Clinical trial • Phase III • Oncology

(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 Metastatic pancreatic ductal adenocarcinoma

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
Trial Disease
Metastatic pancreatic ductal adenocarcinoma
Trial Stage
Phase III
Drug Modality
Small molecule
Orphan Drug
Yes

Key dates

Initial CTIS Submission Date
13-09-2024
First CTIS Authorization Date
13-12-2024

Trial design

Randomised, open-label, investigator’s choice of standard of care therapy (comparator agents listed include: irinotecan / irinotecan, irinotecan hydrochloride, fluorouracil (5-fu), folinic acid, paclitaxel albumin-bound, gemcitabine hydrochloride, oxaliplatin). dose and schedule not specified in the available record.-controlled Phase III trial across 16 sites in France, Spain, Italy and others.

Randomised
Yes
Open Label
Yes
Comparator
Investigator’s choice of standard of care therapy (comparator agents listed include: IRINOTECAN / irinotecan, IRINOTECAN HYDROCHLORIDE, FLUOROURACIL (5-FU), FOLINIC ACID, PACLITAXEL ALBUMIN-BOUND, GEMCITABINE HYDROCHLORIDE, OXALIPLATIN). Dose and schedule not specified in the available record.
Target Sample Size
324
Trial Duration For Participant
1035

Eligibility

Recruits 324 Vulnerable population flag is selected. Inclusion criterion 1 requires participants to be at least 18 years of age and to have provided informed consent and notes local regulatory requirements if the legal age of consent for study participation is >18 years. No further details on assent or specific vulnerable-population consent handling are provided in the record..

Vulnerable Population
Vulnerable population flag is selected. Inclusion criterion 1 requires participants to be at least 18 years of age and to have provided informed consent and notes local regulatory requirements if the legal age of consent for study participation is >18 years. No further details on assent or specific vulnerable-population consent handling are provided in the record.

Inclusion criteria

  • {"criterion_text":"- At least 18 years of age and has provided informed consent. Follow local regulatory requirements if the legal age of consent for study participation is >18 years old.\n- ECOG performance status 0 or 1.\n- Histologically or cytologically confirmed PDAC with metastatic disease\n- Measurable disease per RECIST 1.1\n- Adequate organ function (bone marrow, liver, kidney, coagulation)\n- One prior line of systemic therapy in the metastatic setting.\n- Documented RAS mutation status, either mutant or wild-type. RAS mutations are defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61).\n- Able to take oral medications"}

Exclusion criteria

  • {"criterion_text":"- Prior therapy with any direct RAS-targeted therapy (eg, degraders and/or inhibitors).\n- History of or known central nervous system metastatic disease.\n- Any conditions that may affect the ability to take or absorb study treatment.\n- Major surgery within 4 weeks prior to randomization.\n- Patient is unable or unwilling to comply with all protocol-required study visits or procedures."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- PFS is defined as the time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 and as assessed by BICR. OS is defined as the time from randomization until death from any cause.","definition_or_measurement_approach":"PFS: time from randomization until disease progression or death (whichever occurs first); progression assessed per RECIST v1.1 by blinded independent central review (BICR). OS: time from randomization until death from any cause."}

Recruitment

Planned Sample Size
324
Recruitment Window Months
34
Consent Approach
Informed consent must be provided by each participant; inclusion criterion 1 states: 'At least 18 years of age and has provided informed consent. Follow local regulatory requirements if the legal age of consent for study participation is >18 years old.' Multiple subject information and informed consent form documents in different languages (English, French, Spanish, Italian, German) are included in the submission, indicating consent materials are provided in those languages. No additional detailed description of remote consent, assent, or other consent procedures is provided in the record.

Geography

Total Number Of Sites
16
Total Number Of Participants
136

France

Earliest CTIS Part Ii Submission Date
25-10-2024
Latest Decision Or Authorization Date
08-12-2025
Processing Time Days
409
Number Of Sites
4
Number Of Participants
32

Sites

Site Name
Institut Gustave Roussy
Department Name
Pathologies Digestives
Contact Person Name
Michel Ducreux
Site Name
Institut Paoli Calmettes
Department Name
service d'oncologie medicale
Contact Person Name
Jean-Emmanuel Mitry
Contact Person Email
mitryje@ipc.uncancer.fr
Site Name
Hopital Paul Brousse
Department Name
Service oncologie digestive et medicale
Contact Person Name
Pascal Hammel
Contact Person Email
pascal.hammel@aphp.fr
Site Name
Centre De Lutte Contre Le Cancer Eugene Marquis
Department Name
Service d'Oncologie médicale
Contact Person Name
Julien Edeline
Contact Person Email
j.edeline@rennes.unicancer.fr

Spain

Earliest CTIS Part Ii Submission Date
11-11-2024
Latest Decision Or Authorization Date
03-12-2025
Processing Time Days
387
Number Of Sites
4
Number Of Participants
32

Sites

Site Name
Hospital Clinico Universitario De Valencia
Department Name
Oncology
Contact Person Name
Desamparados Roda
Contact Person Email
derope@hotmail.com
Site Name
Clinica Universidad De Navarra
Department Name
Oncology
Contact Person Name
Mariano Ponz
Contact Person Email
mponz@unav.es
Site Name
Hospital Universitario 12 De Octubre
Department Name
Oncology
Contact Person Name
Rocío García-Carbonero
Contact Person Email
rgcarbonero@gmail.com
Site Name
Hospital Universitari Vall D Hebron
Department Name
Oncology
Contact Person Name
Jaume Capdevila Castellon
Contact Person Email
jcapdevila@vhio.net

Italy

Earliest CTIS Part Ii Submission Date
18-11-2024
Latest Decision Or Authorization Date
04-12-2025
Processing Time Days
381
Number Of Sites
4
Number Of Participants
40

Sites

Site Name
Istituto Oncologico Veneto
Department Name
Oncologia
Contact Person Name
Sara Lonardi
Contact Person Email
sara.lonardi@iov.veneto.it
Site Name
Fondazione IRCCS Istituto Nazionale Dei Tumori
Department Name
Oncologia Medica
Contact Person Name
Filippo Pietrantonio
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
Istituto Europeo Di Oncologia S.r.l.
Department Name
Oncologia Medica Gastrointestinale e Tumori Neuroendocrini
Contact Person Name
Nicola Fazio
Contact Person Email
nicola.fazio@ieo.it

Germany

Earliest CTIS Part Ii Submission Date
17-11-2024
Latest Decision Or Authorization Date
03-12-2025
Processing Time Days
381
Number Of Sites
4
Number Of Participants
32

Sites

Site Name
Universitaetsklinikum Heidelberg AöR
Department Name
National Center of Tumor Diseases (NCT), Department of Medical Oncology
Contact Person Name
Christoph Springfeld
Site Name
Universitaetsklinikum Ulm AöR
Department Name
Internal Medicine, Center for Internal Medicne Ulm Universitys
Contact Person Name
Thomas Seufferlein
Site Name
Klinikum der Universitaet Muenchen AöR
Department Name
Hematology/ Oncology, Medizinische Klinik III, University Hospital LMU Munich
Contact Person Name
Sabrina Opatz
Site Name
Charite Universitaetsmedizin Berlin KöR
Department Name
Hematology, Oncology, Tumorimmunology
Contact Person Name
Annabel Alig
Contact Person Email
annabel.alig@charite.de

Sponsor

Primary sponsor

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

Contract research organisations

Name
IQVIA Limited
Responsibilities
Operational support functions (roles indicated by sponsor duties codes 1, 12, 2, 5)
Name
Suvoda LLC
Responsibilities
Clinical systems/quality support (sponsor duty code 3)
Name
PPD Global Central Labs
Responsibilities
Central laboratory services
Name
Medidata Solutions Inc.
Responsibilities
ePRO
Name
Perceptive Informatics Inc.
Responsibilities
Central imaging review
Name
Cytel Inc.
Responsibilities
IDMC (independent data monitoring committee) support/statistics

Third parties

  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central imaging review","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central laboratory","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Medidata Solutions Inc.","duties_or_roles":"ePRO","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"CDx analytical and clinical validation","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Cytel Inc.","duties_or_roles":"IDMC","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Azenta US Inc.","duties_or_roles":"Long term sample storage","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"PK sample analysis","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Foundation Medicine Inc.","duties_or_roles":"CDx analytical and clinical validation","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Aperio Clinical Outcomes LLC","duties_or_roles":"","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
Route
ORAL

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