Clinical trial • Phase III • Oncology|Rare Disease

(12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE for Resected pancreatic ductal adenocarcinoma (PDAC)

Phase III trial of (12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,…

Overview

Trial Therapeutic Area
Oncology|Rare Disease
Trial Disease
Resected pancreatic ductal adenocarcinoma (PDAC)
Trial Stage
Phase III
Drug Modality
Small molecule

Key dates

Initial CTIS Submission Date
14-01-2026
First CTIS Authorization Date
27-04-2026

Trial design

Randomised, open-label, arm a: daraxonrasib (rmc-6236) oral tablet (investigational product daraxonrasib (rmc-6236); product record lists route oral use and a max daily dose amount of 300 mg). arm b: observation (standard of care observation).-controlled Phase III trial in France, Germany, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Arm A: Daraxonrasib (RMC-6236) oral tablet (investigational product DARAXONRASIB (RMC-6236); product record lists route ORAL USE and a max daily dose amount of 300 mg). Arm B: Observation (standard of care observation).
Target Sample Size
402
Trial Duration For Participant
730

Eligibility

Recruits 402 Vulnerable population selected. Participants must be at least 18 years old and provide informed consent (principal inclusion criterion: "At least 18 years old and has provided informed consent."). Country-specific informed consent forms and subject information sheets are listed among submitted documents..

Vulnerable Population
Vulnerable population selected. Participants must be at least 18 years old and provide informed consent (principal inclusion criterion: "At least 18 years old and has provided informed consent."). Country-specific informed consent forms and subject information sheets are listed among submitted documents.

Inclusion criteria

  • {"criterion_text":"- At least 18 years old and has provided informed consent.\n- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.\n- Histologically confirmed PDAC with successful (R0/R1) curative intent surgical resection and no evidence of recurrent or metastatic disease.\n- Must have received perioperative (neoadjuvant, adjuvant, or a combination of both) multi-agent chemotherapy.\n- Must have completed most recent treatment within the past 12 weeks.\n- Adequate organ function (bone marrow, liver, kidney, coagulation).\n- Documented RAS mutation status.\n- Able to take oral medications."}

Exclusion criteria

  • {"criterion_text":"- Prior therapy with direct RAS-targeted therapy (eg. degraders and/or inhibitors).\n- Any conditions that may affect the ability to take or absorb study drug.\n- Major surgery within 28 days prior to randomization.\n- Patient is unable or unwilling to comply with protocol-required study visits or procedures."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- Disease-Free Survival (DFS) per Investigator DFS defined as the time from randomization until disease recurrence or death from any cause, whichever occurs first. Recurrence is per response evaluation criteria in solid tumors (RECIST) v1.1 as assessed by Investigator.","definition_or_measurement_approach":"DFS defined as the time from randomization until disease recurrence or death from any cause, whichever occurs first. Recurrence per RECIST v1.1 as assessed by Investigator."}

Secondary endpoints

  • {"endpoint_text":"- Overall survival (OS) - OS is defined as the time from randomization until death from any cause","definition_or_measurement_approach":"OS defined as the time from randomization until death from any cause."}
  • {"endpoint_text":"- DFS per blinded independent central review (BICR) - DFS defined as the time from randomization until disease recurrence or death from any cause, whichever occurs first. Recurrence is per RECIST v1.1 as assessed by BICR","definition_or_measurement_approach":"DFS per BICR defined as time from randomization until disease recurrence or death, recurrence per RECIST v1.1 assessed by blinded independent central review."}
  • {"endpoint_text":"- DFS Rate at 1 year and 2 years - DFS rate defined as percentage of patients who are disease free at 1 year and 2 years, respectively","definition_or_measurement_approach":"DFS rate defined as percentage of patients who are disease free at 1 year and 2 years."}
  • {"endpoint_text":"- OS rate at 1 year and 2 years - OS rate defined as percentage of patients who are alive at 1 year and 2 years, respectively.","definition_or_measurement_approach":"OS rate defined as percentage of patients alive at 1 year and 2 years."}
  • {"endpoint_text":"- Safety and tolerability of daraxonrasib - Incidence of adverse events (AEs) and changes from baseline in vital signs, ECOG performance score, and clinical laboratory tests","definition_or_measurement_approach":"Safety and tolerability measured by incidence of adverse events and changes from baseline in vital signs, ECOG performance status, and clinical laboratory tests."}
  • {"endpoint_text":"- Pharmacokinetics (PK) - Predose concentration of daraxonrasib","definition_or_measurement_approach":"PK endpoint: predose concentration of daraxonrasib."}

Recruitment

Digital Remote Recruitment
Yes
Planned Sample Size
402
Recruitment Window Months
49
Consent Approach
Informed consent is required from each participant (principal inclusion: "At least 18 years old and has provided informed consent."). Country-specific subject information sheets and informed consent forms were submitted (documents include ICFs and SIS in country versions). Submitted materials include ICF / SIS documents in multiple country-language versions (French, German, Italian, Spanish) and lay protocol synopses (including English).

Methods

  • Patient Poster (site poster) — country-specific versions submitted (e.g., France V01 FRAfr, Germany V01DEU, Italy V01ITA, Spain V01ESP).
  • Digital Patient Brochure / Study Participant Information (digital) — digital recruitment materials present (country-specific).
  • Pre-Enrollment / Pre-Enrollment Card / Pre Enrollment Information Card — materials for pre-enrolment available (country-specific).
  • Physician Referral Letter and Physician Referral Brochure — materials targeting healthcare professionals to refer patients.
  • Site Poster — materials for display at participating sites.
  • Patient Brochure — printed/handout brochures for patients (country-specific).
  • Chart Review Checklist and Eligibility Criteria Cards — tools for site staff to identify potential participants via record review.
  • Recruitment and Informed Consent Procedure (K1) / Patient Recruitment procedure — documented site recruitment procedures and ICF / subject information sheets submitted.

Geography

Total Number Of Sites
26
Total Number Of Participants
98

France

Earliest CTIS Part Ii Submission Date
23-01-2026
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
95
Number Of Sites
6
Number Of Participants
26

Sites

Site Name
Hospital Edouard Herriot
Department Name
Medical Oncology
Contact Person Name
Alice DURAND
Contact Person Email
alice.durand@chu-lyon.fr
Site Name
Hopital Paul Brousse
Department Name
Medical Oncology
Contact Person Name
Pascal HAMMEL
Contact Person Email
pascal.hammel@aphp.fr
Site Name
Centre Hospitalier Universitaire De Lille
Department Name
Medical Oncology
Contact Person Name
Anthony TURPIN
Contact Person Email
anthony.turpin@chu-lille.fr
Site Name
Centre De Lutte Contre Le Cancer Eugene Marquis
Department Name
Medical Oncology
Contact Person Name
Julien EDELINE
Contact Person Email
j.edeline@rennes.unicancer.fr
Site Name
Institut Paoli Calmettes
Department Name
Medical Oncology
Contact Person Name
Emmanuel MITRY
Contact Person Email
mitryje@ipc.unicancer.fr
Site Name
Institut Gustave Roussy
Department Name
Gastroenterology
Contact Person Name
Michel DUCREUX

Germany

Earliest CTIS Part Ii Submission Date
02-04-2026
Latest Decision Or Authorization Date
27-04-2026
Processing Time Days
25
Number Of Sites
6
Number Of Participants
24

Sites

Site Name
Krankenhaus Nordwest GmbH
Department Name
Institute of Clinical Cancer Research (IKF)
Contact Person Name
Thomas Götze
Contact Person Email
Goetze.thorsten@khnw.de
Site Name
LMU Klinikum Muenchen AöR
Department Name
Medizinische Klinik und Poliklinik III
Contact Person Name
Sabrina Opatz
Site Name
Universitaetsklinikum Schleswig-Holstein AöR
Department Name
Medizinische Klinik 1
Contact Person Name
Jens Marquardt
Contact Person Email
jens.marquardt@uksh.de
Site Name
Sana Kliniken Berlin-Brandenburg GmbH
Department Name
Clinic for Internal Medicine IV: Hematology, Oncology and Palliative Medicine
Contact Person Name
Uwe Pelzer
Contact Person Email
uwe.pelzer@sana.de
Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
Nationales Centrum für Tumorerkrankungen (NCT), Medizinische Onkologie
Contact Person Name
Christoph Springfeld
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Klinik für Innere Medizin I
Contact Person Name
Thomas Seufferlein

Italy

Earliest CTIS Part Ii Submission Date
23-01-2026
Latest Decision Or Authorization Date
28-04-2026
Processing Time Days
95
Number Of Sites
7
Number Of Participants
24

Sites

Site Name
Fondazione Policlinico Universitario Agostino Gemelli IRCCS
Department Name
UOC Oncologia Medica
Contact Person Name
Giampaolo Tortora
Site Name
Azienda Ospedaliero Universitaria Pisana
Department Name
UO Oncologia Medica 2
Contact Person Name
Chiara Cremolini
Contact Person Email
chiaracremolini@gmail.com
Site Name
Azienda Ospediera Universitaria Universita' Degli Studi Della Campania Luigi Vanvitelli
Department Name
UOC Oncoematologia
Contact Person Name
Ferdinando De Vita
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Medical Oncology
Contact Person Name
Monica Niger
Site Name
Istituto Oncologico Veneto
Department Name
UOC Oncologia 1
Contact Person Name
Sara Lonardi
Contact Person Email
sara.lonardi@iov.veneto.it
Site Name
Centro Ricerche Cliniche Di Verona S.r.l.
Department Name
Digestive Molecular Clinical Oncology Research Unit
Contact Person Name
Davide Melisi
Contact Person Email
davide.melisi@univr.it
Site Name
Istituto Europeo Di Oncologia S.r.l.
Department Name
Division of Gastrointestinal and Neuroendocrine tumors
Contact Person Name
Lorenzo Gervaso
Contact Person Email
lorenzo.gervaso@ieo.it

Spain

Earliest CTIS Part Ii Submission Date
21-04-2026
Latest Decision Or Authorization Date
04-05-2026
Processing Time Days
13
Number Of Sites
7
Number Of Participants
24

Sites

Site Name
University Hospital Virgen Del Rocio S.L.
Department Name
Oncology
Contact Person Name
Inmaculada Gallego Jimenez
Contact Person Email
inmagaji@gmail.com
Site Name
Hospital Universitario Miguel Servet
Department Name
Oncology
Contact Person Name
Roberto Pazo Cid
Contact Person Email
rpazo@salud.aragon.es
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Contact Person Name
Jaume Capdevila Castillo
Contact Person Email
jcapdevila@vhio.net
Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncology
Contact Person Name
María del Sol Huerta Alvaro
Contact Person Email
mhuerta@incliva.es
Site Name
Clinica Universidad De Navarra
Department Name
Oncology
Contact Person Name
Mariano Ponz Sarvise
Contact Person Email
mponz@unav.es
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Rocio Garcia Carbonero
Contact Person Email
rgcarbonero@gmail.com
Site Name
Hospital Clinic De Barcelona
Department Name
Oncology
Contact Person Name
Teresa Macarulla Mercade
Contact Person Email
macarulla@clinic.cat

Sponsor

Primary sponsor

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

Contract research organisations

Name
Everest Clinical Research Corporation
Responsibilities
Independent Data Monitoring Committee (IDMC)
Name
IQVIA Limited
Responsibilities
Multiple operational and clinical trial services (codes listed in record)
Name
Endpoint Clinical Inc.
Responsibilities
Integration services, Randomization List services, UAT Plan services
Name
Perceptive Informatics Inc.
Responsibilities
Central imaging reader and services
Name
Primevigilance USA Inc.
Responsibilities
Hosting the global safety database for the IMP

Third parties

  • {"country":"Canada","full_name":"Everest Clinical Research Corporation","duties_or_roles":"Independent Data Monitoring Committee (IDMC)","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"Target SDV","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Iqvia Laboratories Limited","duties_or_roles":"Sample storage","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Cisys Inc.","duties_or_roles":"system for sites to upload documents for the eligibility review and approve/ot approve patients to enrol to the study.","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central imaging reader and services","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"Multiple operational responsibilities (codes listed in record) including clinical trial services and data management (specific duties provided by sponsorDuties codes).","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Endpoint Clinical Inc.","duties_or_roles":"Integration services, Randomization List services, UAT Plan services","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"PK analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"Biomarker laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"eCOA/Questionnaires administration and eDiaries","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"Hosting the global safety database for the IMP","organisation_type":"Pharmaceutical company"}

Investigational products

Investigational Product Name
DARAXONRASIB (RMC-6236)
Active Substance
(12M)-(1S,2S)-N-((63S,4S,Z)-11-ETHYL-12-(2-((S)-1-METHOXYETHYL)-5-(4-METHYLPIPERAZIN-1-YL)PYRIDIN-3-YL)-10,10-DIMETHYL-5,7-DIOXO-61,62,63,64,65,66-HEXAHYDRO-11H-8-OXA-2(4,2)-THIAZOLA-1(5,3)-INDOLA-6(1,3)-PYRIDAZINACYCLOUNDECAPHANE-4-YL)-2-METHYLCYCLOPROPANE-1-CARBOXAMIDE
Modality
Small molecule
Routes Of Administration
ORAL USE
Route
Oral
Authorisation Status
Investigational
Maximum Dose
300 mg per day (max daily dose listed)

Related trials

Other published trials that may interest you.