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Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Primary Purpose

Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma

Status
Recruiting
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
RMC-6291
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 (NSCLC) focused on measuring RMC-6291, RAS(ON), KRAS, KRASG12C, KRASG12C(ON), Targeted therapy, Metastatic cancer, Lung Cancer, Lung Neoplasms, Thoracic Neoplasms, Non-small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, NSCLC, Colorectal Cancer, Colonic Neoplasms, CRC, Appendiceal Cancer, KRAS mutation, STK11/LKB1, KEAP1, bronchial neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, Colon Cancer, Rectal Cancer, lung disease, respiratory tract diseases, Pancreatic Cancer, Carcinoma, Pancreatic Ductal, PDAC, Gastrointestinal Neoplasms, Intestinal Neoplasms, Esophageal cancer, Ampullary cancer, Gastric Cancer, Gynecological Cancer, Ovarian Cancer, Endometrial Cancer

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-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
  • ECOG performance status 0 or 1
  • Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation
  • Adequate organ function

Exclusion Criteria:

  • Primary central nervous system (CNS) tumors
  • Active brain metastases
  • Known impairment of GI function that would alter the absorption
  • Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.
  • Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Sites / Locations

  • Highlands Oncology GroupRecruiting
  • UC Irvine Cancer CenterRecruiting
  • UC Davis Cancer CenterRecruiting
  • UCSFRecruiting
  • University of Miami School of Medicine Sylvester Comprehensive Cancer CenterRecruiting
  • Moffitt Cancer CenterRecruiting
  • American Oncology Partners of MarylandRecruiting
  • Dana-Farber Cancer InstituteRecruiting
  • Roswell Park Comprehensive Cancer CenterRecruiting
  • MSK Cancer CenterRecruiting
  • Columbia University Irving Medical CenterRecruiting
  • Tennessee OncologyRecruiting
  • Next OncologyRecruiting
  • STARTRecruiting
  • Next Oncology VirginiaRecruiting
  • Southside Cancer Care CentreRecruiting
  • Peninsula & South Eastern Haematology and Oncology GroupRecruiting
  • Austin Health, Olivia Newton-John Cancer Research & Wellness CentreRecruiting
  • Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec KraloveRecruiting
  • Onkologicka klinika, Fakultni Nemocnice OlomoucRecruiting
  • ICORecruiting
  • CHU Bordeaux Hospital Saint-AndreRecruiting
  • Centre Jean PerrinRecruiting
  • Centre Oscar LambretRecruiting
  • Centre Léon BérardRecruiting
  • CHU NantesRecruiting
  • ICANSRecruiting
  • Istituto Europeo OncologicoRecruiting
  • Istituto Nazionale Tumori Fondazione G. PascaleRecruiting
  • Fondazione IRCCS Policlinico San MatteoRecruiting
  • Centro Ricerche Cliniche di Verona s.r.l.Recruiting
  • Ajou University HospitalRecruiting
  • Korea University HospitalRecruiting
  • Seoul National University HospitalRecruiting
  • Severance HospitalRecruiting
  • Sarawak General HospitalRecruiting
  • Med - Polonia Sp. z o. o.Recruiting
  • Narodowy Instytut OnkologiiRecruiting
  • Instytut MSF Sp zooRecruiting
  • National Cancer centre SingaporeRecruiting
  • NEXT Oncology IOB Hospital QuirónsaludRecruiting
  • Clinica Universidad de NavarraRecruiting
  • Hospital Universitario QuirónsaludRecruiting
  • Hospital Universitario Virgen del RocíoRecruiting
  • Hospital Universitario Miguel ServetRecruiting
  • E-DA hospitalRecruiting
  • Taipei Tzu Chi HospitalRecruiting
  • National Cheng Kung University HospitalRecruiting
  • National Taiwan University HospitalRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

RMC-6291

Arm Description

Dose Escalation and Dose Expansion

Outcomes

Primary Outcome Measures

Adverse events
Number of participants with adverse events
Dose Limiting Toxicities
Number of participants with dose limiting toxicities

Secondary Outcome Measures

Maximum Observed Blood Concentration of RMC-6291
Cmax
Time to Reach Maximum Blood Concentration of RMC-6291
Tmax
Area Under Blood Concentration Time Curve of RMC-6291
AUC
Elimination Half-Life of RMC-6291
t1/2
Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing
accumulation ratio
Overall Response Rate (ORR)
Overall response rate per RECIST v1.1
Duration of Response (DOR)
Duration of response per RECIST v1.1
Disease Control Rate (DCR)
Disease control rate per RECIST v1.1
Time to Response (TTR)
Time to response per RECIST v1.1
Progression-Free Survival (PFS)
Progression-free survival per RECIST v1.1

Full Information

First Posted
July 11, 2022
Last Updated
October 17, 2023
Sponsor
Revolution Medicines, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT05462717
Brief Title
Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
Official Title
Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
September 19, 2022 (Actual)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
December 2025 (Anticipated)

3. Sponsor/Collaborators

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

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 safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.
Detailed Description
This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma, Advanced Solid Tumor
Keywords
RMC-6291, RAS(ON), KRAS, KRASG12C, KRASG12C(ON), Targeted therapy, Metastatic cancer, Lung Cancer, Lung Neoplasms, Thoracic Neoplasms, Non-small Cell Lung Cancer, Carcinoma, Non-Small Cell Lung, NSCLC, Colorectal Cancer, Colonic Neoplasms, CRC, Appendiceal Cancer, KRAS mutation, STK11/LKB1, KEAP1, bronchial neoplasms, respiratory tract neoplasms, neoplasms by site, neoplasms, Colon Cancer, Rectal Cancer, lung disease, respiratory tract diseases, Pancreatic Cancer, Carcinoma, Pancreatic Ductal, PDAC, Gastrointestinal Neoplasms, Intestinal Neoplasms, Esophageal cancer, Ampullary cancer, Gastric Cancer, Gynecological Cancer, Ovarian Cancer, Endometrial Cancer

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
117 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
RMC-6291
Arm Type
Experimental
Arm Description
Dose Escalation and Dose Expansion
Intervention Type
Drug
Intervention Name(s)
RMC-6291
Intervention Description
Oral tablet once or twice a day
Primary Outcome Measure Information:
Title
Adverse events
Description
Number of participants with adverse events
Time Frame
up to 3 years
Title
Dose Limiting Toxicities
Description
Number of participants with dose limiting toxicities
Time Frame
The first 21 days (i.e. Cycle 1)
Secondary Outcome Measure Information:
Title
Maximum Observed Blood Concentration of RMC-6291
Description
Cmax
Time Frame
7 Cycles
Title
Time to Reach Maximum Blood Concentration of RMC-6291
Description
Tmax
Time Frame
7 Cycles
Title
Area Under Blood Concentration Time Curve of RMC-6291
Description
AUC
Time Frame
7 Cycles
Title
Elimination Half-Life of RMC-6291
Description
t1/2
Time Frame
7 Cycles
Title
Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing
Description
accumulation ratio
Time Frame
7 Cycles
Title
Overall Response Rate (ORR)
Description
Overall response rate per RECIST v1.1
Time Frame
3 years
Title
Duration of Response (DOR)
Description
Duration of response per RECIST v1.1
Time Frame
3 years
Title
Disease Control Rate (DCR)
Description
Disease control rate per RECIST v1.1
Time Frame
3 years
Title
Time to Response (TTR)
Description
Time to response per RECIST v1.1
Time Frame
3 years
Title
Progression-Free Survival (PFS)
Description
Progression-free survival per RECIST v1.1
Time Frame
3 years

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-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments. ECOG performance status 0 or 1 Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation Adequate organ function Exclusion Criteria: Primary central nervous system (CNS) tumors Active brain metastases Known impairment of GI function that would alter the absorption Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment. Prior therapy with KRASG12C (ON) inhibitor Other inclusion/exclusion criteria may apply.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Revolution Medicines, Inc.
Phone
(650) 779-2300
Email
CT-inquiries@RevMed.com
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
Highlands Oncology Group
City
Springdale
State/Province
Arkansas
ZIP/Postal Code
72762
Country
United States
Individual Site Status
Recruiting
Facility Name
UC Irvine Cancer Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Recruiting
Facility Name
UC Davis Cancer Center
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Individual Site Status
Recruiting
Facility Name
UCSF
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Individual Site Status
Recruiting
Facility Name
University of Miami School of Medicine Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Recruiting
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Recruiting
Facility Name
American Oncology Partners of Maryland
City
Bethesda
State/Province
Maryland
ZIP/Postal Code
20817
Country
United States
Individual Site Status
Recruiting
Facility Name
Dana-Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Name
Roswell Park Comprehensive Cancer Center
City
Buffalo
State/Province
New York
ZIP/Postal Code
14203
Country
United States
Individual Site Status
Recruiting
Facility Name
MSK Cancer Center
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Individual Site Status
Recruiting
Facility Name
Columbia University Irving Medical Center
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Individual Site Status
Recruiting
Facility Name
Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Name
Next Oncology
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
START
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78229
Country
United States
Individual Site Status
Recruiting
Facility Name
Next Oncology Virginia
City
Fairfax
State/Province
Virginia
ZIP/Postal Code
22031
Country
United States
Individual Site Status
Recruiting
Facility Name
Southside Cancer Care Centre
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2228
Country
Australia
Individual Site Status
Recruiting
Facility Name
Peninsula & South Eastern Haematology and Oncology Group
City
Frankston
State/Province
Victoria
ZIP/Postal Code
3199
Country
Australia
Individual Site Status
Recruiting
Facility Name
Austin Health, Olivia Newton-John Cancer Research & Wellness Centre
City
Heidelberg
State/Province
Victoria
ZIP/Postal Code
3084
Country
Australia
Individual Site Status
Recruiting
Facility Name
Klinika onkologie a radioterapie, Fakultni Nemocnice Hradec Kralove
City
Hradec Králové
ZIP/Postal Code
50005
Country
Czechia
Individual Site Status
Recruiting
Facility Name
Onkologicka klinika, Fakultni Nemocnice Olomouc
City
Olomouc
ZIP/Postal Code
77900
Country
Czechia
Individual Site Status
Recruiting
Facility Name
ICO
City
Angers
ZIP/Postal Code
49055
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Bordeaux Hospital Saint-Andre
City
Bordeaux
ZIP/Postal Code
33000
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Jean Perrin
City
Clermont-Ferrand
ZIP/Postal Code
63011
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Oscar Lambret
City
Lille
ZIP/Postal Code
59000
Country
France
Individual Site Status
Recruiting
Facility Name
Centre Léon Bérard
City
Lyon
ZIP/Postal Code
69008
Country
France
Individual Site Status
Recruiting
Facility Name
CHU Nantes
City
Nantes
ZIP/Postal Code
44093
Country
France
Individual Site Status
Recruiting
Facility Name
ICANS
City
Strasbourg
ZIP/Postal Code
67200
Country
France
Individual Site Status
Recruiting
Facility Name
Istituto Europeo Oncologico
City
Milano
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Recruiting
Facility Name
Istituto Nazionale Tumori Fondazione G. Pascale
City
Napoli
ZIP/Postal Code
80131
Country
Italy
Individual Site Status
Recruiting
Facility Name
Fondazione IRCCS Policlinico San Matteo
City
Pavia
ZIP/Postal Code
27100
Country
Italy
Individual Site Status
Recruiting
Facility Name
Centro Ricerche Cliniche di Verona s.r.l.
City
Verona
ZIP/Postal Code
37134
Country
Italy
Individual Site Status
Recruiting
Facility Name
Ajou University Hospital
City
Suwon-si
State/Province
Gyeonggi-do
ZIP/Postal Code
16499
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Korea University Hospital
City
Seoul
ZIP/Postal Code
02708
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Seoul National University Hospital
City
Seoul
ZIP/Postal Code
3080
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Severance Hospital
City
Seoul
ZIP/Postal Code
3722
Country
Korea, Republic of
Individual Site Status
Recruiting
Facility Name
Sarawak General Hospital
City
Kuching
ZIP/Postal Code
93586
Country
Malaysia
Individual Site Status
Recruiting
Facility Name
Med - Polonia Sp. z o. o.
City
Poznań
ZIP/Postal Code
60-693
Country
Poland
Individual Site Status
Recruiting
Facility Name
Narodowy Instytut Onkologii
City
Warsaw
ZIP/Postal Code
02-781
Country
Poland
Individual Site Status
Recruiting
Facility Name
Instytut MSF Sp zoo
City
Łódź
ZIP/Postal Code
90-302
Country
Poland
Individual Site Status
Recruiting
Facility Name
National Cancer centre Singapore
City
Singapore
ZIP/Postal Code
168583
Country
Singapore
Individual Site Status
Recruiting
Facility Name
NEXT Oncology IOB Hospital Quirónsalud
City
Barcelona
ZIP/Postal Code
08023
Country
Spain
Individual Site Status
Recruiting
Facility Name
Clinica Universidad de Navarra
City
Pamplona
ZIP/Postal Code
31008
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Quirónsalud
City
Pozuelo De Alarcón
ZIP/Postal Code
28223
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Virgen del Rocío
City
Sevilla
ZIP/Postal Code
41013
Country
Spain
Individual Site Status
Recruiting
Facility Name
Hospital Universitario Miguel Servet
City
Zaragoza
ZIP/Postal Code
50009
Country
Spain
Individual Site Status
Recruiting
Facility Name
E-DA hospital
City
Kaohsiung
State/Province
Yanchao District
ZIP/Postal Code
82445
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
Taipei Tzu Chi Hospital
City
New Taipei City
ZIP/Postal Code
231
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
National Cheng Kung University Hospital
City
Tainan
ZIP/Postal Code
70457
Country
Taiwan
Individual Site Status
Recruiting
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10048
Country
Taiwan
Individual Site Status
Recruiting

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

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