Clinical trial NCT05054725: Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies
Official title: A Phase 2, Open-Label, Multicenter Study of the Combination of RMC-4630 and Sotorasib for Non-Small Cell Lung Cancer Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Non-Small Cell Lung Cancer
Keywords: SHP2
NSCLC
KRAS G12C
BRAF Class 1/2/unclassified
KRAS amplification
KRAS mutation
STK11/LKB1
KEAP1
PIK3CA
ATRX
BRCA2
carcinoma, non-small lung cancer
bronchial neoplasms
lung neoplasms
respiratory tract neoplasms
neoplasms by site
neoplasms
lung diseases
respiratory tract diseases
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
name: Amgen
First posted: 2021-09-23
Enrollment: 47
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: The purpose of this study is to evaluate the antitumor effects of sotorasib and RMC-4630 in subjects with KRASG12C mutant NSCLC

Detailed description: This is a phase 2 multicenter, open-label study evaluating the efficacy, safety, tolerability, and pharmacokinetics (PK) of RMC-4630 in combination with sotorasib in subjects with KRASG12C mutant NSCLC after failure of prior standard therapies.

Eligibility criteria: Inclusion Criteria:

* Subject must be ≥18 years of age.
* Subject must have pathologically documented, locally advanced or metastatic KRASG12C NSCLC (not amenable to curative surgery) that has progressed on prior standard therapies (no more than 3 prior lines of therapies are allowed)

Exclusion Criteria

* Primary central nervous system (CNS) tumors
* Known or suspected leptomeningeal or brain metastases or spinal cord compression
* Clinically significant cardiac disease
* Known impairment of GI function that would alter the absorption
* Active autoimmune disease requiring systemic treatment within past 2 years
* History of severe allergic reactions to any of the study intervention components
* Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
* Prior therapy with KRASG12C inhibitor and/or SHP2 inhibitor

Primary outcomes:
measure: Objective response rate (ORR)
timeFrame: approximately 12 months
Secondary outcomes:
measure: Adverse Events
timeFrame: approximately 12 months
measure: Serious Adverse Events
timeFrame: approximately 12 months
measure: Vital signs
timeFrame: approximately 12 months
measure: Clinical laboratory test values
timeFrame: approximately 12 months
measure: ECGs Measurements
timeFrame: approximately 12 months
measure: Concentration of RMC-4630
timeFrame: approximately 12 months
measure: Concentration of sotorasib
timeFrame: approximately 12 months
measure: Duration of response (DOR)
timeFrame: approximately 12 months
measure: Disease Control Rate (DCR)
timeFrame: approximately 12 months
measure: Progression-free survival (PFS)
timeFrame: approximately 12 months
measure: Overall survival (OS)
timeFrame: approximately 12 months
Other outcomes:
Locations:
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Plantation
country: United States
facility: BRCR Medical Center Inc.
state: Florida
city: Saint Augustine
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Evergreen Park
country: United States
facility: GenHarp Clinical Solutions
state: Illinois
city: Baton Rouge
country: United States
facility: Hematology Oncology Clinic
state: Louisiana
city: Scarborough
country: United States
facility: New England Cancer Specialists
state: Maine
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Columbia
country: United States
facility: Maryland Oncology Hematology, P.A.
state: Maryland
city: Minneapolis
country: United States
facility: Minnesota Oncology Hematology, P.A.
state: Minnesota
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Brick
country: United States
facility: New Jersey Center for Cancer Research
state: New Jersey
city: Albuquerque
country: United States
facility: University of New Mexico Comprehensive Cancer Center
state: New Mexico
city: Buffalo
country: United States
facility: Roswell Park cancer Institute
state: New York
city: New York
country: United States
facility: Clinical Research Alliance, Inc.
state: New York
city: Columbus
country: United States
facility: Zangmeister Cancer Center
state: Ohio
city: Charleston
country: United States
facility: Charleston Oncology
state: South Carolina
city: Chattanooga
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Texarkana
country: United States
facility: CHRISTUS St. Michael-Colom and Carney Clinic P.A
state: Texas
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
city: Norfolk
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Vancouver
country: United States
facility: Northwest Cancer specialists, P.C.
state: Washington
city: Warrnambool
country: Australia
facility: South West Oncology
state: Victoria
city: Blacktown
country: Australia
facility: Blacktown Hospital
city: Shepparton
country: Australia
facility: Goulburn Valley Health
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: Mississauga
country: Canada
facility: William Osler Health System
state: Ontario
city: Marseille
country: France
facility: APHM Hopital Nord, Service d'Oncologie Multidisciplinaire et innovations therapeutics
city: Toulouse
country: France
facility: Hospital Larrey Universite Paul Sabatier
city: Esslingen
country: Germany
facility: Klinikum Esslingen GmbH
state: Baden-Wurttemberg
city: Gauting
country: Germany
facility: Asklepios Fachkliniken Munchen
state: Bavaria
city: Hemer
country: Germany
facility: Lungenklinik Hemer
state: North Rhine- Westphalia
city: Moers
country: Germany
facility: Bethanien Hospital Moers
state: North Rhine-Westphalia
city: Homburg
country: Germany
facility: Comprehensive Cancer Center Mainfranken, University Wuerzburg
state: Saarland
city: Homburg
country: Germany
facility: Lung Cancer Center, University of Saarland
state: Saarland
city: Leipzig
country: Germany
facility: POIS Sachsen GmbH
state: Sachsen
city: Berlin
country: Germany
facility: Charite Benjamin Franklin Comprehensive Cancer center
city: Berlin
country: Germany
facility: Evangelische Lung Clinic
city: Hamburg
country: Germany
facility: Hamato-Onkologie Hamburg
city: Napoli
country: Italy
facility: Azienda Ospedaliera dei Colli
state: Campania
city: Orbassano
country: Italy
facility: Azienda Sanitaria Ospedaliera S Luigi Gonzaga
state: Piedmont
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
city: Cheongju-si
country: Korea, Republic of
facility: Chungbuk National University Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
state: Andalucia
city: Barcelona
country: Spain
facility: Hospital Clinic de Barcelona
state: Catalonia
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
state: Galicia
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarra
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Valencia
country: Spain
facility: Hospital Universitario y Politecnico La Fe
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical University Chung Ho Memorial Hospital
city: Kaohsiung
country: Taiwan
facility: E-DA Hospital
city: Taichung
country: Taiwan
facility: Taichung Veterans General Hospital
city: Tainan
country: Taiwan
facility: National Cheng Kung University Hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Manchester
country: United Kingdom
facility: The Christie NHS Foundation Trust
state: Greater Manchester
city: Sutton
country: United Kingdom
facility: The Royal Marsden NHS Foundation Trust
state: Surrey
Study officials:
affiliation: Revolution Medicines, Inc.
name: Revolution Medicines, Inc.
role: STUDY_DIRECTOR
References: