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
- Conditions
- Non-Small Cell Lung CancerAdvanced Solid TumorsColorectal Cancer
- Interventions
- Registration Number
- NCT04449874
- Lead Sponsor
- Genentech, Inc.
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 498
- 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.
- Active brain metastases.
- Malabsorption or other condition that interferes with enteral absorption.
- Clinically significant cardiovascular dysfunction or liver disease.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Arm A: Dose-escalation (Stage I), Dose Expansion (Stage II) GDC-6036 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. Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) GDC-6036 Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab. Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) Erlotinib Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib. Arm G: GDC-6036 + Inavolisib (Stage I and Stage II) GDC-6036 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. Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) GDC-6036 Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab. Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) GDC-6036 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. Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) GDC-6036 Participants with solid tumors will receive GDC-6036 in combination with bevacizumab. Arm E: GDC-6036 + Erlotinib (Stage I and Stage II) GDC-6036 Participants with non-small cell lung cancer will receive GDC-6036 in combination with erlotinib. Arm C: GDC-6036 + Cetuximab (Stage I and Stage II) Cetuximab Participants with colorectal cancer will receive GDC-6036 in combination with cetuximab. Arm B: GDC-6036 + Atezolizumab (Stage I and Stage II) Atezolizumab Participants with non-small cell lung cancer will receive GDC-6036 in combination with atezolizumab. Arm D: GDC-6036 + Bevacizumab (Stage I and Stage II) Bevacizumab Participants with solid tumors will receive GDC-6036 in combination with bevacizumab. Arm F: GDC-6036 + GDC-1971 (Stage I and Stage II) GDC-1971 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. Arm G: GDC-6036 + Inavolisib (Stage I and Stage II) Inavolisib 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.
- Primary Outcome Measures
Name Time Method Percentage of Participants With Dose-Limiting Toxicities (DLTs) From Cycle 1 Day 1 through Day 21. A cycle is 21 days. Percentage of Participants With Adverse Events (AEs) From Cycle 1 Day 1 until 28 days after the final dose (or as specified in the protocol). A cycle is 21 days. Severity is determined according to National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0)
- Secondary Outcome Measures
Name Time Method 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. 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. 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. 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. 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. 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. 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. 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. 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.
Trial Locations
- Locations (73)
Univ of Calif, San Francisco
🇺🇸San Francisco, California, United States
University of Oklahoma
🇺🇸Oklahoma City, Oklahoma, United States
Abramson Cancer Center
🇺🇸Philadelphia, Pennsylvania, United States
Jewish General Hospital
🇨🇦Montreal, Quebec, Canada
Semmelweis Egyetem
ðŸ‡ðŸ‡ºBudapest, Hungary
Irccs Ospedale San Raffaele
🇮🇹Milano, Lombardia, Italy
Haukeland University Hospital
🇳🇴Bergen, Norway
Universitaetsspital Basel
🇨ðŸ‡Basel, Switzerland
University College London Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
City of Hope Comprehensive Cancer Center
🇺🇸Duarte, California, United States
Chao Family Comprehensive Cancer Center UCI
🇺🇸Orange, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
Florida Cancer Specialists - Sarasota
🇺🇸Sarasota, Florida, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering Cancer Center
🇺🇸New York, New York, United States
UPMC - Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
St Vincent's Hospital Sydney
🇦🇺Darlinghurst, New South Wales, Australia
Slade Health Inward goods
🇦🇺Mount Kuring-gai, New South Wales, Australia
Peter MacCallum Cancer Center
🇦🇺Melbourne, Victoria, Australia
Alfred Health
🇦🇺Melbourne, Victoria, Australia
Linear Clinical Research Limited
🇦🇺Nedlands, Western Australia, Australia
UZ Antwerpen
🇧🇪Edegem, Belgium
CHU de Liège
🇧🇪Liège, Belgium
AZ St Maarten Campus Leopoldstr
🇧🇪Mechelen, Belgium
Santa Casa de Misericordia de Belo Horizonte - PPDS
🇧🇷Belo Horizonte, Minas Gerais, Brazil
Hospital Erasto Gaertner
🇧🇷Curitiba, Paraná, Brazil
Hospital de Clinicas de Porto Alegre HCPA PPDS
🇧🇷Porto Alegre, Pará, Brazil
Universidade de Caxias do Sul
🇧🇷Caxias Do Sul, Rio Grande Do Sul, Brazil
Instituto Nacional de Câncer
🇧🇷Rio de Janeiro, Brazil
Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
🇧🇷Porto Alegre, Rio Grande Do Sul, Brazil
Hospital de Cancer de Barretos
🇧🇷Barretos, São Paulo, Brazil
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
🇧🇷Sao Jose Do Rio Preto, São Paulo, Brazil
Instituto do Cancer do Estado de Sao Paulo - ICESP
🇧🇷Sao Paulo, São Paulo, Brazil
Ottawa Hospital
🇨🇦Ottawa, Ontario, Canada
Princess Margaret Cancer Centre
🇨🇦Toronto, Ontario, Canada
Asst Grande Ospedale Metropolitano Niguarda
🇮🇹Milano, Lombardia, Italy
Samsung Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Clinexpert Gyongyos Kft
ðŸ‡ðŸ‡ºGyöngyös, Hungary
Azienda Ospedaliero Universitaria Pisana
🇮🇹Pisa, Toscana, Italy
Rambam Medical Center
🇮🇱Haifa, Israel
Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
🇮🇹Meldola, Emilia-Romagna, Italy
Sheba Medical Center - PPDS
🇮🇱Ramat Gan, Israel
Tel-Aviv Sourasky Medical Center
🇮🇱Tel Aviv, Israel
Istituto Clinico Humanitas
🇮🇹Rozzano (MI), Lombardia, Italy
Aga Khan University Hospital
🇰🇪Nairobi, Kenya
Auckland City Hospital, Cancer and Blood Research
🇳🇿Auckland, New Zealand
Asan Medical Center - PPDS
🇰🇷Seoul, Korea, Republic of
Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
🇳🇱Amsterdam, Netherlands
Leids Universitair Medisch Centrum
🇳🇱Leiden, Netherlands
Universitair Medisch Centrum Utrecht
🇳🇱Utrecht, Netherlands
Auckland City Hospital
🇳🇿Auckland, New Zealand
New Zealand Clinical Research - Christchurch
🇳🇿Christchurch, New Zealand
Maastricht University Medical Center
🇳🇱Maastricht, Netherlands
Oslo university hospital Radiumhospitalet
🇳🇴Oslo, Norway
Medical University of Gdansk
🇵🇱Gdansk, Poland
Biokinetica, Przychodnia Jozefow
🇵🇱Jozefow, Poland
Uniwersytecki Szpital Kliniczny w Poznaniu
🇵🇱Pozna?, Poland
Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
🇷🇺Kazan, Tatarstan, Russian Federation
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain
START Madrid-FJD, Hospital Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario HM Sanchinarro-CIOCC
🇪🇸Madrid, Spain
Hospital Clinico Universitario Virgen de la Victoria
🇪🇸Malaga, Spain
Hospital Universitario Virgen del RocÃo
🇪🇸Sevilla, Spain
Hospital Clinico Universitario de Valencia
🇪🇸Valencia, Spain
Inselspital
🇨ðŸ‡Bern, Switzerland
Hôpitaux Universitaires de Genève
🇨ðŸ‡Genève, Switzerland
Unversitätsspital Zürich
🇨ðŸ‡Zürich, Switzerland
Queen Elizabeth Hospital
🇬🇧Birmingham, United Kingdom
Velindre Cancer Centre
🇬🇧Cardiff, United Kingdom
The Christie NHS Foundation Trust
🇬🇧Manchester, United Kingdom