Advanced Solid Tumors, Colorectal Cancer, Non-Small Cell Lung Cancer
Conditions
Keywords
KRAS G12C, Non-Small Cell Lung Cancer, Colorectal Cancer, GDC-6036, Metastatic Solid Tumor, Atezolizumab, Bevacizumab, Cetuximab, Erlotinib, Inavolisib, GDC-1971, SHP2
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.
Interventions
DRUGGDC-6036
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).
DRUGAtezolizumab
A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.
DRUGCetuximab
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.
DRUGBevacizumab
A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.
DRUGErlotinib
150 mg of erlotinib will be administered PO QD in 21 day cycles.
DRUGGDC-1971
The starting dose of GDC-1971 will be determined from its single-agent dose escalation.
DRUGInavolisib
The starting dose of inavolisib will be determined from its single-agent dose escalation.
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
| Percentage of Participants With Dose-Limiting Toxicities (DLTs) | From Cycle 1 Day 1 through Day 21. A cycle is 21 days. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Australia, Belgium, Brazil, Canada, Hungary, Israel, Italy, Kenya, Netherlands, New Zealand, Norway, Poland, South Korea, Spain, Switzerland, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Genentech, Inc.
Outcome results
None listed