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

Purpose

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).

Condition

  • Advanced Solid Tumor

Eligibility

Eligible Ages
Over 18 Years
Eligible Sex
All
Accepts Healthy Volunteers
No

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

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.

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Part A: GS-5319 Monotherapy Dose Escalation 		Participants will receive escalating doses of GS-5319 monotherapy, until disease progression, or until the participants meets other study drug discontinuation criteria as specified in protocol or up to 105 weeks, whichever occurs first to determine the recommended dose for dose expansion phase.
  • Drug: GS-5319
    Administered orally
Experimental
Part B: GS-5319 Monotherapy Dose Expansion 		Participants will be enrolled based on the selected indications to receive GS-5319 monotherapy at the recommended dose during the monotherapy dose expansion phase.
  • Drug: GS-5319
    Administered orally
Experimental
Part C: GS-5319 Monotherapy Dose Optimization 		Participants will be randomized based on the selected indications to receive GS-5319 monotherapy at one of the recommended doses during the monotherapy dose optimization phase.
  • Drug: GS-5319
    Administered orally
Experimental
Part D: GS-5319 Combination Therapy Dose Escalation 		Participants will receive escalating doses of GS-5319 as combination therapy with carboplatin, pemetrexed, pembrolizumab, until disease progression, or until the participants meets other study drug discontinuation criteria as specified in protocol or up to 105 weeks, whichever occurs first to determine the recommended dose for dose escalation phase.
  • Drug: GS-5319
    Administered orally
  • Drug: Carboplatin
    Administered intravenously
  • Drug: Pemetrexed
    Administered intravenously
  • Drug: Pembrolizumab
    Administered intravenously

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114

More Details

Status
Recruiting
Sponsor
Gilead Sciences

Study Contact

Gilead Clinical Study Information Center
1-833-445-3230 (GILEAD-0)
GileadClinicalTrials@gilead.com

Detailed Description

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.