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

Study Identifier:
GO42144
CT.gov Identifier:
NCT04449874
EudraCT Identifier:
2020-000084-22
EU Trial (CTIS) Number:
2023-506311-18-00
Study Contact Information:
(210) 593-5651 or [email protected]
Recruitment Complete

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Study Summary

To evaluate the safety, pharmacokinetics (PK), and preliminary activity of GDC-6036 in patients with advanced or metastatic solid tumors with a KRAS G12C mutation.

To evaluates the safety, tolerability and pharmacokinetics of GDC-6036 and GDC-1971 alone, in combination, and in combination with other anticancer drugs in patients with advanced solid tumors

To evaluate safety, pharmacokinetics, antitumor activity, and biomarkers of response and resistance.

To assess divarasib monotherapy for patients with advanced or metastatic solid tumors that harbored KRAS G12C mutations.

we evaluated divarasib administered orally once daily (at doses ranging from 50 to 400 mg) in patients who had advanced or metastatic solid tumors that harbor a KRAS G12C mutation.

To report the long-term safety and clinical activity of single-agent divarasib in patients with advanced KRAS G12C-positive solid tumors.

Assessments included safety (NCI-CTCAE v5) and preliminary antitumor activity (RECIST v1.1).

Confirmed response was defined as complete or partial response on 2 consecutive tumor assessments at ≥4 weeks apart.

To study the safety and clinical activity of single-agent divarasib and in combination with the PD-L1 inhibitor atezolizumab in NSCLC patients.

Safety (NCI-CTCAE v5), pharmacokinetics, and preliminary antitumor activity (RECIST v1.1) were assessed.

To report clinical safety and activity of combination divarasib and migoprotafib (GDC-1971; SHP2 inhibitor) in patients with NSCLC. Safety (NCI-CTCAE v5), pharmacokinetics, and preliminary antitumor activity (RECIST v1.1) were assessed. Circulating tumor DNA (ctDNA) analyses were performed at Cycle 1 Day 1 and Cycle 3 Day 1.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Breast Cancers
  • Bowel (Colorectal)
  • Non-Small Cell Lung Cancer
  • Pancreas
  • Gastric
  • Solid Tumor
  • Endometrial
  • Esophageal
  • Neuroendocrine
  • Bile Duct
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: 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, E, F and G 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, 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. 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, E, F and G 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, E, F and G 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, E, F and G 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. 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. 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: GDC-1971 The starting dose of GDC-1971 will be determined from its single-agent dose escalation. 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. 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: Inavolisib The starting dose of inavolisib will be determined from its single-agent dose escalation. GDC-6036: GDC-6036 will be administered at specified dose, orally, once daily. GDC-1971: GDC-1971 will be administered at specified dose, orally, once daily.
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    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.
    • Histologically or cytologically documented solid tumor Advanced or recurrent for which standard therapy is ineffective or inappropriate, or for which no standard therapy exists ECOG PS of Grade 0 or 1 (GDC-6036 cohort and GDC-6036 + GDC-1971 cohort) KRAS G12C alteration has been identified
    Exclusion criteria
    • Active brain metastases.
    • Malabsorption or other condition that interferes with enteral absorption.
    • Clinically significant cardiovascular dysfunction or liver disease.
    • Patients who have difficultly taking oral medications Uncontrolled hypertension or hypercalcaemia (Cohort which GDC-6036 will be administered) Patients who have discontinued a prior KRAS G12C inhibitor because of toxicity assessed as related to the treatment (Cohorts which GDC-1971 will be administered) Patients who have discontinued a prior SHP2 inhibitor because of toxicity assessed as related to the treatment

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Victor Moreno Garcia
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Breast Cancers
    Bowel (Colorectal)
    Non-Small Cell Lung Cancer
    Pancreas
    Gastric
    Solid Tumor
    Endometrial
    Esophageal
    Neuroendocrine
    Bile Duct