Clinical trial • Phase I/II • Oncology|Respiratory

(chemical described in product record) for Non-small cell lung cancer|RAS‑mutated non-small cell lung cancer

Phase I/II trial of (chemical described in product record) for Non-small cell lung cancer|RAS‑mutated non-small cell lung cancer. open-label, adaptive.

Overview

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

Key dates

Initial CTIS Submission Date
11-03-2024
First CTIS Authorization Date
25-06-2024

Trial design

open-label, adaptive Phase I/II trial in Netherlands, Spain, Italy and others.

Open Label
Yes
Adaptive
True, includes dose-escalation/safety lead-in elements (DLT assessment and dose-escalation rules / safety lead-in cohorts as indicated by primary endpoint on DLTs and a dose escalation simulation report document).
Biomarker Stratified
True, biomarker: RAS mutation (RAS‑mutated NSCLC)
Single Multiple Or Escalation Dose Combined
Yes
Target Sample Size
176

Eligibility

Recruits 176 Vulnerable population selected. Subject information and informed consent forms (ICFs) are provided (country-specific ICFs listed for NL, ES, IT, DE, FR, etc.) and there are pregnancy/pregnant-partner ICFs available. Participants are adults (≥18 years) so consent is provided by the participant; no assent procedures for minors are specified..

Vulnerable Population
Vulnerable population selected. Subject information and informed consent forms (ICFs) are provided (country-specific ICFs listed for NL, ES, IT, DE, FR, etc.) and there are pregnancy/pregnant-partner ICFs available. Participants are adults (≥18 years) so consent is provided by the participant; no assent procedures for minors are specified.

Inclusion criteria

  • {"criterion_text":"- Patients that are at least 18 years old.\n- Patients that have NSCLC with certain RAS mutations.\n- Patients that have NSCLC that is unlikely to be cured and has spread to other body parts.\n- Patients that have received prior cancer treatment.\n- Patients that have at least one tumor lesion (an area of abnormal tissue) that can be measured.\n- Patients that have adequate organ function (bone marrow, liver, kidney)."}

Exclusion criteria

  • {"criterion_text":"- 1. Participants that have primary brain and spinal cord tumor spreading to other body parts.\n- 2. Participants that have gastrointestinal problems that may affect absorption of RMC-6236.\n- 3. Participants that had any major surgery in the last 4 weeks.\n- 4. Participants that have have previously taken targeted therapy for RAS mutation.\n- 5. Participants that have any other medical condition that may interfere with the study drugs."}

Endpoints

Primary endpoints

  • {"endpoint_text":"- • Incidence of DLTs (Part 1 and Part 2 Cohort 2 safety lead-in only)","definition_or_measurement_approach":"Incidence of dose-limiting toxicities (DLTs) assessed during the specified safety lead-in periods (Part 1 and Part 2 Cohort 2)."}
  • {"endpoint_text":"- •Incidence of TEAEs, TRAEs, SAEs, and clinically significant changes in laboratory test values, ECGs, and vital signs","definition_or_measurement_approach":"Incidence of treatment-emergent adverse events (TEAEs), treatment-related adverse events (TRAEs), serious adverse events (SAEs), and clinically significant changes detected by laboratory tests, ECGs, and vital signs monitoring."}

Secondary endpoints

  • {"endpoint_text":"- • Concentrations of RMC-6236 in plasma over time and PK parameters as applicable.","definition_or_measurement_approach":"Plasma pharmacokinetic (PK) sampling of RMC-6236 over time with derivation of standard PK parameters (e.g., Cmax, AUC) 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 according to RECIST v1.1 criteria."}

Recruitment

Planned Sample Size
176
Recruitment Window Months
17
Consent Approach
Informed consent obtained from participants (participants are adults ≥18). Country-specific subject information sheets and ICFs are provided (documents available in Dutch, Spanish, Italian, German, French, English, etc.). Separate pregnancy/pregnant-partner ICFs are available where applicable.

Geography

Total Number Of Sites
42
Total Number Of Participants
180

Netherlands

Earliest CTIS Part Ii Submission Date
31-05-2024
Latest Decision Or Authorization Date
14-08-2024
Processing Time Days
75
Number Of Sites
4
Number Of Participants
36

Sites

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

Spain

Earliest CTIS Part Ii Submission Date
29-05-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
33
Number Of Sites
13
Number Of Participants
36

Sites

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

Italy

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
26-06-2024
Processing Time Days
27
Number Of Sites
7
Number Of Participants
36

Sites

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

Germany

Earliest CTIS Part Ii Submission Date
14-06-2024
Latest Decision Or Authorization Date
06-08-2024
Processing Time Days
53
Number Of Sites
7
Number Of Participants
36

Sites

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

France

Earliest CTIS Part Ii Submission Date
30-05-2024
Latest Decision Or Authorization Date
01-07-2024
Processing Time Days
32
Number Of Sites
11
Number Of Participants
36

Sites

Site Name
Oncopole Claudius Regaud
Department Name
Medical Oncology Department
Principal Investigator Name
Audrey RABEAU
Principal Investigator Email
Rabeau.audrey@iuct-oncopole.fr
Contact Person Name
Audrey RABEAU
Contact Person Email
Rabeau.audrey@iuct-oncopole.fr
Site Name
Centre Francois Baclesse
Principal Investigator Name
Hubert CURCIO
Principal Investigator Email
h.curcio@baclesse.unicancer.fr
Contact Person Name
Hubert CURCIO
Contact Person Email
h.curcio@baclesse.unicancer.fr
Site Name
Hospital Foch
Principal Investigator Name
Jaafar BENNOUNA
Principal Investigator Email
j.bennouna@hopital-foch.com
Contact Person Name
Jaafar BENNOUNA
Contact Person Email
j.bennouna@hopital-foch.com
Site Name
Institut Bergonie
Principal Investigator Name
Sophie COUSIN
Principal Investigator Email
s.cousin@bordeaux-unicancer.fr
Contact Person Name
Sophie COUSIN
Contact Person Email
s.cousin@bordeaux-unicancer.fr
Site Name
Centre Hospitalier Universitaire De Lille
Principal Investigator Name
Alexis CORTOT
Principal Investigator Email
Alexis.cortot@chru-lille.fr
Contact Person Name
Alexis CORTOT
Contact Person Email
Alexis.cortot@chru-lille.fr
Site Name
Institut Gustave Roussy
Department Name
DITEP (Medical Oncology in Early Drug Development Department)
Principal Investigator Name
Anas GAZZAH
Principal Investigator Email
anas.gazzah@gustaveroussy.fr
Contact Person Name
Anas GAZZAH
Contact Person Email
anas.gazzah@gustaveroussy.fr
Site Name
Hospices Civils De Lyon
Principal Investigator Name
Michael DURUISSEAUX
Principal Investigator Email
Michael.duruisseaux@chu-lyon.fr
Contact Person Name
Michael DURUISSEAUX
Site Name
Institut Curie
Principal Investigator Name
Pauline DU RUSQUEC
Principal Investigator Email
Pauline.durusquec@curie.fr
Contact Person Name
Pauline DU RUSQUEC
Contact Person Email
Pauline.durusquec@curie.fr
Site Name
Centre Hospitalier Universitaire De Nantes
Principal Investigator Name
Jeanne CHEN
Principal Investigator Email
Jeanne.chen@chu-nantes.fr
Contact Person Name
Jeanne CHEN
Contact Person Email
Jeanne.chen@chu-nantes.fr
Site Name
Centr Georges Francois Leclerc
Principal Investigator Name
François GHIRINGHELLI
Principal Investigator Email
fghiringhelli@cgfl.fr
Contact Person Name
François GHIRINGHELLI
Contact Person Email
fghiringhelli@cgfl.fr
Site Name
Centre Francois Baclesse (additional listing)

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.

Third parties

  • {"country":"United States","full_name":"Discovery Life Sciences LLC","duties_or_roles":"code 4","organisation_type":"Laboratory/Research/Testing facility"}
  • {"country":"United States","full_name":"Propharma Group LLC","duties_or_roles":"code 9","organisation_type":"Pharmaceutical company"}
  • {"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":"Sherpa Clinical Packaging LLC","duties_or_roles":"Collect and read ECG scans","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Aperio Clinical Outcomes LLC","duties_or_roles":"code 6","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central Imaging","organisation_type":"Pharmaceutical company"}
  • {"country":"United Kingdom","full_name":"Primevigilance Limited","duties_or_roles":"code 8","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":"United States","full_name":"Atreo Inc.","duties_or_roles":"code 3","organisation_type":"Non-Pharmaceutical company"}
  • {"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":"Edetek Inc.","duties_or_roles":"Stats Programing","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Adaptive Biotechnologies Corp.","duties_or_roles":"code 4","organisation_type":"Pharmaceutical company"}
  • {"country":"United States","full_name":"Tempus Labs Inc.","duties_or_roles":"code 4","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":"Medidata Solutions Inc.","duties_or_roles":"Electronic drug diaries","organisation_type":"Non-Pharmaceutical company"}
  • {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ctDNA Analysis","organisation_type":"Laboratory/Research/Testing facility"}

Investigational products

Investigational Product Name
DARAXONRASIB (RMC-6236)
Active Substance
(chemical described in product record)
Modality
Small molecule
Routes Of Administration
ORAL
Route
ORAL
Authorisation Status
1
Maximum Dose
400 mg
Investigational Product Name
KEYTRUDA (pembrolizumab)
Active Substance
PEMBROLIZUMAB
Modality
Monoclonal antibody
Routes Of Administration
SOLUTION FOR INFUSION (intravenous infusion)
Route
Intravenous infusion
Authorisation Status
2
Maximum Dose
200 mg
Investigational Product Name
Pemetrexed (various brands)
Active Substance
PEMETREXED
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
Intravenous infusion
Authorisation Status
2
Maximum Dose
500 mg total (maxTotalDoseAmount indicates 500 mg total or 23.8 mg/m2 daily as provided)
Investigational Product Name
Cisplatin (various brands)
Active Substance
CISPLATIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
Intravenous infusion
Authorisation Status
2
Maximum Dose
75 mg (maxTotalDoseAmount 75 or maxDailyDoseAmount 3.57 mg/m2 as provided)
Investigational Product Name
Carboplatin (various brands)
Active Substance
CARBOPLATIN
Modality
Small molecule
Routes Of Administration
SOLUTION FOR INFUSION
Route
Intravenous infusion
Authorisation Status
2
Maximum Dose
750 mg (maxTotalDoseAmount 750 or maxDailyDoseAmount as provided)
Combination Treatment
Yes

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