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

• ClinicalTrials.gov Identifier: NCT04449874
• Recruitment Status: Recruiting
• First Posted: June 29, 2020
• Last Update Posted: April 18, 2024
• Sponsor: Genentech, Inc.
• Information provided by (Responsible Party): Genentech, Inc.

Tracking Information

• First Submitted Date: June 24, 2020
• First Posted Date: June 29, 2020
• Last Update Posted Date: April 18, 2024
• Actual Study Start Date: July 29, 2020
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 21, 2021)

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

Original Primary Outcome Measures (submitted: June 24, 2020)

• Percentage of Participants With Adverse Events (AEs) [ Time Frame: From baseline up until 28 days after the final dose ]
• Percentage of Participants With Dose-Limiting Toxicities (DLTs) [ Time Frame: Days 1-21 of Cycle 1 (a cycle is 21 days) ]
• Percentage of Participants With Changes From Baseline in Targeted Vital Signs [ Time Frame: From baseline up until 28 days after the final dose ]
• Percentage of Participants With Changes From Baseline in Targeted Clinical Laboratory Test Results [ Time Frame: From baseline up until 28 days after the final dose ]
• Percentage of Participants With Changes From Baseline in Targeted ECG Parameters [ Time Frame: From baseline up until 28 days after the final dose ]

Current Secondary Outcome Measures (submitted: August 4, 2022)

• 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. ]
• 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. ]

Original Secondary Outcome Measures (submitted: June 24, 2020)

• Plasma Concentration of GDC-6036 [ Time Frame: From baseline up until 28 days after the final dose or at study treatment discontinuation visit ]
• 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: Up to 42 months ]
• 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: Up to 42 months ]
• 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: Up to 42 months ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• 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
• 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 Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Non-Small Cell Lung Cancer
• Colorectal Cancer
• Advanced Solid Tumors

Intervention

• Drug: GDC-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).
• Drug: Atezolizumab
  A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.
• 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.
• Drug: Bevacizumab
  A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.
• Drug: Erlotinib
  150 mg of erlotinib will be administered PO QD in 21 day cycles.
• Drug: GDC-1971
  The starting dose of GDC-1971 will be determined from its single-agent dose escalation.
• Drug: Inavolisib
  The starting dose of inavolisib will be determined from its single-agent dose escalation.

Study Arms

• 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.

  Intervention: Drug: GDC-6036
• 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.
  Interventions:

  • Drug: GDC-6036
  • Drug: Atezolizumab
• Experimental: Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)
  Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.
  Interventions:

  • Drug: GDC-6036
  • Drug: Cetuximab
• Experimental: Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)
  Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.
  Interventions:

  • Drug: GDC-6036
  • Drug: Bevacizumab
• 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.
  Interventions:

  • Drug: GDC-6036
  • Drug: Erlotinib
• Experimental: Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)

  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.

  Interventions:

  • Drug: GDC-6036
  • Drug: GDC-1971
• Experimental: Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)

  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.

  Interventions:

  • Drug: GDC-6036
  • Drug: Inavolisib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: August 4, 2022): 498
• Original Estimated Enrollment (submitted: June 24, 2020): 108
• Estimated Study Completion Date: November 30, 2024
• Estimated Primary Completion Date: November 30, 2024 (Final data collection date for primary outcome measure)

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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Reference Study ID Number: GO42144 whttps://forpatients.roche.com/; 888-662-6728 (U.S. and Canada); global-roche-genentech-trials@gene.com

• Listed Location Countries: Australia, Belgium, Brazil, Canada, Germany, Hungary, Israel, Italy, Kenya, Korea, Republic of, Netherlands, New Zealand, Norway, Poland, Russian Federation, Spain, Switzerland, United Kingdom, United States
• Removed Location Countries: France

Administrative Information

• NCT Number: NCT04449874
• Other Study ID Numbers: GO42144; 2020-000084-22 ( EudraCT Number ); 2023-506311-18-00 ( Other Identifier: EU CT Number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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).

• Current Responsible Party: Genentech, Inc.
• Original Responsible Party: Same as current
• Current Study Sponsor: Genentech, Inc.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Clinical Trials; Genentech, Inc.

• PRS Account: Genentech, Inc.
• Verification Date: April 2024