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: Active, not 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 Locations

• Australia
  • New South Wales
    • Darlinghurst, New South Wales, Australia, 2010
      • St Vincent's Hospital Sydney
    • Mount Kuring-Gai, New South Wales, Australia, 2080
      • Slade Health Inward goods
  • Victoria
    • Melbourne, Victoria, Australia, 3004
      • Alfred Health
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Center
  • Western Australia
    • Nedlands, Western Australia, Australia, 6009
      • Linear Clinical Research Limited
• Belgium
  • Edegem, Belgium, 2650
    • UZ Antwerpen
  • Liège, Belgium, 4000
    • CHU de Liege
  • Mechelen, Belgium, 2800
    • AZ St Maarten Campus Leopoldstr
• Brazil
  • Rio de Janeiro, Brazil, 20230-130
    • Instituto Nacional de Cancer
  • Minas Gerais
    • Belo Horizonte, Minas Gerais, Brazil, 30150-221
      • Santa Casa de Misericordia de Belo Horizonte - PPDS
  • Paraná
    • Curitiba, Paraná, Brazil, 81520-060
      • Hospital Erasto Gaertner
  • Pará
    • Pôrto Alegre, Pará, Brazil, 90035-903
      • Hospital de Clinicas de Porto Alegre HCPA PPDS
  • Rio Grande do Sul
    • Caxias do Sul, Rio Grande do Sul, Brazil, 95070-561
      • Universidade de Caxias do sul
    • Porto Alegre, Rio Grande do Sul, Brazil, 90610-000
      • Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
• Canada
  • Ontario
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital
    • Toronto, Ontario, Canada, M5G 2M9
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Jewish General Hospital
• Hungary
  • Gyöngyös, Hungary, 3200
    • Clinexpert Gyongyos Kft
• Israel
  • Haifa, Israel, 3109601
    • Rambam Medical Center
  • Ramat Gan, Israel, 52621
    • Sheba Medical Center - PPDS
  • Tel Aviv, Israel, 6423906
    • Tel-Aviv Sourasky Medical Center
• Italy
  • Emilia-Romagna
    • Meldola, Emilia-Romagna, Italy, 47014
      • Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
  • Lombardy
    • Milan, Lombardy, Italy, 20132
      • IRCCS Ospedale San Raffaele
    • Milan, Lombardy, Italy, 20162
      • ASST Grande Ospedale Metropolitano Niguarda
    • Rozzano (MI), Lombardy, Italy, 20089
      • Istituto Clinico Humanitas
  • Tuscany
    • Pisa, Tuscany, Italy, 56100
      • Azienda Ospedaliero Universitaria Pisana
• Kenya
  • Nairobi, Kenya, 00100
    • The Aga Khan University-Kenya.
• Netherlands
  • Amsterdam, Netherlands, 1066 CX
    • Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
  • Leiden, Netherlands, 2333 ZA
    • Leids Universitair Medisch Centrum
  • Maastricht, Netherlands, 6229 HX
    • Maastricht University Medical Center
  • Utrecht, Netherlands, 3584 CX
    • Universitair Medisch Centrum Utrecht
• New Zealand
  • Auckland, New Zealand
    • Auckland City Hospital
  • Auckland, New Zealand, 1023
    • Auckland City Hospital, Cancer and Blood Research
  • Christchurch, New Zealand
    • New Zealand Clinical Research - Christchurch
• Norway
  • Bergen, Norway, 5020
    • Haukeland University Hospital
  • Oslo, Norway, 0424
    • Oslo university hospital Radiumhospitalet
• Poland
  • Gdansk, Poland, 80-214
    • Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz
  • Józefów, Poland, 05-410
    • Biokinetica, Przychodnia Jozefow
• South Korea
  • Seongnam-si, South Korea, 13605
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 03080
    • Seoul National University Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center - PPDS
  • Seoul, South Korea, 06351
    • Samsung Medical Center - PPDS
• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • START Madrid-FJD, Hospital Fundacion Jimenez Diaz
  • Madrid, Spain, 28050
    • Hospital Universitario HM Sanchinarro-CIOCC
  • Málaga, Spain, 29010
    • Hospital Clinico Universitario Virgen de la Victoria
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Valencia, Spain, 46010
    • Hospital Clinico Universitario de Valencia
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital
  • Geneva, Switzerland, 1211
    • Hopitaux Universitaires de Geneve
• United Kingdom
  • Birmingham, United Kingdom, B15 2GW
    • Queen Elizabeth Hospital
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre Cancer Centre
  • London, United Kingdom, W1T 7HA
    • University College London Hospitals NHS Foundation Trust
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope Comprehensive Cancer Center
    • La Jolla, California, United States, 92093
      • UCSD Moores Cancer Center
    • Orange, California, United States, 92868
      • Chao Family Comprehensive Cancer Center UCI
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Dana Farber Cancer Institute
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Abramson Cancer Center
    • Pittsburgh, Pennsylvania, United States, 15232
      • 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.

Publications and helpful links

General Publications

• Desai J, Alonso G, Kim SH, Cervantes A, Karasic T, Medina L, Shacham-Shmueli E, Cosman R, Falcon A, Gort E, Guren T, Massarelli E, Miller WH Jr, Paz-Ares L, Prenen H, Amatu A, Cremolini C, Kim TW, Moreno V, Ou SI, Passardi A, Sacher A, Santoro A, Stec R, Ulahannan S, Arbour K, Lorusso P, Luo J, Patel MR, Choi Y, Shi Z, Mandlekar S, Lin MT, Royer-Joo S, Chang J, Jun T, Dharia NV, Schutzman JL; GO42144 Investigator and Study Group; Han SW. Divarasib plus cetuximab in KRAS G12C-positive colorectal cancer: a phase 1b trial. Nat Med. 2024 Jan;30(1):271-278. doi: 10.1038/s41591-023-02696-8. Epub 2023 Dec 5.
• Sacher A, LoRusso P, Patel MR, Miller WH Jr, Garralda E, Forster MD, Santoro A, Falcon A, Kim TW, Paz-Ares L, Bowyer S, de Miguel M, Han SW, Krebs MG, Lee JS, Cheng ML, Arbour K, Massarelli E, Choi Y, Shi Z, Mandlekar S, Lin MT, Royer-Joo S, Chang J, Dharia NV, Schutzman JL, Desai J; GO42144 Investigator and Study Group. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. N Engl J Med. 2023 Aug 24;389(8):710-721. doi: 10.1056/NEJMoa2303810.
• Sacher AG, Miller WH Jr, Patel MR, Paz-Ares L, Santoro A, Ahn MJ, Dziadziuszko R, Freres P, Luo J, Bowyer S, Desai J, Markman B, De Miguel M, Deva S, Falcon A, Alonso G, Guedes JD, Kim SH, Krebs MG, Laurie SA, Massarelli E, Medina L, Prenen H, Amatu A, Van Dongen M, Choi Y, Hou X, Qi T, Lin MT, Koli K, Mayo MC, Yau KK, Royer-Joo S, Chang J, Jun T, Dharia NV, Schutzman JL, Lorusso P; GO42144 Investigator Study group; GO42144 Investigator Study Group. Single-Agent Divarasib in Patients With KRAS G12C-Positive Non-Small Cell Lung Cancer: Long-Term Follow-Up of a Phase I Study. J Clin Oncol. 2025 Oct 20;43(30):3249-3253. doi: 10.1200/JCO-25-00040. Epub 2025 Jul 9.

Study record dates

Study Major Dates

• Study Start (Actual): July 29, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

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): February 12, 2026
• Last Update Submitted That Met QC Criteria: February 11, 2026
• Last Verified: February 1, 2026

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: Pathologic Processes; Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Neoplastic Processes; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Pathological Conditions, Signs and Symptoms; Colorectal Neoplasms; Neoplasm Metastasis; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Quinazolines; 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