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 Non-small cell lung cancer
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
- Non-small cell lung cancer
- Trial Stage
- Phase III
- Drug Modality
- Small molecule
Key dates
- Initial CTIS Submission Date
- 10-03-2025
- First CTIS Authorization Date
- 01-07-2025
Trial design
Randomised, open-label, docetaxel (product name docetaxel), solution for infusion, route: intravenous use; dose information provided: max daily dose 75 mg/m2 (doseuom: mg/m2).-controlled Phase III trial across 86 sites in Belgium, Germany, Ireland and others.
- Randomised
- Yes
- Open Label
- Yes
- Comparator
- Docetaxel (product name DOCETAXEL), solution for infusion, route: intravenous use; dose information provided: max daily dose 75 mg/m2 (doseUom: mg/m2).
- Target Sample Size
- 124
Eligibility
Recruits 124 Vulnerable population selected. Consent is required from participants (minimum age 18). Subject information and informed consent forms (Pre-screening ICF, Main ICF, Pregnant Partner ICF and related documents) are provided and available in multiple country/language versions (examples in English, French, Dutch, German, Italian, Spanish, Polish) as per the submitted ICF documents..
- Pregnancy Exclusion
- Pregnant or breastfeeding
- Vulnerable Population
- Vulnerable population selected. Consent is required from participants (minimum age 18). Subject information and informed consent forms (Pre-screening ICF, Main ICF, Pregnant Partner ICF and related documents) are provided and available in multiple country/language versions (examples in English, French, Dutch, German, Italian, Spanish, Polish) as per the submitted ICF documents.
Inclusion criteria
- {"criterion_text":"- At least 18 years of age and has provided informed consent."}
- {"criterion_text":"- ECOG performance status 0 or 1."}
- {"criterion_text":"- Pathologically confirmed NSCLC, either locally advanced or metastatic, not amenable to curative surgery or radiotherapy"}
- {"criterion_text":"- Measurable disease per RECIST v1.1"}
- {"criterion_text":"- Adequate organ function (bone marrow, liver, kidney, coagulation)"}
- {"criterion_text":"- One to two prior lines of therapy including an anti-PD-1/anti-PD(L)-1 agent and platinum-based chemotherapy."}
- {"criterion_text":"- Documented RAS mutation status, defined as nonsynonymous mutations in KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)"}
- {"criterion_text":"- Able to take oral medications"}
- {"criterion_text":"- For the full list of inclusion criteria please refer to the protocol."}
Exclusion criteria
- {"criterion_text":"- Prior therapy with any direct RAS-targeted therapy or docetaxel"}
- {"criterion_text":"- Untreated central nervous system (CNS) metastases"}
- {"criterion_text":"- Medically significant comorbidities (significant cardiovascular disease, lung disease, or impaired GI function)"}
- {"criterion_text":"- Ongoing anticancer therapy"}
- {"criterion_text":"- Pregnant or breastfeeding"}
- {"criterion_text":"- For the full list of exclusion criteria please refer to the protocol."}
Endpoints
Primary endpoints
- {"endpoint_text":"- PFS is defined as time from randomization until disease progression or death from any cause, whichever occurs first. Progression is per RECIST v1.1 as assessed by Investigator. OS is defined as time from randomization until death from any cause.","definition_or_measurement_approach":"PFS: time from randomization until disease progression or death from any cause; progression assessed per RECIST v1.1 by Investigator. OS: time from randomization until death from any cause."}
Recruitment
- Registry Or Advocacy Recruitment
- True: Patient Advocacy Group (patient advocacy engagement materials included in recruitment documentation; specific advocacy organisation names not specified in documents).
- Digital Remote Recruitment
- True: Digital methods documented include banner ads, digital waiting room ads, social media posts, and other digital patient-facing recruitment materials (country-specific digital recruitment materials present).
- Planned Sample Size
- 124
- Recruitment Window Months
- 64
- Consent Approach
- Participants must be at least 18 years old and provide informed consent themselves. Country-specific informed consent documents are provided (Pre-screening ICF, Main ICF, Pregnant Partner ICF, Optional/Future Research ICF) in multiple languages and versions (examples: English, French, Dutch, German, Italian, Spanish, Polish) as submitted in the ICF documents.
Methods
- Banner Ads (digital) — country-specific versions present (e.g. K2_RecruitMat_Banner Ads).
- Digital Waiting Room Ad — country-specific versions (e.g. K2_RecruitMat_Digital Waiting Room Ad).
- Patient Advocacy Group Letter / Patient Advocacy engagement materials (Patient Advocacy Group Letter).
- Doctor-to-Patient Letter / Physician Referral Letter (Dr-to-Patient Letter, Physician Referral Letter).
- Social media clinical trial posts (K2_RecruitMat_Social Media_Clinical Trial Posts).
- Patient brochures and patient-facing study materials (K2_Patient_Brochure, Patient Study Guide).
- GP/physician templates and GP letter templates (e.g. L2_Ireland GP Letter Template).
- Site-based recruitment via hospital/clinic sites (local site contact details included in Part II submissions).
- Pre-screening materials and Pre-screening ICF to identify eligible patients.
Geography
- Total Number Of Sites
- 86
- Total Number Of Participants
- 296
Belgium
- Earliest CTIS Part Ii Submission Date
- 13-06-2025
- Latest Decision Or Authorization Date
- 01-07-2025
- Processing Time Days
- 18
- Number Of Sites
- 6
- Number Of Participants
- 22
Sites
- Site Name
- Universitair Ziekenhuis Antwerpen
- Department Name
- Pneumology
- Principal Investigator Name
- Jo Raskin
- Principal Investigator Email
- jo.raskin@uza.be
- Contact Person Name
- Jo Raskin
- Contact Person Email
- jo.raskin@uza.be
- Site Name
- Grand Hopital De Charleroi
- Department Name
- Pneumology
- Principal Investigator Name
- Benoît Colinet
- Principal Investigator Email
- benoit.colinet2@ghdc.be
- Contact Person Name
- Benoît Colinet
- Contact Person Email
- benoit.colinet2@ghdc.be
- Site Name
- Algemeen Ziekenhuis Delta
- Department Name
- Oncology
- Principal Investigator Name
- Ingel Demedts
- Principal Investigator Email
- ingel.demedts@azdelta.be
- Contact Person Name
- Ingel Demedts
- Contact Person Email
- ingel.demedts@azdelta.be
- Site Name
- Institut Jules Bordet
- Department Name
- Medical Oncology
- Principal Investigator Name
- Mariana Brandao
- Principal Investigator Email
- mariana.brandao@hubruxelles.be
- Contact Person Name
- Mariana Brandao
- Contact Person Email
- mariana.brandao@hubruxelles.be
- Site Name
- UZ Leuven
- Department Name
- Pulmonology
- Principal Investigator Name
- Christophe Dooms
- Principal Investigator Email
- christophe.dooms@uzleuven.be
- Contact Person Name
- Christophe Dooms
- Contact Person Email
- christophe.dooms@uzleuven.be
- Site Name
- Algemeen Ziekenhuis Groeninge
- Department Name
- Pneumology
- Principal Investigator Name
- Sofie Derijcke
- Principal Investigator Email
- sofie.derijcke@azgroeninge.be
- Contact Person Name
- Sofie Derijcke
- Contact Person Email
- sofie.derijcke@azgroeninge.be
Germany
- Earliest CTIS Part Ii Submission Date
- 16-06-2025
- Latest Decision Or Authorization Date
- 01-07-2025
- Processing Time Days
- 15
- Number Of Sites
- 11
- Number Of Participants
- 48
Ireland
- Earliest CTIS Part Ii Submission Date
- 06-06-2025
- Latest Decision Or Authorization Date
- 04-07-2025
- Processing Time Days
- 28
- Number Of Sites
- 7
- Number Of Participants
- 15
Italy
- Earliest CTIS Part Ii Submission Date
- 13-06-2025
- Latest Decision Or Authorization Date
- 04-08-2025
- Processing Time Days
- 52
- Number Of Sites
- 16
- Number Of Participants
- 50
Spain
- Earliest CTIS Part Ii Submission Date
- 18-06-2025
- Latest Decision Or Authorization Date
- 04-07-2025
- Processing Time Days
- 16
- Number Of Sites
- 18
- Number Of Participants
- 54
Netherlands
- Earliest CTIS Part Ii Submission Date
- 12-06-2025
- Latest Decision Or Authorization Date
- 07-08-2025
- Processing Time Days
- 56
- Number Of Sites
- 6
- Number Of Participants
- 29
Poland
- Earliest CTIS Part Ii Submission Date
- 16-06-2025
- Latest Decision Or Authorization Date
- 07-07-2025
- Processing Time Days
- 21
- Number Of Sites
- 4
- Number Of Participants
- 14
France
- Earliest CTIS Part Ii Submission Date
- 12-06-2025
- Latest Decision Or Authorization Date
- 04-07-2025
- Processing Time Days
- 22
- Number Of Sites
- 17
- Number Of Participants
- 64
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
- codes: 1,12,2,5
- Name
- Medidata Solutions Inc.
- Responsibilities
- ePROs and target SDV; codes: 15,7
- Name
- Suvoda LLC
- Responsibilities
- code: 3
- Name
- Cytel Inc.
- Responsibilities
- IDMC
Third parties
- {"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":"Medidata Solutions Inc.","duties_or_roles":"ePROs and target SDV; codes: 15,7","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"IQVIA Limited","duties_or_roles":"codes: 1,12,2,5","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Suvoda LLC","duties_or_roles":"code: 3","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":"Belgium","full_name":"PPD Global Central Labs","duties_or_roles":"Central Laboratory","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Perceptive Informatics Inc.","duties_or_roles":"Central imaging review","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"hosting the global safety database for the IMP; pharmacovigilance duties","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":"Cytel Inc.","duties_or_roles":"IDMC","organisation_type":"Non-Pharmaceutical company"}
- {"country":"United States","full_name":"Alturas Analytics Inc.","duties_or_roles":"PK analysis","organisation_type":"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":"Cisys Inc.","duties_or_roles":"system for sites to upload documents for the eligibility review and acknowledgement of patient randomization on study.","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
- Authorisation Status
- prodAuthStatus: 1
- Maximum Dose
- 200 mg (maxDailyDoseAmount)
- Investigational Product Name
- DOCETAXEL
- Active Substance
- Docetaxel
- Modality
- Small molecule
- Routes Of Administration
- Intravenous use
- Route
- INTRAVENOUS
- Authorisation Status
- prodAuthStatus: 2
- Maximum Dose
- 75 mg/m2 (maxDailyDoseAmount)
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