Study of GS-5319 Given Alone or in Combination in Adults With Solid Tumors

A Phase 1 Study to Evaluate the Safety and Tolerability of GS-5319 Monotherapy and Combination Therapy in Adults With MTAP-deleted Advanced Solid Tumors

The goal of this clinical study is to learn more about the study drug, GS-5319, its dosing, safety and tolerability when given as a single medication and as a combined medication in adults with solid tumors, where the participants show a specific gene alteration in the tumor. The gene helps produce methylthioadenosine phosphorylase (MTAP) enzyme. MTAP enzyme helps in normal growth of cells.

The primary objectives of the study are to assess the safety and tolerability of GS-5319 as monotherapy and combination therapy in participants with MTAP-deleted advanced solid tumors and identify the maximum tolerated dose (MTD)/maximum administered dose (MAD) and/or the recommended dose(s) for expansion (RDE).

This study includes four arms, Parts A, B, C, and D. Participants in Parts A, B, and D are assigned non-randomized. Participants in Part C are assigned using a randomization procedure.

Key Inclusion Criteria:

• Participants diagnosed with histologically or cytologically confirmed solid tumor types who have progressed despite standard therapy, are intolerant to standard therapy, or are ineligible for standard therapy in the advanced setting (locally-advanced or metastatic).

• Participant tumors are methylthioadenosine phosphorylase (MTAP)-deficient. Deoxyribonucleic acid (DNA) sequencing may be assessed locally such as by local next-generation sequencing (NGS) or by central laboratory assay when available.

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0 to 1.

• Adequate organ function

• Age ≥ 18yrs old ( ≥ 19 years old for patients in South Korea)

• Participants must meet the following tissue requirements:

  • pretreatment tumor tissue is required

Key Exclusion Criteria:

• Active second malignancy. Participants with a history of malignancy who have been completely treated, with no evidence of active cancer for 3 years prior to enrollment, or participants with surgically cured tumors with low risk of recurrence may be enrolled.
• Positive serum pregnancy test or participant who is breastfeeding.
• Requirement for ongoing therapy with any prohibited medications.
• Have not recovered (ie, returned to Grade 1 or baseline) from adverse events (AEs) due to a previously administered agent.
• Active and clinically relevant bacterial, fungal, or viral infection that is not controlled or requires systemic antibiotics, antifungals, or antivirals, respectively.
• Ascites or pleural effusion that is symptomatic and/or requiring medical intervention.
• Active human immunodeficiency virus (HIV)/hepatitis B virus (HBV)/hepatitis C virus (HCV) infection

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