A Phase Ia/Ib Dose-Escalation and Dose-Expansion Study Evaluating the Safety, Pharmacokinetics, and Activity of GDC-6036 as a Single Agent and in Combination With Other Anti-cancer Therapies in Patients With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
Overview
- Phase
- Phase 1
- Intervention
- GDC-1971
- Conditions
- Non-Small Cell Lung Cancer
- Sponsor
- Genentech, Inc.
- Enrollment
- 498
- Locations
- 64
- Primary Endpoint
- Percentage of Participants With Dose-Limiting Toxicities (DLTs)
- Status
- Active, Not Recruiting
- Last Updated
- 2 months ago
Overview
Brief Summary
This is a Phase I dose-escalation and dose-expansion study that will evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically documented advanced or metastatic solid tumor with KRAS G12C mutation.
- •Women of childbearing potential must agree to remain abstinent or use contraception, and agree to refrain from donating eggs during the treatment period and after the final dose of study treatment as specified in the protocol.
- •Men who are not surgically sterile must agree to remain abstinent or use a condom, and agreement to refrain from donating sperm during the treatment period and after the final dose of study treatment as specified in the protocol.
Exclusion Criteria
- •Active brain metastases.
- •Malabsorption or other condition that interferes with enteral absorption.
- •Clinically significant cardiovascular dysfunction or liver disease.
Arms & Interventions
Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with GDC-1971 PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with GDC-1971 PO in Stage II.
Intervention: GDC-1971
Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II)
Participants in Stage I will receive GDC-6036 administered orally once daily (PO QD). The dose will be increased in successive cohorts until a study-specific threshold is reached. Participants with select solid tumors will be treated with GDC-6036 PO QD in Stage II.
Intervention: GDC-6036
Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)
Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.
Intervention: GDC-6036
Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)
Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.
Intervention: Atezolizumab
Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)
Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.
Intervention: GDC-6036
Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)
Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.
Intervention: Cetuximab
Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.
Intervention: GDC-6036
Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.
Intervention: Bevacizumab
Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)
Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.
Intervention: GDC-6036
Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)
Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.
Intervention: Erlotinib
Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with GDC-1971 PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with GDC-1971 PO in Stage II.
Intervention: GDC-6036
Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with inavolisib PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with inavolisib PO in Stage II.
Intervention: GDC-6036
Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with inavolisib PO in Stage I. Participants with select solid tumors will be treated with GDC-6036 in combination with inavolisib PO in Stage II.
Intervention: Inavolisib
Outcomes
Primary Outcomes
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame: From Cycle 1 Day 1 through Day 21. A cycle is 21 days.
Percentage of Participants With Adverse Events (AEs)
Time Frame: From Cycle 1 Day 1 until 28 days after the final dose (or as specified in the protocol). A cycle is 21 days.
Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
Secondary Outcomes
- Plasma Concentrations of Erlotinib(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Plasma Concentrations of GDC-1971(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Progression-free survival (PFS) as determined by the investigator according to RECIST v1.1(Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Plasma Concentrations of Inavolisib(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Plasma Concentrations of GDC-6036(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1(Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Relationship Between GDC-6036 Exposure (Area Under the Curve [AUC])(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Relationship Between Tumor Pharmacodynamic Effects of GDC-6036(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Relationship Between GDC-6036 Exposure (Half-life [t1/2])(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)(Every 6 weeks from Cycle 1 Day 1 until study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Relationship Between GDC-6036 Exposure (Maximum Plasma Concentration Observed [Cmax])(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)
- Relationship Between GDC-6036 Exposure (Time to Maximum Plasma Concentration [Tmax])(Various timepoints from Cycle 1 Day 1 through study treatment discontinuation (within 28 days after the final dose of study drug). A cycle is 21 days.)