A Study to Evaluate the Safety, Pharmacokinetics, and Activity of GDC-6036 Alone or in Combination in Participants With Advanced or Metastatic Solid Tumors With a KRAS G12C Mutation
Phase 1
Recruiting
- Conditions
- Non-Small Cell Lung CancerAdvanced Solid TumorsColorectal Cancer
- Interventions
- Registration Number
- NCT04449874
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 498
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) Erlotinib Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib. Arm G: GDC-6036 + Inavolisib (Stage I and Stage II) GDC-6036 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. Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) GDC-6036 Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab. Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II) GDC-6036 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. Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) GDC-6036 Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab. Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) GDC-6036 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. Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) GDC-6036 Participants with solid tumors will receive GDC-6036 in combination with bevacizumab. Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) GDC-6036 Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib. Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) Cetuximab Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab. Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) Atezolizumab Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab. Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) Bevacizumab Participants with solid tumors will receive GDC-6036 in combination with bevacizumab. Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) GDC-1971 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. Arm G: GDC-6036 + Inavolisib (Stage I and Stage II) Inavolisib 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Cycle 1 Day 1 through Day 21. A cycle is 21 days. Percentage of Participants With Adverse Events (AEs) 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 Outcome Measures
Name Time Method 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.
Trial Locations
- Locations (74)
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
Chao Family Comprehensive Cancer Center UCI
🇺🇸Orange, California, United States
Univ of Calif, San Francisco
🇺🇸San Francisco, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists - Sarasota
🇺🇸Sarasota, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
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