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.

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.