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

NCT07128303 | Recruiting Phase 1 FDA Drug

• 2 other identifiers: GS-US-707-72972025-522397-36
• Study Type: interventional
• Target: 476
• Locations: 3 countries
• Sites: 11

Brief Summary

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).

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Percentage of Participants With Adverse Events (AEs) and Serous Adverse Events (SAEs)

  Up to 2 years

• Percentage of Participants Experiencing Laboratory Abnormalities

  Up to 2 years

• Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts

  Up to 21 days

Secondary Outcomes (6)

• Plasma Concentration of GS-5319

  Predose and postdose up to end of treatment (up to 2 years)

• Pharmacokinetic (PK) parameter: AUC0-last of GS-5319

  Predose and postdose up to end of treatment (up to 2 years)

• Pharmacokinetic (PK) parameter: AUC0-inf of GS-5319

  Predose and postdose up to end of treatment (up to 2 years)

• Pharmacokinetic (PK) parameter: AUCtau of GS-5319

  Predose and postdose up to end of treatment (up to 2 years)

• PK parameter: Cmax of GS-5319

  Predose and postdose up to end of treatment (up to 2 years)

Study Arms (4)

Part A: GS-5319 Monotherapy Dose Escalation

EXPERIMENTAL

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

Part B: GS-5319 Monotherapy Dose Expansion

EXPERIMENTAL

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

Part C: GS-5319 Monotherapy Dose Optimization

EXPERIMENTAL

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

Part D: GS-5319 Combination Therapy Dose Escalation

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Pemetrexed; Drug: Pembrolizumab

Interventions

GS-5319 DRUG

Administered orally

Part A: GS-5319 Monotherapy Dose Escalation; Part B: GS-5319 Monotherapy Dose Expansion; Part C: GS-5319 Monotherapy Dose Optimization; Part D: GS-5319 Combination Therapy Dose Escalation

Carboplatin DRUG

Administered intravenously

Part D: GS-5319 Combination Therapy Dose Escalation

Pemetrexed DRUG

Administered intravenously

Part D: GS-5319 Combination Therapy Dose Escalation

Pembrolizumab DRUG

Administered intravenously

Part D: GS-5319 Combination Therapy Dose Escalation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Gilead Sciences: lead

Study Sites (11)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

START San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Yonsei University Severance Hospital

Seoul, '06273, South Korea

RECRUITING

Seoul National University Hospital

Seoul, 03080, South Korea

RECRUITING

Asan Medical Center

Seoul, 05505, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Vall d'Hebron Institute of Oncology (VHIO)

Barcelona, 08035, Spain

RECRUITING

START Madrid - FJD - Hospital Fundación Jiménez Díaz - Phase I Clinical Trials Unit

Madrid, 28040, Spain

RECRUITING

START - Centro Oncológico Clara Campal

Madrid, 28050, Spain

RECRUITING

Related Links

• Gilead Clinical Trials Website

MeSH Terms

Interventions

Carboplatin; Pemetrexed; pembrolizumab

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Gilead Study Director

  Gilead Sciences

  STUDY DIRECTOR

Central Study Contacts

Gilead Clinical Study Information Center

CONTACT

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2025
• First Posted: August 17, 2025
• Study Start: August 28, 2025
• Primary Completion (Estimated): May 1, 2028
• Study Completion (Estimated): May 1, 2028
• Last Updated: August 19, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will not share

Locations

ES (3); KR (4); US (4)