS-2121 with Zimberelimab; Part D: Combination Dose Expansion of GS-2121 with Zimberelimab

Eligibility Criteria

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

You may qualify if:

• Participants diagnosed with histologically or cytologically confirmed advanced solid tumors who have progressed despite standard therapy, are intolerant to standard therapy, or are ineligible for standard therapy.
• Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 criteria.
• Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1.
• Tissue requirements:
• Parts A-D: Pre-treatment tumor tissue is required.
• Parts A and C backfill cohorts: Participants must agree to fresh pre- and on-treatment biopsies.
• Adequate organ function.

You may not qualify if:

• Positive serum pregnancy test or participant who is breastfeeding.
• Requirement for ongoing therapy with any prohibited medications.
• Any anti-cancer therapy, whether investigational or approved within protocol specified time prior to initiation of study including: major surgery (\<4 weeks), experimental therapy (\<21 days or \<5 half-lives whichever is shorter), approved immunotherapy or biologic therapy (\<28 days), approved chemotherapy (\<21 days or \<42 days for mitomycin or nitrosoureas), approved targeted small molecule therapy (\<14 days or \<5 half-lives whichever is longer), hormonal therapy or other adjunctive therapy for cancers other than cancer under evaluation in this study (\<14 days) or radiation therapy (\<21 days).
• Any prior allogeneic tissue/solid organ transplantation, including allogeneic stem cell transplantation.
• Have not recovered (ie, returned to Grade 1 or baseline) from AEs due to a previously administered agent.
• Have known active central nervous system (CNS) metastases and/or leptomeningeal disease (LMD).
• Diagnosis of immunodeficiency, either primary or acquired.
• History of autoimmune disease or active autoimmune disease that has required systemic treatment within 2 years prior to the start of study treatment.
• Have an active second malignancy.
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires systemic antibiotics, antifungals, or antivirals, respectively.
• History of pneumonitis requiring treatment with corticosteroids, interstitial lung disease, or severe radiation pneumonitis (excluding localized radiation pneumonitis).
• Ascites or pleural effusion that is symptomatic and/or requiring medical intervention.
• Have active hepatitis B virus (HBV) or hepatitis C virus (HCV), or HIV.
• Meet any of the following criteria for cardiac disease: Myocardial infarction or unstable angina pectoris within 6 months of enrollment. History of serious ventricular arrhythmia (ie, ventricular tachycardia or ventricular fibrillation), high-grade atrioventricular block, or other cardiac arrhythmias requiring antiarrhythmic medications (except for atrial fibrillation that is well controlled with antiarrhythmic medication). Mean QT interval corrected for heart rate using the Fridericia's formula (QTcF) ≥ 470 msec. New York Heart Association Class \> III congestive heart failure or known left ventricular ejection fraction \< 40%.
• Live vaccines within 28 days of initiation of study drug(s).

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (6)

Stanford Cancer Center

Palo Alto, California, 94305, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

NEXT Oncology

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

The Ottawa Hospital Cancer Centre

Ottawa, K1H 8L6, Canada

RECRUITING

Princess Margaret Cancer Centre

Toronto, M5G1Z5, Canada

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

zimberelimab

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

1-833-445-3230 (GILEAD-0); GileadClinicalTrials@gilead.com

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: July 29, 2024
• First Posted: August 1, 2024
• Study Start: July 26, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (4); CA (2)