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Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies

Primary Purpose

Non-Small Cell Lung Cancer

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
RMC-4630
Sotorasib
Sponsored by
Revolution Medicines, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-Small Cell Lung Cancer focused on measuring 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

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Florida Cancer Specialists
  • BRCR Medical Center Inc.
  • Cancer Specialists of North Florida
  • GenHarp Clinical Solutions
  • Hematology Oncology Clinic
  • New England Cancer Specialists
  • American Oncology Partners of Maryland, PA
  • Maryland Oncology Hematology, P.A.
  • Minnesota Oncology Hematology, P.A.
  • Nebraska Cancer Specialists
  • Comprehensive Cancer Centers of Nevada
  • New Jersey Center for Cancer Research
  • University of New Mexico Comprehensive Cancer Center
  • Roswell Park cancer Institute
  • Clinical Research Alliance, Inc.
  • Zangmeister Cancer Center
  • Charleston Oncology
  • Tennessee Oncology
  • Sarah Cannon Research Institute
  • CHRISTUS St. Michael-Colom and Carney Clinic P.A
  • Virginia Cancer Specialists
  • Virginia Oncology Associates
  • Northwest Cancer specialists, P.C.
  • South West Oncology
  • Blacktown Hospital
  • Goulburn Valley Health
  • Cross Cancer Institute
  • William Osler Health System
  • APHM Hopital Nord, Service d'Oncologie Multidisciplinaire et innovations therapeutics
  • Hospital Larrey Universite Paul Sabatier
  • Klinikum Esslingen GmbH
  • Asklepios Fachkliniken Munchen
  • Lungenklinik Hemer
  • Bethanien Hospital Moers
  • Comprehensive Cancer Center Mainfranken, University Wuerzburg
  • Lung Cancer Center, University of Saarland
  • POIS Sachsen GmbH
  • Charite Benjamin Franklin Comprehensive Cancer center
  • Evangelische Lung Clinic
  • Hamato-Onkologie Hamburg
  • Azienda Ospedaliera dei Colli
  • Azienda Sanitaria Ospedaliera S Luigi Gonzaga
  • Istituto Europeo Di Oncologia
  • Chungbuk National University Hospital
  • Seoul National University Hospital
  • Asan Medical Center
  • Samsung Medical Center
  • Hospital Universitario Virgen Macarena
  • Hospital Clinic de Barcelona
  • Complejo Hospitalario Universitario A Coruña
  • Clinica Universidad de Navarra
  • Clinica Universidad de Navarra
  • Hospital Universitario y Politecnico La Fe
  • Kaohsiung Medical University Chung Ho Memorial Hospital
  • E-DA Hospital
  • Taichung Veterans General Hospital
  • National Cheng Kung University Hospital
  • National Taiwan University Hospital
  • The Christie NHS Foundation Trust
  • The Royal Marsden NHS Foundation Trust

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

RMC-4630 and sotorasib, Safety Run-in

RMC-4630 and sotorasib, Expansion

Arm Description

Safety Run-In: RMC-4630 and sotorasib

Dose Expansion: RMC-4630 and sotorasib

Outcomes

Primary Outcome Measures

Objective response rate (ORR)
ORR as assessed per RECIST v1.1

Secondary Outcome Measures

Adverse Events
Number of Participants with Adverse Events
Serious Adverse Events
Number of Participants with Serious Adverse Events
Vital signs
Number of subjects with clinically significant changes in vital signs
Clinical laboratory test values
Number of subjects with clinically significant changes in clinical laboratory test values
ECGs Measurements
Number of subjects with clinically significant changes in ECGs Measurements
Concentration of RMC-4630
Trough Concentration of RMC-4630
Concentration of sotorasib
Trough Concentration of sotorasib
Duration of response (DOR)
DOR as assessed by RECIST v1.1
Disease Control Rate (DCR)
DCR as assessed by RECIST v1.1
Progression-free survival (PFS)
PFS as assessed by RECIST v1.1
Overall survival (OS)
Overall survival (OS)

Full Information

First Posted
September 14, 2021
Last Updated
March 30, 2023
Sponsor
Revolution Medicines, Inc.
Collaborators
Sanofi, Amgen
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1. Study Identification

Unique Protocol Identification Number
NCT05054725
Brief Title
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

2. Study Status

Record Verification Date
October 2022
Overall Recruitment Status
Active, not recruiting
Study Start Date
December 30, 2021 (Actual)
Primary Completion Date
September 30, 2023 (Anticipated)
Study Completion Date
March 3, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Revolution Medicines, Inc.
Collaborators
Sanofi, Amgen

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
47 (Actual)

8. Arms, Groups, and Interventions

Arm Title
RMC-4630 and sotorasib, Safety Run-in
Arm Type
Experimental
Arm Description
Safety Run-In: RMC-4630 and sotorasib
Arm Title
RMC-4630 and sotorasib, Expansion
Arm Type
Experimental
Arm Description
Dose Expansion: RMC-4630 and sotorasib
Intervention Type
Drug
Intervention Name(s)
RMC-4630
Other Intervention Name(s)
SAR442720
Intervention Description
RMC-4630 administered orally as a capsule
Intervention Type
Drug
Intervention Name(s)
Sotorasib
Other Intervention Name(s)
AMG 510, Lumakras
Intervention Description
Sotorasib administered orally as a tablet
Primary Outcome Measure Information:
Title
Objective response rate (ORR)
Description
ORR as assessed per RECIST v1.1
Time Frame
approximately 12 months
Secondary Outcome Measure Information:
Title
Adverse Events
Description
Number of Participants with Adverse Events
Time Frame
approximately 12 months
Title
Serious Adverse Events
Description
Number of Participants with Serious Adverse Events
Time Frame
approximately 12 months
Title
Vital signs
Description
Number of subjects with clinically significant changes in vital signs
Time Frame
approximately 12 months
Title
Clinical laboratory test values
Description
Number of subjects with clinically significant changes in clinical laboratory test values
Time Frame
approximately 12 months
Title
ECGs Measurements
Description
Number of subjects with clinically significant changes in ECGs Measurements
Time Frame
approximately 12 months
Title
Concentration of RMC-4630
Description
Trough Concentration of RMC-4630
Time Frame
approximately 12 months
Title
Concentration of sotorasib
Description
Trough Concentration of sotorasib
Time Frame
approximately 12 months
Title
Duration of response (DOR)
Description
DOR as assessed by RECIST v1.1
Time Frame
approximately 12 months
Title
Disease Control Rate (DCR)
Description
DCR as assessed by RECIST v1.1
Time Frame
approximately 12 months
Title
Progression-free survival (PFS)
Description
PFS as assessed by RECIST v1.1
Time Frame
approximately 12 months
Title
Overall survival (OS)
Description
Overall survival (OS)
Time Frame
approximately 12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Revolution Medicines, Inc.
Organizational Affiliation
Revolution Medicines, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Florida Cancer Specialists
City
Fort Myers
State/Province
Florida
ZIP/Postal Code
33901
Country
United States
Facility Name
BRCR Medical Center Inc.
City
Plantation
State/Province
Florida
ZIP/Postal Code
33322
Country
United States
Facility Name
Cancer Specialists of North Florida
City
Saint Augustine
State/Province
Florida
ZIP/Postal Code
32086
Country
United States
Facility Name
GenHarp Clinical Solutions
City
Evergreen Park
State/Province
Illinois
ZIP/Postal Code
60805
Country
United States
Facility Name
Hematology Oncology Clinic
City
Baton Rouge
State/Province
Louisiana
ZIP/Postal Code
70809
Country
United States
Facility Name
New England Cancer Specialists
City
Scarborough
State/Province
Maine
ZIP/Postal Code
04074
Country
United States
Facility Name
American Oncology Partners of Maryland, PA
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Facility Name
Maryland Oncology Hematology, P.A.
City
Columbia
State/Province
Maryland
ZIP/Postal Code
21044
Country
United States
Facility Name
Minnesota Oncology Hematology, P.A.
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Facility Name
Nebraska Cancer Specialists
City
Omaha
State/Province
Nebraska
ZIP/Postal Code
68130
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89169
Country
United States
Facility Name
New Jersey Center for Cancer Research
City
Brick
State/Province
New Jersey
ZIP/Postal Code
08724
Country
United States
Facility Name
University of New Mexico Comprehensive Cancer Center
City
Albuquerque
State/Province
New Mexico
ZIP/Postal Code
87131
Country
United States
Facility Name
Roswell Park cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Facility Name
Clinical Research Alliance, Inc.
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
Zangmeister Cancer Center
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43219
Country
United States
Facility Name
Charleston Oncology
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29414
Country
United States
Facility Name
Tennessee Oncology
City
Chattanooga
State/Province
Tennessee
ZIP/Postal Code
37404
Country
United States
Facility Name
Sarah Cannon Research Institute
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Facility Name
CHRISTUS St. Michael-Colom and Carney Clinic P.A
City
Texarkana
State/Province
Texas
ZIP/Postal Code
75503
Country
United States
Facility Name
Virginia Cancer Specialists
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Northwest Cancer specialists, P.C.
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States
Facility Name
South West Oncology
City
Warrnambool
State/Province
Victoria
ZIP/Postal Code
3280
Country
Australia
Facility Name
Blacktown Hospital
City
Blacktown
ZIP/Postal Code
2148
Country
Australia
Facility Name
Goulburn Valley Health
City
Shepparton
ZIP/Postal Code
3630
Country
Australia
Facility Name
Cross Cancer Institute
City
Edmonton
State/Province
Alberta
ZIP/Postal Code
T6G 1Z2
Country
Canada
Facility Name
William Osler Health System
City
Mississauga
State/Province
Ontario
ZIP/Postal Code
L5N 5M8
Country
Canada
Facility Name
APHM Hopital Nord, Service d'Oncologie Multidisciplinaire et innovations therapeutics
City
Marseille
ZIP/Postal Code
13015
Country
France
Facility Name
Hospital Larrey Universite Paul Sabatier
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Klinikum Esslingen GmbH
City
Esslingen
State/Province
Baden-Wurttemberg
ZIP/Postal Code
73730
Country
Germany
Facility Name
Asklepios Fachkliniken Munchen
City
Gauting
State/Province
Bavaria
ZIP/Postal Code
82131
Country
Germany
Facility Name
Lungenklinik Hemer
City
Hemer
State/Province
North Rhine- Westphalia
ZIP/Postal Code
58675
Country
Germany
Facility Name
Bethanien Hospital Moers
City
Moers
State/Province
North Rhine-Westphalia
ZIP/Postal Code
47441
Country
Germany
Facility Name
Comprehensive Cancer Center Mainfranken, University Wuerzburg
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
Facility Name
Lung Cancer Center, University of Saarland
City
Homburg
State/Province
Saarland
ZIP/Postal Code
66421
Country
Germany
Facility Name
POIS Sachsen GmbH
City
Leipzig
State/Province
Sachsen
ZIP/Postal Code
04347
Country
Germany
Facility Name
Charite Benjamin Franklin Comprehensive Cancer center
City
Berlin
ZIP/Postal Code
12200
Country
Germany
Facility Name
Evangelische Lung Clinic
City
Berlin
ZIP/Postal Code
13125
Country
Germany
Facility Name
Hamato-Onkologie Hamburg
City
Hamburg
ZIP/Postal Code
20251
Country
Germany
Facility Name
Azienda Ospedaliera dei Colli
City
Napoli
State/Province
Campania
ZIP/Postal Code
80131
Country
Italy
Facility Name
Azienda Sanitaria Ospedaliera S Luigi Gonzaga
City
Orbassano
State/Province
Piedmont
ZIP/Postal Code
10043
Country
Italy
Facility Name
Istituto Europeo Di Oncologia
City
Milano
ZIP/Postal Code
20141
Country
Italy
Facility Name
Chungbuk National University Hospital
City
Cheongju-si
ZIP/Postal Code
28644
Country
Korea, Republic of
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
03080
Country
Korea, Republic of
Facility Name
Asan Medical Center
City
Seoul
ZIP/Postal Code
05505
Country
Korea, Republic of
Facility Name
Samsung Medical Center
City
Seoul
ZIP/Postal Code
06351
Country
Korea, Republic of
Facility Name
Hospital Universitario Virgen Macarena
City
Sevilla
State/Province
Andalucia
ZIP/Postal Code
41009
Country
Spain
Facility Name
Hospital Clinic de Barcelona
City
Barcelona
State/Province
Catalonia
ZIP/Postal Code
08036
Country
Spain
Facility Name
Complejo Hospitalario Universitario A Coruña
City
A Coruña
State/Province
Galicia
ZIP/Postal Code
15006
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Pamplona
State/Province
Navarra
ZIP/Postal Code
31008
Country
Spain
Facility Name
Clinica Universidad de Navarra
City
Madrid
ZIP/Postal Code
28027
Country
Spain
Facility Name
Hospital Universitario y Politecnico La Fe
City
Valencia
ZIP/Postal Code
46026
Country
Spain
Facility Name
Kaohsiung Medical University Chung Ho Memorial Hospital
City
Kaohsiung
ZIP/Postal Code
807
Country
Taiwan
Facility Name
E-DA Hospital
City
Kaohsiung
ZIP/Postal Code
824
Country
Taiwan
Facility Name
Taichung Veterans General Hospital
City
Taichung
ZIP/Postal Code
40705
Country
Taiwan
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
704
Country
Taiwan
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Facility Name
The Christie NHS Foundation Trust
City
Manchester
State/Province
Greater Manchester
ZIP/Postal Code
M20 4BX
Country
United Kingdom
Facility Name
The Royal Marsden NHS Foundation Trust
City
Sutton
State/Province
Surrey
ZIP/Postal Code
SM2 5PT
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Combination Study of RMC-4630 and Sotorasib for NSCLC Subjects With KRASG12C Mutation After Failure of Prior Standard Therapies

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