Description:
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.
Title
- Brief Title: 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
- Official Title: 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
Clinical Trial IDs
- ORG STUDY ID:
GO42144
- SECONDARY ID:
2020-000084-22
- NCT ID:
NCT04449874
Conditions
- Non-Small Cell Lung Cancer
- Colorectal Cancer
- Advanced Solid Tumors
Interventions
| Drug | Synonyms | Arms |
|---|
| GDC-6036 | | Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II) |
| Atezolizumab | | Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) |
| Cetuximab | | Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) |
| Bevacizumab | | Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) |
| Erlotinib | | Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) |
| GDC-1971 | | Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) |
Purpose
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.
Trial Arms
| Name | Type | Description | Interventions |
|---|
| Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II) | Experimental | 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) | Experimental | Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab. | |
| Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) | Experimental | Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab. | |
| Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) | Experimental | Participants with solid tumors will receive GDC-6036 in combination with bevacizumab. | |
| Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) | Experimental | Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib. | |
| Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) | Experimental | 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. | |
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
contraception, 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.
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
Primary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0) |
Secondary Outcome Measures
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Concentrations of Atezolizumab |
| 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Concentrations of Bevacizumab |
| 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Serum Concentrations of Cetuximab |
| 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Duration of Response (DOR) 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. |
| Safety Issue: | |
| Description: | |
| Measure: | Progression-free survival (PFS) 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
| Measure: | 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. |
| Safety Issue: | |
| Description: | |
Details
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | Genentech, Inc. |
Trial Keywords
- KRAS G12C
- Non-Small Cell Lung Cancer
- Colorectal Cancer
- GDC-6036
- Metastatic Solid Tumor
- Atezolizumab
- Bevacizumab
- Cetuximab
- Erlotinib
- GDC-1971
- SHP2
Last Updated
August 6, 2021
