Clinical trial NCT06162221: Study of RAS(ON) Inhibitor Combinations in Patients With Advanced RAS-mutated NSCLC
Official title: A Platform Study of RAS(ON) Inhibitor Combinations in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
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
RAS G12D-mutated NSCLC
Keywords: NSCLC
KRAS G12C
RAS Mutation
KRAS G12X
Non-Small Cell Lung Cancer
Lung Cancer
Lung Cancer Stage IV
Advanced Solid Tumor
Cancer
RAS G12D
Lead sponsor: Revolution Medicines, Inc.
Sponsor class: INDUSTRY
First posted: 2023-12-08
Enrollment: 484
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard(s) of Care (SOC) or with each other.

The first three subprotocols include the following:

Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC

Detailed description: The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents 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), 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)

Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

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)

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.

Primary outcomes:
measure: Adverse events
timeFrame: Up to 5 years
measure: Dose limiting toxicities
timeFrame: 21 days
Secondary outcomes:
measure: Drug concentrations over time
timeFrame: Up to 21 weeks
measure: Cmax
timeFrame: Up to 21 weeks
measure: Tmax
timeFrame: Up to 21 weeks
measure: AUC
timeFrame: Up to 21 weeks
measure: ORR
timeFrame: Up to 5 years
measure: DOR
timeFrame: Up to 5 years
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope - Duarte
state: California
city: Irvine
country: United States
facility: City of Hope - Lennar
state: California
city: Sacramento
country: United States
facility: UC Davis, Davis Comprehensive Cancer Center
state: California
city: San Diego
country: United States
facility: University of California, San Diego Moores Cancer Center
state: California
city: San Francisco
country: United States
facility: UCSF Medical Center - Mission Bay
state: California
city: Stanford
country: United States
facility: Stanford University - Stanford Cancer Institute
state: California
city: Washington
country: United States
facility: Georgetown University Medical Center
state: District of Columbia
city: Plantation
country: United States
facility: Boca Raton Clinical Research Associates
state: Florida
city: St Augustine
country: United States
facility: Cancer Specialists of North Florida
state: Florida
city: Tampa
country: United States
facility: H Lee Moffitt Cancer Center and Research Institute
state: Florida
city: Detroit
country: United States
facility: Henry Ford Cancer - Detroit (Brigitte Harris Cancer Pavilion)
state: Michigan
city: Billings
country: United States
facility: Intermountain Health - St. Vincent Frontier Cancer Center
state: Montana
city: New York
country: United States
facility: New York University Langone Health
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Columbia University Medical Center
state: New York
city: Westbury
country: United States
facility: Clinical Research Alliance
state: New York
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Irving
country: United States
facility: NEXT Oncology Dallas
state: Texas
city: Fairfax
country: United States
facility: NEXT Oncology Virginia
state: Virginia
city: Bron
country: France
facility: Hospices Civils de Lyon - Hôpital Louis Pradel
state: Auvergne-Rhône-Alpes
city: Dijon
country: France
facility: Centre Georges François Leclerc
state: Bourgogne-Franche-Comté
city: Lille
country: France
facility: CHU de Lille Institut Cœur Poumon
state: Hauts-de-France
city: Nantes
country: France
facility: CHU de Nantes
state: Hauts-de-France
city: Bordeaux
country: France
facility: EDOG - Institut Bergonié
state: Nouvelle-Aquitaine
city: Caen
country: France
facility: Centre François Baclesse
city: Suresnes
country: France
facility: Hopital Foch
city: Toulouse
country: France
facility: Oncopole Claudius Regaud
city: Villejuif
country: France
facility: Institut Gustave Roussy
city: Paris
country: France
facility: Institut Curie
state: Île-de-France
city: Berlin
country: Germany
facility: Charite-Universitaetsmedizin Berlin - Campus Charite Mitte
city: Dresden
country: Germany
facility: Universitätsklinikum Carl Gustav Carus an der TU Dresden
city: Frankfurt am Main
country: Germany
facility: Universitätsklinikum Frankfurt
city: Heidelberg
country: Germany
facility: Thoraxklinik Heidelberg gGmbH - Universitätsklinikum Heidelberg
city: Immenhausen
country: Germany
facility: Lungenfachklinik Immenhausen
city: Koln
country: Germany
facility: Uniklinik Köln
city: Moers
country: Germany
facility: Krankenhaus Bethanien Moers
city: Meldola
country: Italy
facility: Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori" - IRST S.r.l
state: Emilia-Romagna
city: Milan
country: Italy
facility: Fondazione IRCCS Istituto Nazionale dei tumori
city: Milan
country: Italy
facility: ASST Grande Ospedale Metropolitano Niguarda
city: Orbassano
country: Italy
facility: A.O.U. San Luigi Gonzaga-Orbassano - SCDU Oncologia Medica
city: Ravenna
country: Italy
facility: Ospedale Santa Maria Delle Croci
city: Rome
country: Italy
facility: IRCCS Instituto Nazionale tumori Ragina Elena
city: Rome
country: Italy
facility: Fondazione Policlinico Universitario A Gemelli-Rome
city: Amsterdam
country: Netherlands
facility: The Netherlands Cancer Institute (NKI)
city: Groningen
country: Netherlands
facility: University Medical Centre Groningen
city: Utrecht
country: Netherlands
facility: University Medical Center Utrecht
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
state: Comunidad de Madrid
city: Pamplona
country: Spain
facility: Clinica Universidad de Navarra
state: Navarre
city: Barcelona
country: Spain
facility: Hospital Universitari Vall D' Hebron
city: Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Madrid
country: Spain
facility: Hospital Clinico San Carlos
city: Madrid
country: Spain
facility: Hospital Universitario Fundacion Jimenez Diaz
city: Malaga
country: Spain
facility: Hospital Regional Universitario de Malaga - Hospital Civil
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio - PPDS
city: Valencia
country: Spain
facility: Fundacion Instituto Valenciano de Oncologia
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe de Valencia
Study officials:
affiliation: Revolution Medicines
name: Revolution Medicines
role: STUDY_DIRECTOR
References: