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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
498
The starting dose of GDC-6036 in the combination Arms B, C, D, E, F and G will be determined from Stage I Arm A (single-agent dose escalation).
A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.
Cetuximab will be administered at an initial dose of 400 milligram per square meter (mg/m\^2) IV infusion followed by 250 mg/m\^2 IV infusion weekly in 21 day cycles.
Percentage of Participants With Adverse Events (AEs)
Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
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.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)
Time frame: From Cycle 1 Day 1 through Day 21. A cycle is 21 days.
Plasma Concentrations of GDC-6036
Time frame: 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 Erlotinib
Time frame: 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
Time frame: 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 Inavolisib
Time frame: 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)
Time frame: 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.
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A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.
150 mg of erlotinib will be administered PO QD in 21 day cycles.
The starting dose of GDC-1971 will be determined from its single-agent dose escalation.
The starting dose of inavolisib will be determined from its single-agent dose escalation.
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
Yale Cancer Center
New Haven, Connecticut, United States
Dana Farber Cancer Institute
Boston, Massachusetts, United States
University of Oklahoma
Oklahoma City, Oklahoma, United States
Abramson Cancer Center
Philadelphia, Pennsylvania, United States
UPMC - Hillman Cancer Center
Pittsburgh, Pennsylvania, United States
St Vincent's Hospital Sydney
Darlinghurst, New South Wales, Australia
Slade Health Inward goods
Mount Kuring-Gai, New South Wales, Australia
...and 53 more locations
Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
Time frame: 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.
Progression-free survival (PFS) as determined by the investigator according to RECIST v1.1
Time frame: 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])
Time frame: 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])
Time frame: 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])
Time frame: 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 (Area Under the Curve [AUC])
Time frame: 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
Time frame: 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.