Clinical Trials /

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

NCT04449874

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.

Related Conditions:
  • Colorectal Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

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

DrugSynonymsArms
GDC-6036Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II)
AtezolizumabArm B: GDC-6036 + Atezolizumab (Stage I and Stage II)
CetuximabArm C: GDC-6036 + Cetuximab (Stage I and Stage II)
BevacizumabArm D: GDC-6036 + Bevacizumab (Stage I and Stage II)
ErlotinibArm E: GDC-6036 + Erlotinib (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

NameTypeDescriptionInterventions
Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II)ExperimentalParticipants 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.
  • GDC-6036
Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)ExperimentalParticipants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.
  • GDC-6036
  • Atezolizumab
Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)ExperimentalParticipants with colorectal cancer will receive GDC-6036 in combination with cetuximab.
  • GDC-6036
  • Cetuximab
Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)ExperimentalParticipants with solid tumors will receive GDC-6036 in combination with bevacizumab.
  • GDC-6036
  • Bevacizumab
Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)ExperimentalParticipants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.
  • GDC-6036
  • Erlotinib

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 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: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: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.
Safety Issue:
Description:
Measure: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.
Safety Issue:
Description:
Measure: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.
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

Last Updated

January 25, 2021