Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04449874
Recruitment Status : Recruiting
First Posted : June 29, 2020
Last Update Posted : January 25, 2021
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Colorectal Cancer Advanced Solid Tumors Drug: GDC-6036 Drug: Atezolizumab Drug: Cetuximab Drug: Bevacizumab Drug: Erlotinib Phase 1

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 236 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : July 29, 2020
Estimated Primary Completion Date : August 31, 2023
Estimated Study Completion Date : August 31, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: 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.

Drug: GDC-6036
The starting dose of GDC-6036 in the combination Arms B, C, D and E will be determined from Stage I Arm A (single-agent dose escalation).

Experimental: 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.
Drug: GDC-6036
The starting dose of GDC-6036 in the combination Arms B, C, D and E will be determined from Stage I Arm A (single-agent dose escalation).

Drug: Atezolizumab
A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.

Experimental: Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)
Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.
Drug: GDC-6036
The starting dose of GDC-6036 in the combination Arms B, C, D and E will be determined from Stage I Arm A (single-agent dose escalation).

Drug: Cetuximab
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.

Experimental: Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)
Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.
Drug: GDC-6036
The starting dose of GDC-6036 in the combination Arms B, C, D and E will be determined from Stage I Arm A (single-agent dose escalation).

Drug: Bevacizumab
A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.

Experimental: 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.
Drug: GDC-6036
The starting dose of GDC-6036 in the combination Arms B, C, D and E will be determined from Stage I Arm A (single-agent dose escalation).

Drug: Erlotinib
150 mg of erlotinib will be administered PO QD in 21 day cycles.




Primary Outcome Measures :
  1. 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)

  2. Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: From Cycle 1 Day 1 through Day 21. A cycle is 21 days. ]

Secondary Outcome Measures :
  1. 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. ]
  2. 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. ]
  3. 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. ]
  4. 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. ]
  5. 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. ]
  6. Incidence of Anti-drug Antibodies (ADAs) to Atezolizumab during the study [ 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. ]
  7. Incidence of ADAs to Bevacizumab during the study [ 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. ]
  8. Incidence of ADAs to Cetuximab during the study [ 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. ]
  9. 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. ]
  10. 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. ]
  11. 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. ]
  12. 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. ]
  13. 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. ]
  14. 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. ]
  15. 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. ]
  16. 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. ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04449874


Contacts
Layout table for location contacts
Contact: Reference Study ID Number: GO42144 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

Locations
Show Show 70 study locations
Sponsors and Collaborators
Genentech, Inc.
Investigators
Layout table for investigator information
Study Director: Clinical Trials Hoffmann-La Roche
Layout table for additonal information
Responsible Party: Genentech, Inc.
ClinicalTrials.gov Identifier: NCT04449874    
Other Study ID Numbers: GO42144
2020-000084-22 ( EudraCT Number )
First Posted: June 29, 2020    Key Record Dates
Last Update Posted: January 25, 2021
Last Verified: January 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Genentech, Inc.:
KRAS G12C
Non-Small Cell Lung Cancer
Colorectal Cancer
GDC-6036
Metastatic Solid Tumor
Atezolizumab
Bevacizumab
Cetuximab
Erlotinib
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Colorectal Neoplasms
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases
Rectal Diseases
Bevacizumab
Cetuximab
Erlotinib Hydrochloride
Atezolizumab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors