Clinical trial NCT04449874: 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
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
Conditions: Non-Small Cell Lung Cancer
Colorectal Cancer
Advanced Solid Tumors
Keywords: KRAS G12C
Non-Small Cell Lung Cancer
Colorectal Cancer
GDC-6036
Metastatic Solid Tumor
Atezolizumab
Bevacizumab
Cetuximab
Erlotinib
Inavolisib
GDC-1971
SHP2
Lead sponsor: Genentech, Inc.
Sponsor class: INDUSTRY
First posted: 2020-06-29
Enrollment: 498
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Adverse Events (AEs)
timeFrame: From Cycle 1 Day 1 until 28 days after the final dose (or as specified in the protocol). A cycle is 21 days.
measure: Percentage of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: From Cycle 1 Day 1 through Day 21. A cycle is 21 days.
Secondary outcomes:
measure: Plasma Concentrations of GDC-6036
timeFrame: 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.
measure: Plasma Concentrations of Erlotinib
timeFrame: 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.
measure: Plasma Concentrations of GDC-1971
timeFrame: 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.
measure: Plasma Concentrations of Inavolisib
timeFrame: 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.
measure: Objective Response Rate (ORR) as Determined by the Investigator According to Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1)
timeFrame: 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.
measure: Duration of Response (DOR) as Determined by the Investigator According to RECIST v1.1
timeFrame: 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.
measure: Progression-free survival (PFS) as determined by the investigator according to RECIST v1.1
timeFrame: 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.
measure: Relationship Between GDC-6036 Exposure (Maximum Plasma Concentration Observed [Cmax])
timeFrame: 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.
measure: Relationship Between GDC-6036 Exposure (Time to Maximum Plasma Concentration [Tmax])
timeFrame: 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.
measure: Relationship Between GDC-6036 Exposure (Half-life [t1/2])
timeFrame: 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.
measure: Relationship Between GDC-6036 Exposure (Area Under the Curve [AUC])
timeFrame: 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.
measure: Relationship Between Tumor Pharmacodynamic Effects of GDC-6036
timeFrame: 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.
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope Comprehensive Cancer Center
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Orange
country: United States
facility: Chao Family Comprehensive Cancer Center UCI
state: California
city: San Francisco
country: United States
facility: Univ of Calif, San Francisco
state: California
city: New Haven
country: United States
facility: Yale Cancer Center
state: Connecticut
city: Sarasota
country: United States
facility: Florida Cancer Specialists - Sarasota
state: Florida
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC - Hillman Cancer Center
state: Pennsylvania
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital Sydney
state: New South Wales
city: Mount Kuring-gai
country: Australia
facility: Slade Health Inward goods
state: New South Wales
city: Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Melbourne
country: Australia
facility: Alfred Health
state: Victoria
city: Nedlands
country: Australia
facility: Linear Clinical Research Limited
state: Western Australia
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Liège
country: Belgium
facility: CHU de Liège
city: Mechelen
country: Belgium
facility: AZ St Maarten Campus Leopoldstr
city: Belo Horizonte
country: Brazil
facility: Santa Casa de Misericordia de Belo Horizonte - PPDS
state: Minas Gerais
city: Curitiba
country: Brazil
facility: Hospital Erasto Gaertner
state: Paraná
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre HCPA PPDS
state: Pará
city: Caxias Do Sul
country: Brazil
facility: Universidade de Caxias do Sul
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas Da Pontificia Universidade Catolica Do Rio Grande Do Sul (PUCRS)
state: Rio Grande Do Sul
city: Barretos
country: Brazil
facility: Hospital de Cancer de Barretos
state: São Paulo
city: Sao Jose Do Rio Preto
country: Brazil
facility: Fundacao Faculdade Regional de Medicina de Sao Jose Do Rio Preto Hospital de Base - PPDS
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Instituto do Cancer do Estado de Sao Paulo - ICESP
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Nacional de Câncer
city: Ottawa
country: Canada
facility: Ottawa Hospital
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Gyöngyös
country: Hungary
facility: Clinexpert Gyongyos Kft
city: Haifa
country: Israel
facility: Rambam Medical Center
city: Ramat Gan
country: Israel
facility: Sheba Medical Center - PPDS
city: Tel Aviv
country: Israel
facility: Tel-Aviv Sourasky Medical Center
city: Meldola
country: Italy
facility: Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori IRST - PPDS
state: Emilia-Romagna
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Asst Grande Ospedale Metropolitano Niguarda
state: Lombardia
city: Rozzano (MI)
country: Italy
facility: Istituto Clinico Humanitas
state: Lombardia
city: Pisa
country: Italy
facility: Azienda Ospedaliero Universitaria Pisana
state: Toscana
city: Nairobi
country: Kenya
facility: Aga Khan University Hospital
city: Seongnam-si
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center - PPDS
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center - PPDS
city: Amsterdam
country: Netherlands
facility: Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis
city: Leiden
country: Netherlands
facility: Leids Universitair Medisch Centrum
city: Maastricht
country: Netherlands
facility: Maastricht University Medical Center
city: Utrecht
country: Netherlands
facility: Universitair Medisch Centrum Utrecht
city: Auckland
country: New Zealand
facility: Auckland City Hospital, Cancer and Blood Research
city: Auckland
country: New Zealand
facility: Auckland City Hospital
city: Christchurch
country: New Zealand
facility: New Zealand Clinical Research - Christchurch
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Oslo
country: Norway
facility: Oslo university hospital Radiumhospitalet
city: Gdansk
country: Poland
facility: Uniwersyteckie Centrum Kliniczne, O?rodek Bada? Klinicznych Wczesnych Faz
city: Jozefow
country: Poland
facility: Biokinetica, Przychodnia Jozefow
city: Pozna?
country: Poland
facility: Uniwersytecki Szpital Kliniczny w Poznaniu
city: Kazan
country: Russian Federation
facility: Republican Clinical Oncology Dispensary of Ministry of Healthcare of Tatarstan Republic
state: Tatarstan
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron
city: Madrid
country: Spain
facility: START Madrid-FJD, Hospital Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario HM Sanchinarro-CIOCC
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocío
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Bern
country: Switzerland
facility: Inselspital
city: Genève
country: Switzerland
facility: Hôpitaux Universitaires de Genève
city: Zürich
country: Switzerland
facility: Unversitätsspital Zürich
city: Birmingham
country: United Kingdom
facility: Queen Elizabeth Hospital
city: Cardiff
country: United Kingdom
facility: Velindre Cancer Centre
city: London
country: United Kingdom
facility: University College London Hospitals NHS Foundation Trust
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
Study officials:
affiliation: Genentech, Inc.
name: Clinical Trials
role: STUDY_DIRECTOR
References: