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

Colorectal Cancer Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04449874
• Other study ID #: GO42144
• Secondary ID: 2020-000084-2220
• Status: Recruiting
• Phase: Phase 1
• Start date: July 29, 2020
• Est. completion date: November 30, 2024

Study information

• Verified date: June 2024
• Source: Genentech, Inc.
• Contact: Reference Study ID Number: GO42144 whttps://forpatients.roche.co
• Phone: 888-662-6728 (U.S. and Canada)
• Email: global-roche-genentech-trials[@]gene.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 498
• Est. completion date: November 30, 2024
• Est. primary completion date: November 30, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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).
• Atezolizumab
A 1200 milligram (mg) intravenous (IV) infusion of atezolizumab will be administered on Day 1 of 21 day cycles.
• 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.
• Bevacizumab
A 15 milligram per kilogram (mg/kg) IV infusion of bevacizumab will be administered on Day 1 of 21 day cycles.
• Erlotinib
150 mg of erlotinib will be administered PO QD in 21 day cycles.
• GDC-1971
The starting dose of GDC-1971 will be determined from its single-agent dose escalation.
• Inavolisib
The starting dose of inavolisib will be determined from its single-agent dose escalation.

Locations

Country	Name	City	State
Australia	St Vincent's Hospital Sydney	Darlinghurst	New South Wales
Australia	Alfred Health	Melbourne	Victoria
Australia	Slade Health Inward goods	Mount Kuring-gai	New South Wales
Australia	Linear Clinical Research Limited	Nedlands	Western Australia
Australia	Peter MacCallum Cancer Center	North Melbourne	Victoria
Belgium	UZ Antwerpen	Edegem
Belgium	CHU de Liège	Liège
Belgium	AZ St Maarten Campus Leopoldstr	Mechelen
Brazil	Hospital de Cancer de Barretos	Barretos	SP
Brazil	Santa Casa de Misericordia de Belo Horizonte - PPDS	Belo Horizonte	MG
Brazil	Universidade de Caxias do Sul	Caxias Do Sul	RS
Brazil	Hospital Erasto Gaertner	Curitiba	PR
Brazil	Hospital de Clinicas de Porto Alegre HCPA PPDS	Porto Alegre	PA
Brazil	Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)	Porto Alegre	RS
Brazil	Instituto Nacional de Câncer	Rio de Janeiro	RJ
Brazil	Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS	Sao Jose Do Rio Preto	SP
Brazil	Instituto do Cancer do Estado de Sao Paulo - ICESP	Sao Paulo	SP
Canada	Jewish General Hospital; Sir Mortimer B. Davis	Montreal	Quebec
Canada	Ottawa Hospital	Ottawa	Ontario
Canada	Princess Margaret Cancer Centre	Toronto	Ontario
Germany	Universitätsklinikum "Carl Gustav Carus" der Technischen Universität Dresden	Dresden
Hungary	Semmelweis Egyetem; Belgyogyaszati es Hematologiai Klinika	Budapest
Hungary	Clinexpert Kft. - Gyongyos	Gyongyos
Israel	Rambam Medical Center	Haifa
Israel	Sheba Medical Center - PPDS	Ramat Gan
Israel	Tel-Aviv Sourasky Medical Center	Tel Aviv
Italy	Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS	Meldola	Emilia-Romagna
Italy	Asst Grande Ospedale Metropolitano Niguarda	Milano	Lombardia
Italy	Irccs Ospedale San Raffaele;Oncologia Medica	Milano	Lombardia
Italy	Azienda Ospedaliero Universitaria Pisana	Pisa	Toscana
Italy	Istituto Clinico Humanitas	Rozzano (MI)	Lombardia
Kenya	Aga Khan University Hospital	Nairobi
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam-si
Korea, Republic of	Asan Medical Center - PPDS	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	Leids Universitair Medisch Centrum	Leiden
Netherlands	Maastricht University Medical Center	Maastricht
Netherlands	Universitair Medisch Centrum Utrecht	Utrecht
New Zealand	Auckland City Hospital	Auckland
New Zealand	Auckland City Hospital, Cancer and Blood Research	Auckland
New Zealand	New Zealand Clinical Research - Christchurch	Christchurch
Norway	Haukeland University Hospital; Hospital Pharmacy	Bergen
Norway	Oslo university hospital Radiumhospitalet	Oslo
Poland	Medical University of Gdansk	Gdansk
Poland	Biokinetica, Przychodnia Jozefow	Jozefow
Poland	Uniwersytecki Szpital Kliniczny w Poznaniu	Pozna?
Russian Federation	Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic	Kazan	Tatarstan
Spain	Hospital Universitari Vall d'Hebron	Barcelona
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario HM Sanchinarro-CIOCC	Madrid
Spain	START Madrid-FJD, Hospital Fundacion Jimenez Diaz	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria	Malaga
Spain	Hospital Universitario Virgen del Rocío	Sevilla
Spain	Hospital Clinico Universitario de Valencia	Valencia
Switzerland	Universitaetsspital Basel; Onkologie	Basel
Switzerland	Inselspital	Bern
Switzerland	Hôpitaux Universitaires de Genève	Genève
Switzerland	Unversitätsspital Zürich	Zürich
United Kingdom	Queen Elizabeth Hospital	Birmingham
United Kingdom	Velindre Cancer Centre	Cardiff
United Kingdom	University College London Hospitals NHS Foundation Trust; NIHR UCLH Clinical Research Facility	London
United Kingdom	The Christie NHS Foundation Trust	Manchester
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	City of Hope Comprehensive Cancer Center	Duarte	California
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Yale Cancer Center	New Haven	Connecticut
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	University of Oklahoma; Stephenson Oklahoma Canc Ctr	Oklahoma City	Oklahoma
United States	Chao Family Comprehensive Cancer Center UCI	Orange	California
United States	Abramson Cancer Center; Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	UPMC - Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Univ of Calif, San Francisco; Breast Cancer Center	San Francisco	California
United States	Florida Cancer Specialists - Sarasota	Sarasota	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Genentech, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Brazil,  Canada,  Germany,  Hungary,  Israel,  Italy,  Kenya,  Korea, Republic of,  Netherlands,  New Zealand,  Norway,  Poland,  Russian Federation,  Spain,  Switzerland,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.
Primary	Percentage of Participants With Dose-Limiting Toxicities (DLTs)		From Cycle 1 Day 1 through Day 21. A cycle is 21 days.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.
Secondary	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.