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.
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
Interventions
Drug | Synonyms | Arms |
---|
GS-1423 | | Phase 1a, Part A - Dose Escalation |
mFOLFOX6 Regimen | | Phase 1b, Cohort 1 (Gastric Cancer) |
GS-1423 | | Phase 1a, Part B - Flat Dose Regimen |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Phase 1a, Part A - Dose Escalation | Experimental | Part 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 45 mg/kg on Day 1 of each 2-week cycle (Q2W) until the participants meets study treatment discontinuation criteria or for up to 1 year. | |
Phase 1a, Part B - Flat Dose Regimen | Experimental | Part B will consist of 3 adaptive cohorts. Based on PK, pharmacodynamics, and safety results from the Part A study, participants will be administered a flat dose of GS-1423 on Day 1 of each cycle QW, Q2W and/or every 3 weeks (Q3W) until the participant meets study treatment discontinuation criteria or for up to 1 year. | |
Phase 1b, Cohort 1 (Gastric Cancer) | Experimental | Safety 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. | |
Phase 1b, Cohort 2 (Paired Biopsy) | Experimental | Participants will receive GS-1423 at the dose level determined from Phase 1a Q2W until the participants meets study treatment discontinuation criteria or for up to 1 year. | |
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 (per local guidance) 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 anticancer 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 corticosteroids for management of
CNS symptoms at least 7 days prior to study treatment. Individuals with history of
carcinomatous meningitis are excluded regardless of clinical stability.
- 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 Part A, Phase 1b Cohort 1 Safety Run-in, 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 Part A and Phase 1a Part B, Pharmacokinetic (PK) Parameter: AUCtau of GS-1423 |
Time Frame: | Predose and 2, 6, 24, 48, 96, 168 hours postdose |
Safety Issue: | |
Description: | AUCtau is defined as concentration of drug over time (the area under the concentration verses time curve over the dosing interval). |
Measure: | For Phase 1a Part A and Phase 1a Part B, Percentage of Participants Experiencing Anti-Drug Antibody (ADA) Formation |
Time Frame: | Up to Posttreatment Month 3 |
Safety Issue: | |
Description: | |
Measure: | For Phase 1a Part A, Percentage of Participants Experiencing Treatment-Emergent Adverse Events |
Time Frame: | First dose date up to 1 year plus 30 days |
Safety Issue: | |
Description: | |
Measure: | For Phase 1b Cohort 1, Percentage of Participants Experiencing Treatment-Emergent Adverse Events |
Time Frame: | First dose date up to 2 years plus 30 days |
Safety Issue: | |
Description: | |
Measure: | For Phase 1a Part A, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities |
Time Frame: | First dose date up to 1 year plus 30 days |
Safety Issue: | |
Description: | |
Measure: | For Phase 1b Cohort 1, Percentage of Participants Experiencing Treatment-Emergent Grade 3 or 4 Laboratory Abnormalities |
Time Frame: | First dose date up to 2 years plus 30 days |
Safety Issue: | |
Description: | |
Measure: | For Phase 1a Part A, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) |
Time Frame: | First dose date up to 1 year plus 30 days |
Safety Issue: | |
Description: | |
Measure: | For Phase 1b Cohort 1, Percentage of Participants with Clinically Significant Abnormal 12-Lead Electrocardiogram (ECG) |
Time Frame: | First dose date up to 2 years plus 30 days |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 1 |
Primary Purpose: | Interventional |
Overall Status: | Terminated |
Lead Sponsor: | Gilead Sciences |
Last Updated
May 6, 2021