A study to assess the safety, pharmacokinetics, and efficacy of GDC-6036 as a monotherapy and in combination with other cancer therapies in patients with advanced or metastatic solid tumors with a KRAS G12C mutation
Résumé de l'étude
The purpose of this study is to test GDC-6036 to be taken orally at different doses to find out if it is safe and effective alone or in combination with other cancer medications, and to understand how your body processes the drug. GDC-6036 (the study drug) has been developed to block a specific mutation (referred to as G12C) in the KRAS gene, which can promote the growth of cancer cells. When mice with tumors with the KRAS G12C mutation received GDC-6036, it slowed or stopped the growth of the cancer cells. This will be the first time GDC-6036 is administered to humans. This means that the therapeutic efficacy has not yet been demonstrated. In this study, patients with non-small cell lung cancer (a type of lung cancer), colorectal cancer, or other types of cancer will receive GDC-6036. GDC-6036 will be given either alone or in combination with other cancer medications. All patients will undergo genetic testing before participating in the study to confirm that their cancer is positive for the KRAS G12C mutation.
(BASEC)
Intervention étudiée
This study consists of 7 treatment groups, referred to as "arms" (and with additional sub-arms), in which GDC-6036 is administered at different doses - either alone (Arm A) or in combination with other cancer treatments. In this study, the combination treatments are Atezolizumab (Arm B), Cetuximab (Arm C), Bevacizumab (Arm D), Erlotinib (Arm E), GDC-1971 (Arm F), and Inavolisib (Arm G).
Patients will be enrolled in two phases per arm (A-G):
1. Phase I: Dose escalation phase, in which patients receive increasing doses of GDC-6036 to determine the maximum treatment dose that is safe and tolerable. Additionally, there are "Backfill" treatment groups (so-called "cohorts"; with specific doses that were considered safe in the dose escalation cohorts). Approximately 168 patients will be included in the dose escalation phase of the study.
2. Phase II: Dose expansion phase to assess GDC-6036 at a dose that has been shown to be safe and tolerable in Phase I, to obtain additional data on safety, tolerability, and pharmacokinetics, as well as preliminary evidence of clinical activity. Approximately 270-330 patients will be included in the dose expansion phase.
Patients will be enrolled based on the type of their cancer into Arms A–G.
In Arm A, GDC-6036 will be tested as a monotherapy in patients with solid tumors, colorectal cancer (CRC), and non-small cell lung cancer (NSCLC).
In Arm B, GDC-6036 will be tested in combination with Atezolizumab in patients with NSCLC. Atezolizumab is approved by health authorities and represents the standard treatment for certain types of lung cancer.
In Arm C, GDC-6036 will be tested in combination with Cetuximab in patients with CRC. Cetuximab is approved by health authorities and represents the standard treatment for certain types of colorectal cancer.
In Arm D, GDC-6036 will be tested in combination with Bevacizumab in patients with solid tumors. Bevacizumab is approved by health authorities and represents the standard treatment for certain types of lung cancer, colorectal cancer, and other cancers.
In Arm E, GDC-6036 will be tested in combination with Erlotinib in patients with NSCLC. Erlotinib is approved by health authorities and represents the standard treatment for certain types of lung cancer.
In Arm F, GDC-6036 will be tested in combination with GDC-1971 in patients with solid tumors, NSCLC, or CRC. GDC-1971 is an experimental drug and has only been studied in a limited number of people. GDC-1971 is intended to inhibit cancer growth by binding to the SHP2 protein, which supports the proliferation of cancer cells.
In Arm G, GDC-6036 will be tested in combination with Inavolisib in patients with solid tumors and NSCLC. Inavolisib is an experimental drug and has only been tested in a limited number of people. Inavolisib is intended to block a specific mutation (change) (referred to as G12C) in the KRAS gene, which can promote the growth of cancer cells.
(BASEC)
Maladie en cours d'investigation
Solid tumors that have spread to other parts of the body (or that are locally advanced)
(BASEC)
To be included in the study, patients must meet some of the main inclusion criteria, including: • Signed patient information and consent form • Histologically documented locally advanced or metastatic solid tumor with KRAS G12C mutation • Age ≥ 18 years • Women of childbearing potential must agree to remain abstinent or use contraception and agree to refrain from egg donation during the treatment phase and after the last dose of the study medication, as specified in the protocol. • Men who are not surgically sterile must agree to remain abstinent or use contraception and agree to refrain from sperm donation during the treatment phase and after the last dose of the study medication, as specified in the protocol. (BASEC)
Critères d'exclusion
• Malabsorption syndrome or another health issue that affects enteral absorption (swallowing pills) • Active metastases in the central nervous system • Clinically significant cardiovascular dysfunction or liver disease (BASEC)
Lieu de l’étude
Bâle, Berne, Genève
(BASEC)
Sponsor
Sponsor: Genentech, Inc. Paul Ku 1 DNA Way 94080-4990 South San Francisco, CA Sponsor's representative in Switzerland: PPD Switzerland GmbH c/o Dufour Treuhand AG Tiergartenrain 3 4054 Basel
(BASEC)
Contact pour plus d'informations sur l'étude
Personne de contact en Suisse
Simon Häfliger, Dr. med. MD, PhD
+41 31 632 41 14
simon.haefliger@clutterinsel.chInselspital, Universitätsspital Bern Klinik und Poliklinik für Medizinische Onkologie 3010 Bern
(BASEC)
Informations générales
Genentech, Inc.,
888-662-6728 (U.S. and Canada)
simon.haefliger@clutterinsel.ch(ICTRP)
Informations générales
Genentech, Inc.
888-662-6728 (U.S. and Canada)
simon.haefliger@clutterinsel.ch(ICTRP)
Informations scientifiques
Genentech, Inc.,
888-662-6728 (U.S. and Canada)
simon.haefliger@clutterinsel.ch(ICTRP)
Nom du comité d'éthique approbateur (pour les études multicentriques, uniquement le comité principal)
Ethikkommission Nordwest- und Zentralschweiz EKNZ
(BASEC)
Date d'approbation du comité d'éthique
26.08.2021
(BASEC)
Identifiant de l'essai ICTRP
NCT04449874 (ICTRP)
Titre officiel (approuvé par le comité d'éthique)
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 (BASEC)
Titre académique
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 (ICTRP)
Titre public
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 (ICTRP)
Maladie en cours d'investigation
Non-Small Cell Lung CancerColorectal CancerAdvanced Solid Tumors (ICTRP)
Intervention étudiée
Drug: GDC-6036Drug: AtezolizumabDrug: CetuximabDrug: BevacizumabDrug: ErlotinibDrug: GDC-1971Drug: Inavolisib (ICTRP)
Type d'essai
Interventional (ICTRP)
Plan de l'étude
Allocation: Non-Randomized. Intervention model: Sequential Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)
Critères d'inclusion/exclusion
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. (ICTRP)
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Critères d'évaluation principaux et secondaires
Percentage of Participants With Adverse Events (AEs);Percentage of Participants With Dose-Limiting Toxicities (DLTs) (ICTRP)
Plasma Concentrations of GDC-6036;Plasma Concentrations of Erlotinib;Plasma Concentrations of GDC-1971;Plasma Concentrations of Inavolisib;Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1);Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1;Progression-free survival (PFS) as determined by the investigator according to RECIST v1.1;Relationship Between GDC-6036 Exposure (Maximum Plasma Concentration Observed [Cmax]);Relationship Between GDC-6036 Exposure (Time to Maximum Plasma Concentration [Tmax]);Relationship Between GDC-6036 Exposure (Half-life [t1/2]);Relationship Between GDC-6036 Exposure (Area Under the Curve [AUC]);Relationship Between Tumor Pharmacodynamic Effects of GDC-6036 (ICTRP)
Date d'enregistrement
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Inclusion du premier participant
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Sponsors secondaires
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Contacts supplémentaires
Clinical Trials;Reference Study ID Number: GO42144 whttps://forpatients.roche.com/, global-roche-genentech-trials@gene.com, 888-662-6728 (U.S. and Canada), Genentech, Inc., (ICTRP)
ID secondaires
2020-000084-22, 2023-506311-18-00, GO42144 (ICTRP)
Résultats-Données individuelles des participants
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Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04449874 (ICTRP)
Résultats de l'essai
Résumé des résultats
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Lien vers les résultats dans le registre primaire
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