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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Colorectal Cancer; Non-Small Cell Lung Cancer; Advanced Solid Tumors
• Intervention / Treatment: Drug: GDC-6036; Drug: Atezolizumab; Drug: Cetuximab; Drug: Bevacizumab; Drug: Erlotinib; Drug: GDC-1971; Drug: Inavolisib

• Study Type: Interventional
• Enrollment (Estimated): 498
• Phase: Phase 1

Contacts and Locations

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

Study Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • Recruiting
      • St Vincent's Hospital Sydney
    • Mount Kuring-gai, New South Wales, Australia, 2080
      • Recruiting
      • Slade Health Inward goods
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Recruiting
      • Alfred Health
    • North Melbourne, Victoria, Australia, 3051
      • Recruiting
      • Peter MacCallum Cancer Center
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Recruiting
      • Linear Clinical Research Limited
• Belgium
  • Edegem, Belgium, 2650
    • Recruiting
    • UZ Antwerpen
  • Liège, Belgium, 4000
    • Recruiting
    • CHU de Liège
  • Mechelen, Belgium, 2800
    • Recruiting
    • AZ St Maarten Campus Leopoldstr
• Brazil
  • MG
    • Belo Horizonte, MG, Brazil, 30150-221
      • Recruiting
      • Santa Casa de Misericordia de Belo Horizonte - PPDS
  • PA
    • Porto Alegre, PA, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre HCPA PPDS
  • PR
    • Curitiba, PR, Brazil, 81520-060
      • Recruiting
      • Hospital Erasto Gaertner
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20230-130
      • Recruiting
      • Instituto Nacional de Cancer
  • RS
    • Caxias Do Sul, RS, Brazil, 95070-561
      • Recruiting
      • Universidade de Caxias do Sul
    • Porto Alegre, RS, Brazil, 90610-000
      • Recruiting
      • Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
  • SP
    • Barretos, SP, Brazil, 14784-400
      • Recruiting
      • Hospital de Cancer de Barretos
    • Sao Jose Do Rio Preto, SP, Brazil, 15090-000
      • Recruiting
      • Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
    • Sao Paulo, SP, Brazil, 01246-000
      • Recruiting
      • Instituto do Cancer do Estado de Sao Paulo - ICESP
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Recruiting
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H2W 1S6
      • Recruiting
      • Jewish General Hospital; Sir Mortimer B. Davis
• Germany
  • Dresden, Germany, 01307
    • Withdrawn
    • Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden
• Hungary
  • Budapest, Hungary, 1088
    • Withdrawn
    • Semmelweis Egyetem
  • Gyongyos, Hungary, 3200
    • Recruiting
    • Clinexpert Kft. - Gyongyos
• Israel
  • Haifa, Israel, 3109601
    • Recruiting
    • Rambam Medical Center
  • Ramat-Gan, Israel, 5262000
    • Recruiting
    • Sheba Medical Center - PPDS
  • Tel Aviv, Israel, 6423906
    • Recruiting
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Completed
      • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
  • Lombardia
    • Milano, Lombardia, Italy, 20132
      • Recruiting
      • Irccs Ospedale San Raffaele;Oncologia Medica
    • Milano, Lombardia, Italy, 20162
      • Recruiting
      • ASST Grande Ospedale Metropolitano Niguarda
    • Rozzano (MI), Lombardia, Italy, 20089
      • Recruiting
      • Istituto Clinico Humanitas
  • Toscana
    • Pisa, Toscana, Italy, 56126
      • Recruiting
      • Azienda Ospedaliero Universitaria Pisana
• Kenya
  • Nairobi, Kenya, 00100
    • Recruiting
    • Aga Khan University Hospital
• Korea, Republic of
  • Seongnam-si, Korea, Republic of, 463-707
    • Recruiting
    • Seoul National University Bundang Hospital
  • Seoul, Korea, Republic of, 03080
    • Recruiting
    • Seoul National University Hospital
  • Seoul, Korea, Republic of, 05505
    • Recruiting
    • Asan Medical Center - PPDS
  • Seoul, Korea, Republic of, 06351
    • Recruiting
    • Samsung Medical Center - PPDS
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Recruiting
    • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
  • Leiden, Netherlands, 2333 ZA
    • Recruiting
    • Leids Universitair Medisch Centrum
  • Maastricht, Netherlands, 6229 HX
    • Recruiting
    • Maastricht University Medical Center
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Universitair Medisch Centrum Utrecht
• New Zealand
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital
  • Auckland, New Zealand, 1023
    • Recruiting
    • Auckland City Hospital, Cancer and Blood Research
  • Christchurch, New Zealand, 8011
    • Recruiting
    • New Zealand Clinical Research - Christchurch
• Norway
  • Bergen, Norway, 5053
    • Recruiting
    • Haukeland University Hospital; Hospital Pharmacy
  • Oslo, Norway, 0424
    • Recruiting
    • Oslo university hospital Radiumhospitalet
• Poland
  • Gdansk, Poland, 80-952
    • Recruiting
    • Medical University of Gdansk
  • Jozefow, Poland, 05-410
    • Recruiting
    • Biokinetica, Przychodnia Jozefow
  • Pozna?, Poland, 60-780
    • Recruiting
    • Uniwersytecki Szpital Kliniczny w Poznaniu
• Russian Federation
  • Tatarstan
    • Kazan, Tatarstan, Russian Federation, 420029
      • Withdrawn
      • Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
• Spain
  • Barcelona, Spain, 08035
    • Recruiting
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Recruiting
    • Hospital Universitario HM Sanchinarro-CIOCC
  • Malaga, Spain, 29010
    • Recruiting
    • Hospital Clinico Universitario Virgen de la Victoria
  • Sevilla, Spain, 41013
    • Recruiting
    • Hospital Universitario Virgen del Rocío
  • Valencia, Spain, 46010
    • Recruiting
    • Hospital Clínico Universitario de Valencia
• Switzerland
  • Basel, Switzerland, 4031
    • Withdrawn
    • Universitaetsspital Basel; Onkologie
  • Bern, Switzerland, 3010
    • Recruiting
    • Inselspital
  • Genève, Switzerland, 1211
    • Recruiting
    • Hopitaux Universitaires de Geneve
  • Zürich, Switzerland, 8091
    • Withdrawn
    • Unversitätsspital Zürich
• United Kingdom
  • Birmingham, United Kingdom, B15 2TH
    • Recruiting
    • Queen Elizabeth Hospital
  • Cardiff, United Kingdom, CF14 2TL
    • Recruiting
    • Velindre Cancer Centre
  • London, United Kingdom, W1T 7HA
    • Recruiting
    • University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • Recruiting
      • UCSD Moores Cancer Center
    • Orange, California, United States, 92868
      • Recruiting
      • Chao Family Comprehensive Cancer Center UCI
    • San Francisco, California, United States, 94115
      • Withdrawn
      • Univ of Calif, San Francisco; Breast Cancer Center
  • Connecticut
    • New Haven, Connecticut, United States, 06520
      • Recruiting
      • Yale Cancer Center
  • Florida
    • Sarasota, Florida, United States, 34232
      • Recruiting
      • Florida Cancer Specialists - Sarasota
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Recruiting
      • Dana Farber Cancer Institute
  • New York
    • New York, New York, United States, 11101
      • Recruiting
      • Memorial Sloan Kettering Cancer Center
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • Recruiting
      • University of Oklahoma; Stephenson Oklahoma Canc Ctr
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • Abramson Cancer Center; Univ of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15232
      • Recruiting
      • UPMC - Hillman Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

7

Arms and Interventions

Participant Group / 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, 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Adverse Events (AEs)	Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)	From Cycle 1 Day 1 until 28 days after the final dose (or as specified in the protocol). A cycle is 21 days.
Percentage of Participants With Dose-Limiting Toxicities (DLTs)		From Cycle 1 Day 1 through Day 21. A cycle is 21 days.

Secondary Outcome Measures

Outcome Measure	Time Frame
Plasma Concentrations of GDC-6036	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	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	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	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)	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	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	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])	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])	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])	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])	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	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.

Collaborators and Investigators

• Sponsor: Genentech, Inc.
• Investigators: Study Director: Clinical Trials, Genentech, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Estimated): November 30, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 24, 2020
• First Posted (Actual): June 29, 2020

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; Bevacizumab; Erlotinib; Atezolizumab; Colorectal Cancer; Cetuximab; SHP2; KRAS G12C; Metastatic Solid Tumor; GDC-1971; GDC-6036; Inavolisib
• Additional Relevant MeSH Terms: Digestive System Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Protein Kinase Inhibitors; Immune Checkpoint Inhibitors; Phosphoinositide-3 Kinase Inhibitors; Tyrosine Kinase Inhibitors; Erlotinib Hydrochloride; Bevacizumab; Cetuximab; Atezolizumab; Inavolisib
• Other Study ID Numbers: GO42144; 2020-000084-22 (EudraCT Number); 2023-506311-18-00 (Other Identifier: EU CT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD 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).

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No