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
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Gilead Sciences
- Enrollment
- 476
- Locations
- 14
- Primary Endpoint
- Percentage of Participants With Adverse Events (AEs) and Serous Adverse Events (SAEs)
Study Overview
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).
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.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- 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
- •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.
Arms & Interventions
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.
Intervention: GS-5319 (Drug)
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.
Intervention: GS-5319 (Drug)
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.
Intervention: Carboplatin (Drug)
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.
Intervention: Pemetrexed (Drug)
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.
Intervention: Pembrolizumab (Drug)
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.
Intervention: GS-5319 (Drug)
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.
Intervention: GS-5319 (Drug)
Outcomes
Primary Outcomes
Percentage of Participants With Adverse Events (AEs) and Serous Adverse Events (SAEs)
Time Frame: Up to 2 years
Percentage of Participants Experiencing Laboratory Abnormalities
Time Frame: Up to 2 years
Percentage of Participants Experiencing Laboratory Abnormalities
Time Frame: First Dose up to 30 days post last dose (Up to 105 weeks)
Percentage of Participants Experiencing any Dose-limiting Toxicities (DLTs) in Dose-escalation Cohorts
Time Frame: Up to 21 days
Percentage of Participants With Adverse Events (AEs) and Serous Adverse Events (SAEs)
Time Frame: First Dose up to 30 days post last dose (Up to 105 weeks)
Secondary Outcomes
- 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))
- PK parameter: Tmax of GS-5319(Predose and postdose up to end of treatment (up to 2 years))
- Plasma Concentration of GS-5319(Predose and postdose up to end of treatment (up to 105 weeks))
- PK parameter: Cmax of GS-5319(Predose and postdose up to end of treatment (up to 105 weeks))
- PK parameter: Tmax of GS-5319(Predose and postdose up to end of treatment (up to 105 weeks))
- Pharmacokinetic (PK) parameter: AUC0-24 of GS-5319(Predose and postdose up to end of treatment (up to 105 weeks))