Recruiting
Phase 1

GS-2121

Sponsor:

Gilead Sciences

Code:

NCT06532565

Conditions

Advanced Solid Tumors

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

GS-2121

Zimberelimab

Study Details

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

Study ID

NCT06532565

Start date

Jul 26, 2024

Status verified date

Apr, 2026

Completion date

Jun, 2028

Anticipated

Primary completion date

Jun, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Key Inclusion Criteria:

  • 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:

1. Parts A-D: Pre-treatment tumor tissue is required.
2. Parts A and C backfill cohorts: Participants must agree to fresh pre- and on-treatment biopsies.
  • Adequate organ function.

Key Exclusion Criteria:

  • 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).

Note: Other protocol defined Inclusion/Exclusion criteria may apply.

Study Design

Enrollment

154 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Part A: GS-2121 Monotherapy Dose Escalation

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.

experimental: Part B: GS-2121 Monotherapy Dose Expansion

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

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

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.

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

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

Interventions

GS-2121

Tablet administered orally

Zimberelimab

Administered intravenously

Primary outcome measure

  • Parts A and B: Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: First dose up to 90 days post last dose (up to approximately 118 weeks) ]
  • Parts A and B: Percentage of Participants with Laboratory Abnormalities [ Time Frame: 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 [ Time Frame: Day 1 up to Day 21 ]
  • Parts C and D: Percentage of Participants with Adverse Events and Serious Adverse Events [ Time Frame: First dose up to 90 days post last dose (up to approximately 118 weeks) ]
  • Parts C and D: Percentage of Participants with Laboratory Abnormalities [ Time Frame: First dose up to 90 days post last dose (up to approximately 118 weeks) ]
  • Part C: Percentage of Participants with DLTs During Dose Escalation [ Time Frame: Day 1 up to Day 21 ]

Central Contacts and Locations

Central contacts

Gilead Clinical Study Information Center

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

Locations

Stanford Cancer Center

Recruiting

Palo Alto, California, United States, 94305

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

NEXT Oncology

Recruiting

San Antonio, Texas, United States, 78229

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

The Ottawa Hospital Cancer Centre

Recruiting

Ottawa, Canada, K1H 8L6

Princess Margaret Cancer Centre

Recruiting

Toronto, Canada, M5G1Z5

More Information

Sponsor

Gilead Sciences

Last update posted

Apr 21, 2026

Last verified

Apr, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Gilead Sciences on 2026-04-21.