Clinical trial • Phase I/II • Oncology|Respiratory

RMC-6291 for Non-small cell lung cancer|RAS G12C-mutated non-small cell lung cancer

Phase I/II trial of RMC-6291 for Non-small cell lung cancer|RAS G12C-mutated non-small cell lung cancer.

Overview

Trial Therapeutic Area
Oncology|Respiratory
Trial Disease
Non-small cell lung cancer|RAS G12C-mutated non-small cell lung cancer
Trial Stage
Phase I/II
Drug Modality
Small molecule|Monoclonal antibody

Key dates

Initial CTIS Submission Date
29-02-2024
First CTIS Authorization Date
17-06-2024

Trial design

open-label, none/not specified-controlled, adaptive Phase I/II trial across 41 sites in Germany, Netherlands, Spain and others.

Open Label
Yes
Comparator
None/Not specified
Adaptive
True, includes dose-escalation and dose-expansion elements and safety lead-in cohorts (e.g. Part 1 and Part 2 cohorts A2, A3, A4) to define RP2DS; adaptation driven by safety/DLT assessments and PK/safety data.
Biomarker Stratified
True, biomarker: RAS G12C mutation
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
105

Eligibility

Recruits 105 Vulnerable population selected. Participants must be ≥ 18 and must sign the Informed Consent Form (ICF). Country-/site-specific informed consent documents are provided (Main ICF, Pregnancy ICF, Optional Biopsy ICF, Scout ICF, Future Research ICF) as listed in the application documents..

Vulnerable Population
Vulnerable population selected. Participants must be ≥ 18 and must sign the Informed Consent Form (ICF). Country-/site-specific informed consent documents are provided (Main ICF, Pregnancy ICF, Optional Biopsy ICF, Scout ICF, Future Research ICF) as listed in the application documents.

Inclusion criteria

  • {"criterion_text":"- 1. ≥ 18 years of age and signed the Informed Consent Form (ICF)"}
  • {"criterion_text":"- 2. Patients that have solid tumor with RAS-G12C."}
  • {"criterion_text":"- 3. Patients that have received prior cancer treatment or are not able to tolerate regular treatments."}
  • {"criterion_text":"- 4. Patients that have at least one tumor lesion (an area of abnormal tissue) that can be measured."}
  • {"criterion_text":"- 5. Patients that have adequate organ function (bone marrow, liver, kidney)."}

Exclusion criteria

  • {"criterion_text":"- 1. Participants that have primary brain and spinal cord tumor."}
  • {"criterion_text":"- 2. Participants thathave gastrointestinal problems that may affect absorption of RMC-6291."}
  • {"criterion_text":"- 3. Participants thathad any major surgery in the last 4 weeks."}
  • {"criterion_text":"- 4. Participants thathave any other medical condition that may interfere with the study drugs."}
  • {"criterion_text":"- 5. Participants that have previously taken targeted therapy for KRAS mutation."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Incidence of DLTs (Part 1 and Part 2 Cohort A2, A3 and A4 safety lead-in only)","definition_or_measurement_approach":"DLTs assessed during the specified safety lead-in periods (Part 1 and Part 2 cohorts A2, A3 and A4) as reported in the protocol safety assessments."}
  • {"endpoint_text":"- Incidence of TEAEs, TRAEs, SAEs, and clinically significant changes in laboratory test values, ECGs, and vital signs","definition_or_measurement_approach":"Adverse events and clinically significant changes monitored and recorded (TEAEs, TRAEs, SAEs) and changes in laboratory tests, ECGs and vital signs per protocol safety assessments."}

Secondary endpoints

  • {"endpoint_text":"- RMC-6291 plasma concentrations overtime and PK parameters as applicable.","definition_or_measurement_approach":"Plasma concentration-time profiling and calculation of PK parameters for RMC-6291."}
  • {"endpoint_text":"- RMC-6291 plasma and RMC-6236 blood concentration over time and PK parameters as applicable","definition_or_measurement_approach":"Plasma (RMC-6291) and blood (RMC-6236) concentration-time profiling and PK parameter calculations as applicable."}
  • {"endpoint_text":"- • ORR and DOR per RECIST v1.1","definition_or_measurement_approach":"Objective response rate (ORR) and duration of response (DOR) assessed per RECIST v1.1 criteria."}

Recruitment

Planned Sample Size
105
Recruitment Window Months
34
Consent Approach
Participants (≥18 years) must provide written informed consent (sign the ICF). Country- and language-specific ICFs are provided (Main ICF and additional forms such as Pregnancy ICF, Optional Biopsy ICF, Scout ICF, Future Research ICF) as per the submitted documents (versions available for DE, NL, ES, IT, FR, etc.).

Geography

Total Number Of Sites
41
Total Number Of Participants
162

Germany

Earliest CTIS Part Ii Submission Date
08-05-2024
Latest Decision Or Authorization Date
16-12-2025
Processing Time Days
587
Number Of Sites
7
Number Of Participants
24

Sites

Site Name
Technische Universitaet Dresden
Department Name
Medizinische Klinik und Poliklinik I
Contact Person Name
Martin Wermke
Site Name
Goethe University Frankfurt
Department Name
Medizinische Klinik II
Contact Person Name
Martin Sebastian
Contact Person Email
sebastian@med.uni-frankfurt.de
Site Name
University Hospital Cologne AöR
Department Name
Klinik I für Innere Medizin
Contact Person Name
Jürgen Wolf
Contact Person Email
juergen.wolf@uk-koeln.de
Site Name
Lungenfachklinik Immenhausen
Contact Person Name
Achim Rittmeyer
Site Name
Thoraxklinik Heidelberg gGmbH
Department Name
Universitätsklinikum Heidelberg
Contact Person Name
Farastuk Bozorgmehr
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Medizinische Klinik mit Schwerpunkt Onkologie, Hämatologie und Tumorimmunologie
Contact Person Name
Damian Rieke
Contact Person Email
damian.rieke@charite.de
Site Name
Stiftung Krankenhaus Bethanien Fuer Die Grafschaft Moers
Department Name
Klinik für Lungen- & Bronchialheilkunde
Contact Person Name
Kato Kambartel
Contact Person Email
kambartel@bethanienmoers.de

Netherlands

Earliest CTIS Part Ii Submission Date
22-05-2024
Latest Decision Or Authorization Date
11-12-2025
Processing Time Days
568
Number Of Sites
4
Number Of Participants
24

Sites

Site Name
Het Nederlands Kanker Instituut-Antoni van Leeuwenhoek Ziekenhuis Stichting
Department Name
Clinical Research Unit
Contact Person Name
Gerrina Ruiter
Contact Person Email
cpm-cru@nki.nl
Site Name
Universitair Medisch Centrum Utrecht
Department Name
Medical Oncology
Contact Person Name
Hilde Nienhuis
Contact Person Email
oncostudies@umcutrecht.nl
Site Name
Universitair Medisch Centrum Groningen
Department Name
Department of pulmonology and tuberculosis
Contact Person Name
Anthonie J. van der Wekken
Contact Person Email
a.j.van.der.wekken@umcg.nl
Site Name
Leids Universitair Medisch Centrum (LUMC)
Department Name
Department of Pulmonary Diseases
Contact Person Name
Egbert F. Smit
Contact Person Email
e.f.smit@lumc.nl

Spain

Earliest CTIS Part Ii Submission Date
17-05-2024
Latest Decision Or Authorization Date
15-12-2025
Processing Time Days
577
Number Of Sites
13
Number Of Participants
24

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Oncologia
Contact Person Name
Alejandro Falcon
Contact Person Email
afalconglez@gmail.com
Site Name
Hospital Clinico San Carlos
Department Name
Oncologia
Contact Person Name
Jorge Bartolome
Site Name
Clinica Universidad De Navarra
Department Name
Oncologia
Contact Person Name
Miguel Fernandez De Sanmamed
Contact Person Email
msanmamed@unav.es
Site Name
Institut Catala D'oncologia
Department Name
Oncologia
Contact Person Name
Marta Domenech Viñolas
Contact Person Email
mdomenech@iconcologia.net
Site Name
Complexo Hospitalario Universitario A Coruna
Department Name
Oncologia Medica
Contact Person Name
Maria Rosario Garcia Campelo
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncologia
Contact Person Name
Luis Paz-Ares Rodriguez
Contact Person Email
luis.paz-ares@salud.madrid.org
Site Name
Hospital Universitario Y Politecnico La Fe
Department Name
Oncologia
Contact Person Name
Oscar Juan Vidal
Contact Person Email
juan_osc@gva.es
Site Name
Clinica Universidad De Navarra (second site entry)
Department Name
Oncologia
Contact Person Name
Miguel Fernandez De Sanmamed
Contact Person Email
msanmamed@unav.es
Site Name
Fundacion Instituto Valenciano De Oncologia
Department Name
Oncologia
Contact Person Name
David Lorente Estelles
Contact Person Email
dlorente@fivo.org
Site Name
Hospital Universitario Regional De Malaga
Department Name
Oncologia Medica
Contact Person Name
Vanesa Gutierrez
Contact Person Email
VanesaGutierrez@gmail.com
Site Name
Hospital Universitario Ramon Y Cajal
Department Name
Oncologia
Contact Person Name
Pilar Garrido
Contact Person Email
pgarrido@salud.madrid.org
Site Name
Hospital Universitario Fundacion Jimenez Diaz
Department Name
Oncologia
Contact Person Name
Bernard Doger de Speville Uribe
Contact Person Email
bernard.doger@startmadrid.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncologia
Contact Person Name
Patricia Iranzo
Contact Person Email
piranzo@vhio.net

Italy

Earliest CTIS Part Ii Submission Date
20-05-2024
Latest Decision Or Authorization Date
17-12-2025
Processing Time Days
576
Number Of Sites
7
Number Of Participants
24

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
Unità Operativa Complessa Fase 1
Contact Person Name
Gennaro Daniele
Site Name
Istituto Romagnolo Per Lo Studio Dei Tumori Dino Amadori IRST S.r.l.
Department Name
Oncologia Medica
Contact Person Name
Angelo Delmonte
Contact Person Email
angelo.delmonte@irst.emr.it
Site Name
ASST Grande Ospedale Metropolitano Niguarda
Department Name
SC Oncologia Falck
Contact Person Name
Salvatore Siena
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Medical Oncology and Hematology
Contact Person Name
Sara Cresta
Site Name
I.F.O. Istituti Fisioterapici Ospitalieri
Department Name
UOSD Clinical Trial Unit Phase 1and Precision Medicine
Contact Person Name
Lorenza Landi
Contact Person Email
lorenza.landi@ifo.it
Site Name
Azienda Unita Sanitaria Locale Della Romagna
Department Name
Unità Clinica Fase 1 – UO Oncologia di Ravenna
Contact Person Name
Manlo D’Arcangelo
Site Name
Azienda Ospedaliero-Universitaria San Luigi Gonzaga
Department Name
SSD Oncologia polmonare-A.O.U. San Luigi Gonzaga - Orbassano
Contact Person Name
Silvia Novello
Contact Person Email
silvia.novello@unito.it

France

Earliest CTIS Part Ii Submission Date
25-04-2024
Latest Decision Or Authorization Date
11-12-2025
Processing Time Days
595
Number Of Sites
10
Number Of Participants
66

Sites

Site Name
Centre Francois Baclesse
Contact Person Name
Hubert CURCIO
Contact Person Email
h.curcio@baclesse.unicancer.fr
Site Name
Institut Bergonie
Contact Person Name
Sophie COUSIN
Contact Person Email
s.cousin@bordeaux-unicancer.fr
Site Name
Institut Gustave Roussy
Contact Person Name
Anas Gazzah
Contact Person Email
anas.gazzah@gustaveroussy.fr
Site Name
Institut Curie
Contact Person Name
Pauline DU RUSQUEC
Contact Person Email
Pauline.durusquec@curie.fr
Site Name
Hospices Civils De Lyon
Contact Person Name
Michael DURUISSEAUX
Site Name
Hospital Foch
Contact Person Name
Jaafar BENNOUNA
Contact Person Email
j.bennouna@hopital-foch.com
Site Name
Oncopole Claudius Regaud
Contact Person Name
Audrey RABEAU
Contact Person Email
Rabeau.audrey@iuct-oncopole.fr
Site Name
Centr Georges Francois Leclerc
Contact Person Name
François GHIRINGHELLI
Contact Person Email
fghiringhelli@cgfl.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Department Name
Oncologie Medicale, Unité d'Oncologie Thoracique
Contact Person Name
Elvire PONS-TOSTIVINT
Contact Person Email
elvire.pons@chu-nantes.fr
Site Name
Centre Hospitalier Universitaire De Lille
Contact Person Name
Alexis CORTOT
Contact Person Email
Alexis.cortot@chru-lille.fr

Sponsor

Primary sponsor

Full Name
Revolution Medicines Inc.
Organisation Type
Pharmaceutical company
Country Of Registered Address
United States

Contract research organisations

Name
PPD Development LP
Responsibilities
Contract Research Organization, Clinical Database Management, Pharmacovigilance services.
Name
PPD International Holdings LLC
Responsibilities
4

Third parties

  • {"country":"United States","full_name":"Atreo Inc.","duties_or_roles":"3","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ctDNA Analysis","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"Patient travel & Reimbursement","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Myonex LLC","duties_or_roles":"Clinical Supply","organisation_type":"Hospital/Clinic/Other health care facility"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Sherpa Clinical Packaging LLC","duties_or_roles":"Collect and read ECG scans","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Propharma Group LLC","duties_or_roles":"9","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"8","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Edetek Inc.","duties_or_roles":"Stats Programing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"4","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Electronic drug diaries","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"PPD Development LP","duties_or_roles":"Contract Research Organization, Clinical Database Management, Pharmacovigilance services.","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Aperio Clinical Outcomes LLC","duties_or_roles":"6","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Biotel Research LLC","duties_or_roles":"Collect and read ECG scans","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD International Holdings LLC","duties_or_roles":"4","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
RMC-6291
Active Substance
RMC-6291
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Maximum Dose
400 mg
Investigational Product Name
RMC-6236
Active Substance
(12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-...)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Maximum Dose
200 mg
Investigational Product Name
KEYTRUDA (Pembrolizumab)
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
SOLUTION FOR INFUSION
Route
SOLUTION FOR INFUSION
Authorisation Status
2
Maximum Dose
9.52 mg
Investigational Product Name
Pemetrexed STADA (Pemetrexed)
Active Substance
PEMETREXED
Modality
Small molecule
Routes Of Administration
CONCENTRATE FOR SOLUTION FOR INFUSION
Route
CONCENTRATE FOR SOLUTION FOR INFUSION
Authorisation Status
2
Maximum Dose
166.6 mg/m2
Investigational Product Name
Cisplatin (various MA holders)
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
SOLUTION FOR INFUSION
Authorisation Status
2
Maximum Dose
25 mg
Investigational Product Name
Carboplatin (various MA holders)
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
SOLUTION FOR INFUSION
Authorisation Status
2
Maximum Dose
35.71 mg
Combination Treatment
Yes

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