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

Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorGilead Sciences

About this trial

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).

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Sequential

Treatments tested in this trial

  • GS-5319

    Drug

    Administered orally

  • Carboplatin

    Drug

    Administered intravenously

  • Pemetrexed

    Drug

    Administered intravenously

  • Pembrolizumab

    Drug

    Administered intravenously

Treatment groups

476 Participants
are divided into 4 treatment groups
Group A: Part A: GS-5319 Monotherapy Dose EscalationExperimental treatment 1 intervention
Group B: Part B: GS-5319 Monotherapy Dose ExpansionExperimental treatment 1 intervention
Group C: Part C: GS-5319 Monotherapy Dose OptimizationExperimental treatment 1 intervention
Group D: Part D: GS-5319 Combination Therapy Dose EscalationExperimental treatment 4 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
Up to 2 years
2

Percentage of Participants Experiencing Laboratory Abnormalities

Time frame
Up to 2 years
3

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

Time frame
Up to 21 days

Secondary outcomes

1

Plasma Concentration of GS-5319

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

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

AUC0-last is the area under the concentration-versus-time curve from time 0 to the time of the last measurable (quantifiable) drug concentration.

Time frame
Predose and postdose up to end of treatment (up to 2 years)
3

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

AUC0-inf is the area under the concentration-versus-time curve from time 0 extrapolated to infinite time, representing the total drug exposure after administration.

Time frame
Predose and postdose up to end of treatment (up to 2 years)
4

Pharmacokinetic (PK) parameter: AUCtau of GS-5319

AUCtau is defined as the area under the concentration-versus-time curve over one dosing interval at steady state.

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

Other outcomes

Sponsors and contacts

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