Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: RMC-6291, RMC-6236, Pembrolizumab, Cisplatin.
- Who it may be relevant to
- Registry conditions: Non-Small Cell Lung Cancer, NSCLC, KRAS, NRAS, HRAS-mutated NSCLC, KRAS G12C-mutated Solid Tumors, Lung Cancer, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States, Australia, Austria, Czechia, Denmark +8
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Unsure about the terms? Read our patient guide →
Official title
A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
Overview
The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other. The first four subprotocols include the following: Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805
Detailed description
The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents or as a monotherapy to be evaluated in patients with RAS-mutated solid tumors with a focus on NSCLC.
This is an open-label platform Phase 1b/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC), or as a monotherapy and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with KRAS or RAS mutations will be specified in each subprotocol.
Subprotocol A is an open-label, multicenter, Phase 1b/2 study of RMC-6291, with or without RMC-6236, in combination with pembrolizumab, with or without chemotherapy, in patients with KRAS G12C-mutated advanced solid tumors.
Subprotocol B is an open-label, multicenter, Phase1b/2 study of RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with RAS-mutated non-small cell lung cancer (NSCLC)
Subprotocol C is an open-label, multicenter, Phase1b/2 study of RMC-9805 with or without RMC-6236, in combination with other anticancer agents, in patients with RAS G12D-mutated non-small cell lung cancer (NSCLC)
Subprotocol D is a Phase 2, Open-label, Multicenter Study of Zoldonrasib (RMC-9805) in Previously Treated Patients with RAS G12D-Mutant Non-Small Cell Lung Cancer (NSCLC)
Subprotocols A, B, and C consist of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion. Subprotocol D consists of only one part.
Interventions
- Drug RMC-6291
Oral tablet - Drug RMC-6236
Oral tablet - Drug Pembrolizumab
IV Infusion - Drug Cisplatin
IV Infusion - Drug Carboplatin
IV Infusion - Drug Pemetrexed
IV infusion - Drug RMC-9805
Oral Tablet
Primary outcome measures
- Adverse events [Time frame: Up to 5 years]
- Dose limiting toxicities [Time frame: 21 days]
Secondary outcome measures (6)
- Drug concentrations over time [Time frame: Up to 21 weeks]
- Cmax [Time frame: Up to 21 weeks]
- Tmax [Time frame: Up to 21 weeks]
- AUC [Time frame: Up to 21 weeks]
- ORR [Time frame: Up to 5 years]
- DOR [Time frame: Up to 5 years]
Eligibility criteria
Inclusion criteria
All Patients (unless otherwise noted):
- ≥ 18 years of age
- ECOG PS is 0 to 1
- Adequate organ function as outlined by the study
- Received prior standard therapy appropriate for tumor type and stage
- Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A)
- Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)
- Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D)
Exclusion criteria
All Patients:
- Primary central nervous system (CNS) tumors
- Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
- Major surgery < 28 days of first dose
- Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids
Other inclusion/exclusion criteria may apply.
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- Non-randomized
- Model
- Parallel assignment
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 28 centers
- Banner MD Anderson Cancer Center — Gilbert
- City of Hope - Duarte — Duarte
- City of Hope - Lennar — Irvine
- UC Davis, Davis Comprehensive Cancer Center — Sacramento
- University of California, San Diego Moores Cancer Center — San Diego
- UCSF Medical Center - Mission Bay — San Francisco
- Stanford University - Stanford Cancer Institute — Stanford
- Colorado Health Medical Group - Medical Oncology & Hematology — Colorado Springs
- … and 20 more centers
France · 14 centers
- Hospices Civils de Lyon - Hôpital Louis Pradel — Bron
- Centre Georges François Leclerc — Dijon
- CHU de Lille Institut Cœur Poumon — Lille
- CHU de Nantes — Nantes
- EDOG - Institut Bergonié — Bordeaux
- Institut de Cancerologie de Ouest (ICO) - Angers — Angers
- Ambroise-Paré Hospital — Boulogne
- Centre François Baclesse — Caen
- … and 6 more centers
Spain · 12 centers
- Hospital Clinico San Carlos — Madrid
- Hospital Universitario 12 de Octubre — Madrid
- Clinica Universidad de Navarra — Pamplona
- Hospital Universitari i Politecnic La Fe de Valencia — Valencia
- … and 8 more centers
Germany · 7 centers
- Charite-Universitaetsmedizin Berlin - Campus Charite Mitte — Berlin
- Uniklinik Köln — Cologne
- Universitätsklinikum Carl Gustav Carus an der TU Dresden — Dresden
- Universitätsklinikum Frankfurt — Frankfurt am Main
- Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg — Heidelberg
- Lungenfachklinik Immenhausen — Immenhausen
- Krankenhaus Bethanien Moers — Moers
Italy · 7 centers
- Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l — Meldola
- Fondazione IRCCS Istituto Nazionale dei tumori — Milan
- ASST Grande Ospedale Metropolitano Niguarda — Milan
- A.O.U. San Luigi Gonzaga-Orbassano - SCDU Oncologia Medica — Orbassano
- Ospedale Santa Maria Delle Croci — Ravenna
- IRCCS Instituto Nazionale tumori Ragina Elena — Rome
- Fondazione Policlinico Universitario A Gemelli-Rome — Rome
Australia · 5 centers
- Chris O'Brien Lifehouse Hosptial — Camperdown
- Liverpool Hospital — Liverpool
- Royal North Shore Hospital — St Leonards
- Monash Health — Clayton
- Linear Clinical Research — Nedlands
South Korea · 5 centers
- Samsung Medical Center — Seoul
- National Cancer Center — Goyang-si
- Seoul National University Bundang Hospital — Seongnam-si
- Seoul St. Mary's Hospital, The Catholic University of Korea — Seoul
- Severance Hospital — Seoul
Taiwan · 5 centers
Center list to be confirmed — check the primary protocol.
Netherlands · 4 centers
- The Netherlands Cancer Institute (NKI) — Amsterdam
- University Medical Centre Groningen — Groningen
- Leiden University Medical Center — Leiden
- University Medical Center Utrecht — Utrecht
Denmark · 2 centers
- Rigshospitalet — Copenhagen
- Odense University Hospital, Department of Oncology — Odense
Greece · 2 centers
- Henry Dunant Hospital Center — Athens
- Thoracic General Hospital of Athens "I SOTIRIA" — Athens
Austria · 1 center
- Universitätsklinikum St. Pölten — Sankt Pölten
Czechia · 1 center
- Nemocnice AGEL Novy Jicin a.s — Nový Jičín
Publications
- Cregg J, Edwards AV, Chang S, Lee BJ, Knox JE, Tomlinson ACA, Marquez A, Liu Y, Freilich R, Aay N, Wang Y, Jiang L, Jiang J, Wang Z, Flagella M, Wildes D, Smith JAM, Singh M, Wang Z, Gill AL, Koltun ES. Discovery of Daraxonrasib (RMC-6236), a Potent and Orally Bioavailable RAS(ON) Multi-selective, Noncovalent Tri-complex Inhibitor for the Treatment of Patients with Multiple RAS-Addicted Cancers. J PMID 40056080
Identifiers
NCT: NCT06162221 · RMC-LUNG-101