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

A Phase 1 Study to Evaluate the Safety and Tolerability of GS-2121 as Monotherapy and in Combination in Adults With Advanced Solid Tumors

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors
• Intervention / Treatment: Drug: Zimberelimab; Drug: GS-2121

• Study Type: Interventional
• Enrollment (Estimated): 154
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Gilead Clinical Study Information Center; Phone Number: 1-833-445-3230 (GILEAD-0); Email: GileadClinicalTrials@gilead.com

Study Locations

• Canada
  • Ottawa, Canada, K1H 8L6
    • Recruiting
    • The Ottawa Hospital Cancer Centre
  • Toronto, Canada, M5G1Z5
    • Recruiting
    • Princess Margaret Cancer Centre
• United States
  • California
    • Palo Alto, California, United States, 94305
      • Recruiting
      • Stanford Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Beth Israel Deaconess Medical Center
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Next Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: GS-2121; Tablet administered orally
Experimental: Part B: GS-2121 Monotherapy Dose Expansion; Participants with selected indications will receive GS-2121 monotherapy at the recommended dose for expansion.	Drug: GS-2121; Tablet administered orally
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.	Drug: Zimberelimab; Administered intravenously; Other Names: AB122; GS-0122; Drug: GS-2121; Tablet administered orally
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.	Drug: Zimberelimab; Administered intravenously; Other Names: AB122; GS-0122; Drug: GS-2121; Tablet administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	AUC0-24 is defined as the partial area under the concentration of drug over time between time 0 and time 24 hours. PK parameters will be estimated as applicable, based on the availability of data.	Predose and postdose up to end of treatment (up to 105 weeks)
Parts A and B: PK Parameter: Cmax of GS-2121	Cmax is defined as the maximum observed drug concentration. PK parameters will be estimated as applicable, based on the availability of data.	Predose and postdose up to end of treatment (up to 105 weeks)
Parts A and B: PK Parameter: Tmax of GS-2121	Tmax is defined as the time to maximum observed drug concentration. PK parameters will be estimated as applicable, based on the availability of data.	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)
Parts C and D: PK Parameter: AUC0-24 of GS-2121	AUC0-24 is defined as the partial area under the concentration of drug over time between time 0 and time 24 hours. PK parameters will be estimated as applicable, based on the availability of data.	Predose and postdose up to end of treatment (up to 105 weeks)
Parts C and D: PK Parameter: Cmax of GS-2121	Cmax is defined as the maximum observed drug concentration. PK parameters will be estimated as applicable, based on the availability of data.	Predose and postdose up to end of treatment (up to 105 weeks)
Parts C and D: PK Parameter: Tmax of GS-2121	Tmax is defined as the time to maximum observed drug concentration. PK parameters will be estimated as applicable, based on the availability of data.	Predose and postdose up to end of treatment (up to 105 weeks)

Collaborators and Investigators

• Sponsor: Gilead Sciences
• Investigators: Study Director: Gilead Study Director, Gilead Sciences

Publications and helpful links

Helpful Links

• Gilead Clinical Trials Website

Study record dates

Study Major Dates

• Study Start (Actual): July 26, 2024
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2028

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 1, 2024

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 20, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; zimberelimab
• Other Study ID Numbers: GS-US-579-6764; 2024-511739-81 (Other Identifier: European Medicines Agency)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No