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 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: GO421442020-000084-222023-506311-18-00
• Study Type: interventional
• Target: 498
• Locations: 17 countries
• Sites: 63

Brief Summary

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.

Conditions

Advanced Solid Tumors; Non-Small Cell Lung Cancer; Colorectal Cancer

Keywords

KRAS G12C; Non-Small Cell Lung Cancer; Colorectal Cancer; GDC-6036; Metastatic Solid Tumor; Atezolizumab; Bevacizumab; Cetuximab; Erlotinib; Inavolisib; GDC-1971; SHP2

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (12)

• 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.

Study Arms (7)

Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II)

EXPERIMENTAL

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

Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)

EXPERIMENTAL

Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab.

Drug: GDC-6036; Drug: Atezolizumab

Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)

EXPERIMENTAL

Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab.

Drug: GDC-6036; Drug: Cetuximab

Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)

EXPERIMENTAL

Participants with solid tumors will receive GDC-6036 in combination with bevacizumab.

Drug: GDC-6036; Drug: Bevacizumab

Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)

EXPERIMENTAL

Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib.

Drug: GDC-6036; Drug: Erlotinib

Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)

EXPERIMENTAL

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; Drug: GDC-1971

Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)

EXPERIMENTAL

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; Drug: Inavolisib

Interventions

GDC-6036 DRUG

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).

Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II); Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II); Arm C: GDC-6036 + Cetuximab (Stage I and Stage II); Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II); Arm E: GDC-6036 + Erlotinib (Stage I and Stage II); Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II); Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)

Atezolizumab DRUG

A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.

Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II)

Cetuximab DRUG

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.

Arm C: GDC-6036 + Cetuximab (Stage I and Stage II)

Bevacizumab DRUG

A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.

Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II)

Erlotinib DRUG

150 mg of erlotinib will be administered PO QD in 21 day cycles.

Arm E: GDC-6036 + Erlotinib (Stage I and Stage II)

GDC-1971 DRUG

The starting dose of GDC-1971 will be determined from its single-agent dose escalation.

Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II)

Inavolisib DRUG

The starting dose of inavolisib will be determined from its single-agent dose escalation.

Arm G: GDC-6036 + Inavolisib (Stage I and Stage II)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• Active brain metastases.
• Malabsorption or other condition that interferes with enteral absorption.
• Clinically significant cardiovascular dysfunction or liver disease.

Sponsors & Collaborators

• Genentech, Inc.: lead

Study Sites (63)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

UCSD Moores Cancer Center

La Jolla, California, 92093, United States

Location

Chao Family Comprehensive Cancer Center UCI

Orange, California, 92868, United States

Location

Yale Cancer Center

New Haven, Connecticut, 06511, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

University of Oklahoma

Oklahoma City, Oklahoma, 73104, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

UPMC - Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

St Vincent's Hospital Sydney

Darlinghurst, New South Wales, 2010, Australia

Location

Slade Health Inward goods

Mount Kuring-Gai, New South Wales, 2080, Australia

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Alfred Health

Melbourne, Victoria, 3004, Australia

Location

Linear Clinical Research Limited

Nedlands, Western Australia, 6009, Australia

Location

UZ Antwerpen

Edegem, 2650, Belgium

Location

CHU de Liège

Liège, 4000, Belgium

Location

AZ St Maarten Campus Leopoldstr

Mechelen, 2800, Belgium

Location

Santa Casa de Misericordia de Belo Horizonte - PPDS

Belo Horizonte, Minas Gerais, 30150-221, Brazil

Location

Hospital Erasto Gaertner

Curitiba, Paraná, 81520-060, Brazil

Location

Hospital de Clinicas de Porto Alegre HCPA PPDS

Pôrto Alegre, Pará, 90035-903, Brazil

Location

Universidade de Caxias do Sul

Caxias do Sul, Rio Grande do Sul, 95070-561, Brazil

Location

Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)

Porto Alegre, Rio Grande do Sul, 90610-000, Brazil

Location

Instituto Nacional de Câncer

Rio de Janeiro, 20230-130, Brazil

Location

Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 2M9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

Location

Clinexpert Gyongyos Kft

Gyöngyös, 3200, Hungary

Location

Rambam Medical Center

Haifa, 3109601, Israel

Location

Sheba Medical Center - PPDS

Ramat Gan, 52621, Israel

Location

Tel-Aviv Sourasky Medical Center

Tel Aviv, 6423906, Israel

Location

Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS

Meldola, Emilia-Romagna, 47014, Italy

Location

Irccs Ospedale San Raffaele

Milan, Lombardy, 20132, Italy

Location

Asst Grande Ospedale Metropolitano Niguarda

Milan, Lombardy, 20162, Italy

Location

Istituto Clinico Humanitas

Rozzano (MI), Lombardy, 20089, Italy

Location

Azienda Ospedaliero Universitaria Pisana

Pisa, Tuscany, 56100, Italy

Location

The Aga Khan University-Kenya.

Nairobi, 00100, Kenya

Location

Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis

Amsterdam, 1066 CX, Netherlands

Location

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Maastricht University Medical Center

Maastricht, 6229 HX, Netherlands

Location

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

Location

Auckland City Hospital, Cancer and Blood Research

Auckland, 1023, New Zealand

Location

Auckland City Hospital

Auckland, New Zealand

Location

New Zealand Clinical Research - Christchurch

Christchurch, New Zealand

Location

Haukeland University Hospital

Bergen, 5020, Norway

Location

Oslo university hospital Radiumhospitalet

Oslo, 0424, Norway

Location

Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz

Gdansk, 80-214, Poland

Location

Biokinetica, Przychodnia Jozefow

Józefów, 05-410, Poland

Location

Seoul National University Bundang Hospital

Seongnam-si, 13605, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Asan Medical Center - PPDS

Seoul, 05505, South Korea

Location

Samsung Medical Center - PPDS

Seoul, 06351, South Korea

Location

Hospital Universitari Vall d'Hebron

Barcelona, 08035, Spain

Location

START Madrid-FJD, Hospital Fundacion Jimenez Diaz

Madrid, 28040, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Universitario HM Sanchinarro-CIOCC

Madrid, 28050, Spain

Location

Hospital Clinico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

Location

Hospital Clinico Universitario de Valencia

Valencia, 46010, Spain

Location

Inselspital

Bern, 3010, Switzerland

Location

Hôpitaux Universitaires de Genève

Geneva, 1211, Switzerland

Location

Queen Elizabeth Hospital

Birmingham, B15 2GW, United Kingdom

Location

Velindre Cancer Centre

Cardiff, CF14 2TL, United Kingdom

Location

University College London Hospitals NHS Foundation Trust

London, W1T 7HA, United Kingdom

Location

The Christie NHS Foundation Trust

Manchester, M20 4BX, United Kingdom

Location

Related Publications (3)

• 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.

  PMID: 40632992 DERIVED

• 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.

  PMID: 38052910 DERIVED

• 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.

  PMID: 37611121 DERIVED

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis

Interventions

atezolizumab; Cetuximab; Bevacizumab; Erlotinib Hydrochloride; inavolisib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Clinical Trials

  Genentech, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: June 29, 2020
• Study Start: July 29, 2020
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (3); BE (3); KR (4); PL (2); NO (2); GB (4); CA (3); IT (5); IL (3); BR (6); HU (1); AU (5); KE (1); NL (4); CH (2); ES (7); US (8)