Clinical Trials /

Study of GS-1423 in Participants With Advanced Solid Tumors

NCT03954704

Description:

For Phase 1a Part A, the primary objectives are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-1423 monotherapy in participants with advanced solid tumors. For Phase 1a Part B, the primary objective is to assess safety and tolerability of GS-1423 monotherapy in participants with advanced solid tumors. For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of GS-1423 in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma. For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of GS-1423 in combination with a chemotherapy regimen in participants with advanced gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR). For Phase 1b Cohort 2, the primary objective is to assess safety and tolerability of GS-1423 monotherapy in participants with advanced solid tumors.

Related Conditions:
  • Adenocarcinoma of the Gastroesophageal Junction
  • Gastric Adenocarcinoma
  • Malignant Solid Tumor
Recruiting Status:

Active, not recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Study of GS-1423 in Participants With Advanced Solid Tumors
  • Official Title: A Phase 1a/1b Study of GS-1423, an Anti-CD73-TGFβ-Trap Bifunctional Antibody, as Monotherapy or in Combination With a Chemotherapy Regimen in Subjects With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: GS-US-505-5452
  • SECONDARY ID: 2019‐004938‐41
  • NCT ID: NCT03954704

Conditions

  • Advanced Solid Tumors

Interventions

DrugSynonymsArms
GS-1423Phase 1a, Part A - Dose Escalation
mFOLFOX6 RegimenPhase 1b, Cohort 1 (Gastric)

Purpose

For Phase 1a, the primary objectives of this study are to assess safety and tolerability and to define the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) or recommended Phase 2 dose (RP2D) of GS-1423 monotherapy in participants with advanced solid tumors. For Phase 1b Cohort 1 safety run-in, the primary objective is to assess safety and tolerability and to define the DLT and MTD or RP2D of GS-1423 in combination with a chemotherapy regimen in participants with unresectable, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma. For Phase 1b Cohort 1 post safety run-in, the primary objective is to assess the preliminary efficacy of GS-1423 in combination with a chemotherapy regimen in participants with unresectable, recurrent or metastatic gastric or gastroesophageal junction adenocarcinoma, as assessed by the confirmed objective response rate (ORR).

Trial Arms

NameTypeDescriptionInterventions
Phase 1a, Part A - Dose EscalationExperimentalPart A will consist of dose escalation by an accelerated dosing design and a 3+3 dose escalation scheme. Participants will receive escalating dose levels GS-1423 of up to 30 mg/kg on Day 1 of each 2-week cycle (Q2W) for up to 1 year or until any progressive disease (PD) or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study.
  • GS-1423
Phase 1a, Part B - Flat Dose RegimenExperimentalPart B will consist of 2 adaptive cohorts. Based on PK, pharmacodynamics, and safety results from the Part A study, participants will be administered a flat dose of GS-1423 Q2W and/or every 3 weeks (Q3W) for up to 1 year or until any progressive disease (PD) or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study.
  • GS-1423
Phase 1b, Cohort 1 (Gastric)ExperimentalSafety run-in: A standard 3+3 dose escalation design will be used to determine the DLT and MTD or RP2D of GS-1423 in combination with mFOLFOX6. The planned starting dose of GS-1423 will be targeted to achieve the exposure at -1 dose of RP2D monotherapy (Q2W) determined from Phase 1a. GS-1423 will be administered in combination with mFOLFOX6. Post safety run-in: Approximately 70 participants will be enrolled to receive GS-1423 at the dose level determined from the safety run-in period, in combination with mFOLFOX6 regimen. Participants will receive GS-1423 on Day 1 of each 14-day cycle up to 2 years until PD, or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study. Participants will also receive mFOLFOX6 regimen Q2W for up to 12 cycles.
  • GS-1423
  • mFOLFOX6 Regimen
Phase 1b, Cohort 2 (Paired Biopsy)ExperimentalParticipants will receive GS-1423 at the dose level determined from Phase 1a Q2W for up to 1 year or until any progressive disease (PD) or unacceptable toxicity, substantial noncompliance with study procedures or study drug, study discontinuation or withdrawal from study.
  • GS-1423

Eligibility Criteria

        Key Inclusion Criteria:

          -  Diagnosis:

               -  For Phase 1a and Phase 1b Cohort 2, have a histologically or cytologically
                  confirmed diagnosis of a locally advanced or metastatic solid tumor for which no
                  standard therapy is available or standard therapy has failed, or

               -  For Phase 1b Cohort 1, have histologically or cytologically confirmed
                  unresectable, recurrent or metastatic gastric or gastroesophageal junction
                  adenocarcinoma who have not previously received systemic therapy for advanced
                  disease

          -  Measurable disease: Have measurable disease on imaging based on Response Evaluation
             Criteria in Solid Tumors (RECIST) Version 1.1

          -  Have a life expectancy of at least 3 months and an Eastern Cooperative Oncology Group
             (ECOG) performance status of 0 or 1

        Key Exclusion Criteria:

          -  Is currently participating and receiving study therapy or has participated in a study
             of an investigational agent and received study therapy or used an investigation device
             within 3 weeks of the first dose of treatment

          -  Has persisting toxicity related to prior therapy of National Cancer Institute-Common
             Terminology Criteria for Adverse Events Version 5.0 (NCI-CTCAE) Grade >1 severity

          -  Is expected to require any other form of systemic or localized antineoplastic therapy
             while on trial (including maintenance therapy with another agent, radiation therapy,
             and/or surgical resection)

          -  Has concurrent active malignancy other than nonmelanoma skin cancer, carcinoma in situ
             of the cervix or superficial bladder cancer who has undergone potentially curative
             therapy with no evidence of disease. Individuals with other previous malignancies are
             eligible if disease-free for >2 years

          -  Has a known central nervous system metastasis(es), unless metastases are treated and
             stable and the individual does not require systemic steroids

          -  Has active or history of autoimmune disease that has required systemic treatment
             within 2 years of the start of trial treatment

        Note: Other protocol defined Inclusion/Exclusion criteria may apply.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:For Phase 1a and Phase 1b Cohort 1, Percentage of Participants who had Dose Limiting Toxicities (DLTs) in Dose Escalation During the First 28 Days of Treatment
Time Frame:Up to 28 days
Safety Issue:
Description:DLTs refer to toxicities experienced during the first 28 days of study treatment that have been judged to be clinically significant and related to study treatment.

Secondary Outcome Measures

Measure:For Phase 1a, Pharmacokinetic (PK) Parameter: AUC of GS-1423
Time Frame:Predose and 2, 6, 24, 48, 96, 168 hours postdose
Safety Issue:
Description:AUC is defined as the area under the concentration versus time curve.
Measure:For Phase 1a, PK Parameter: t1/2 of GS-1423
Time Frame:Predose and 2, 6, 24, 48, 96, 168 hours postdose
Safety Issue:
Description:t1/2 is defined as the estimate of the terminal elimination half-life of the drug.
Measure:For Phase 1a, Percentage of Participants Experiencing Anti-Drug Antibody (ADA) Formation
Time Frame:Up to Posttreatment Month 3
Safety Issue:
Description:
Measure:For Phase 1a and Phase 1b, Percentage of Participants Experiencing Treatment-Emergent Adverse Events
Time Frame:First dose date up to last dose date (maximum: 1 year) plus 30 days
Safety Issue:
Description:
Measure:For Phase 1a and Phase 1b, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities
Time Frame:First dose date to last dose date (up to maximum of 1 year) plus 30 days
Safety Issue:
Description:
Measure:For Phase 1a and Phase 1b, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG)
Time Frame:First dose date to last dose date (up to maximum of 1 year) plus 30 days
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Gilead Sciences

Last Updated

January 30, 2020