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Undersøgelse af RMC-6291 i kombination med RMC-6236 hos deltagere med avancerede KRAS G12C mutante solide tumorer

20. september 2026 opdateret af: Revolution Medicines, Inc.

Fase 1b, Multicenter, Open-Label, dosiseskalering og dosisudvidelsesundersøgelse af RMC-6291 i kombination med RMC-6236 hos deltagere med avancerede KRAS G12C mutante solide tumorer

This study is to evaluate the safety, tolerability, and PK profiles of Elironrasib and Daraxonrasib as monotherapies and combination therapy in patients with KRAS G12C-mutated solid tumors.

Studieoversigt

Status

Rekruttering

Betingelser

Intervention / Behandling

Detaljeret beskrivelse

This is an open-label, multicenter, Phase 1b/2 study evaluating elironrasib and daraxonrasib, administered as monotherapy and in combination, in patients with advanced KRAS G12C-mutated solid tumors to determine the maximum tolerated dose (MTD), identify the recommended Phase 2 dose and schedule (RP2DS), and preliminarily assess antitumor activity.

The study includes a Phase 1b dose escalation and expansion of combination therapy, followed by a Phase 2 evaluation of the selected RP2DS as monotherapy and combination therapy to further assess safety and antitumor activity.

Undersøgelsestype

Interventionel

Tilmelding (Anslået)

534

Fase

  • Fase 2
  • Fase 1

Kontakter og lokationer

Dette afsnit indeholder kontaktoplysninger for dem, der udfører undersøgelsen, og oplysninger om, hvor denne undersøgelse udføres.

Studiekontakt

  • Navn: Revolution Medicines, Inc.
  • Telefonnummer: 1-844-2-REVMED
  • E-mail: medinfo@revmed.com

Studiesteder

    • California
      • Duarte, California, Forenede Stater, 91010
        • Trukket tilbage
        • City of Hope
      • Orange, California, Forenede Stater, 92868
        • Rekruttering
        • UC IRVINE Health
      • Sacramento, California, Forenede Stater, 95817
        • Rekruttering
        • UC Davis Comprehensive Cancer Center
      • Stanford, California, Forenede Stater, 94305
        • Rekruttering
        • Stanford Cancer Institute
    • Colorado
      • Aurora, Colorado, Forenede Stater, 80045
        • Rekruttering
        • University of Colorado Cancer Center
    • Florida
      • Sarasota, Florida, Forenede Stater, 34232
        • Rekruttering
        • Florida Cancer Specialists
      • Tampa, Florida, Forenede Stater, 33612
        • Rekruttering
        • Moffitt Cancer Center and Research Institute
    • Indiana
      • Indianapolis, Indiana, Forenede Stater, 46250
        • Rekruttering
        • Community Health Network
    • Massachusetts
      • Boston, Massachusetts, Forenede Stater, 02215
        • Rekruttering
        • Dana Farber Cancer Institute
    • Michigan
      • Detroit, Michigan, Forenede Stater, 48202
        • Trukket tilbage
        • Henry Ford Cancer
      • Grand Rapids, Michigan, Forenede Stater, 49546
        • Rekruttering
        • START Midwest
    • New York
      • New York, New York, Forenede Stater, 10065
        • Rekruttering
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • Columbia University
      • New York, New York, Forenede Stater, 10032
        • Rekruttering
        • NYU Langone Health
    • Oklahoma
      • Oklahoma City, Oklahoma, Forenede Stater, 73104
        • Rekruttering
        • University of Oklahoma
    • Pennsylvania
      • Pittsburgh, Pennsylvania, Forenede Stater, 15212
        • Rekruttering
        • Allegheny Health Network
    • Tennessee
      • Nashville, Tennessee, Forenede Stater, 37203
        • Rekruttering
        • Sarah Cannon Research Institue
    • Texas
      • Dallas, Texas, Forenede Stater, 75230
        • Afsluttet
        • Mary Crowley Cancer Research
      • Houston, Texas, Forenede Stater, 77030
        • Rekruttering
        • MD Anderson
      • Irving, Texas, Forenede Stater, 75039
        • Rekruttering
        • NEXT Dallas
      • San Antonio, Texas, Forenede Stater, 78229
        • Rekruttering
        • NEXT Oncology San Antonio
      • San Antonio, Texas, Forenede Stater, 78229
        • Rekruttering
        • START Texas
    • Virginia
      • Fairfax, Virginia, Forenede Stater, 22031
        • Rekruttering
        • NEXT Oncology Virginia
      • Angers, Frankrig, 49055
        • Rekruttering
        • West Cancer Institute
      • Bordeaux, Frankrig, 33000
        • Rekruttering
        • Institut Bergonie
      • Bron, Frankrig, 69500
        • Rekruttering
        • Hospital Louise Pradel
      • Lille, Frankrig, 59000
        • Rekruttering
        • Oscar Lambret Center of Lillle
      • Lyon, Frankrig, 69373
        • Rekruttering
        • Centre Leon Berard
      • Montpellier, Frankrig, 34298
        • Rekruttering
        • Cancer Institute of Montpellier
      • Nantes, Frankrig, 44093
        • Rekruttering
        • CHU Nantes
      • Strasbourg, Frankrig, 67033
        • Trukket tilbage
        • Institute of Cancer of Strasbourg
      • Amsterdam, Holland, 1066CX
        • Rekruttering
        • Netherlands Cancer Institute Antoni van Leeuwenhoek
      • Ancona, Italien, 60126
        • Rekruttering
        • Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche
      • Aviano, Italien, 33081
        • Rekruttering
        • Centro Di Riferimento Oncologico
      • Meldola, Italien, 47014
        • Rekruttering
        • Institute Romagnolo per lo Studio Tumori
      • Milan, Italien, 20162
        • Rekruttering
        • Niguarda Cancer Center
      • Naples, Italien, 80131
        • Rekruttering
        • Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale"
      • Orbassano, Italien, 10043
        • Rekruttering
        • San Luigi Hospital
      • Ravenna, Italien, 48121
        • Rekruttering
        • AUSL Romagna - S.M. delle Croci Hospital
    • Veneto
      • Verona, Veneto, Italien, 37134
        • Rekruttering
        • Centro Ricerche Cliniche di Verona Srl
    • Puerto Rico
      • San Juan, Puerto Rico, Puerto Rico, 00935
        • Rekruttering
        • Pan American Center for Oncology Trials
      • Barcelona, Spanien, 08023
        • Rekruttering
        • START Barcelona - Hospital HM Nou Delfos
      • Barcelona, Spanien, 08908
        • Rekruttering
        • Institut Catala d'Oncologia Hospital
      • Madrid, Spanien, 28041
        • Rekruttering
        • Hospital Universitario 12 de Octubre
      • Madrid, Spanien, 28027
        • Rekruttering
        • University Clinic of Navarra
      • Madrid, Spanien, 28033
        • Rekruttering
        • Fundacion MD Anderson Cancer Center
      • Madrid, Spanien, 28223
        • Rekruttering
        • NEXT Oncology - Quirónsalud Madrid University Hospital
      • Madrid, Spanien, 28040
        • Rekruttering
        • START Madrid
      • Pamplona, Spanien, 31008
        • Rekruttering
        • University Clinic of Navarra
      • Seville, Spanien, 41009
        • Rekruttering
        • Hospital Universitario Virgen Macarena
      • Valencia, Spanien, 46026
        • Rekruttering
        • La Fe University and Polytechnic Hospital
      • Zaragoza, Spanien, 50009
        • Rekruttering
        • Hospital Universitario Miguel Servet
      • Cologne, Tyskland, 80937
        • Rekruttering
        • Universitäts Klinikum Köln
      • Esslingen am Neckar, Tyskland, 73730
        • Rekruttering
        • Klinikum Esslingen GmbH
      • Moers, Tyskland, 47441
        • Rekruttering
        • Krankenhaus Bethanien Moers
      • Nuremberg, Tyskland, 90419
        • Rekruttering
        • Klinkum Nurnberg Paracelsus Medical Unviersity

Deltagelseskriterier

Forskere leder efter personer, der passer til en bestemt beskrivelse, kaldet berettigelseskriterier. Nogle eksempler på disse kriterier er en persons generelle helbredstilstand eller tidligere behandlinger.

Berettigelseskriterier

Aldre berettiget til at studere

18 år og ældre (Voksen, Ældre voksen)

Tager imod sunde frivillige

Ingen

Køn, der er berettiget til at studere

Alle

Beskrivelse

Inclusion Criteria:

  • 18 years of age

  • Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy

    1. Phase 1b Dose Escalation: solid tumors, previously treated
    2. Phase 1b Dose Expansion and Phase 2:

    i. NSCLC, previously treated with immunotherapy, chemotherapy, and KRAS G12C (OFF) inhibitors ii. Solid tumors, previously treated, naïve to KRAS G12C (OFF) inhibitors.

  • ECOG performance status 0 or 1

  • Adequate organ function

Exclusion Criteria:

  • Primary central nervous system (CNS) tumors
  • Active brain metastases
  • Known impairment of GI function that would alter the absorption
  • Major surgical procedures within 28 days or non-study related minor procedures within 7 days of treatment

Studieplan

Dette afsnit indeholder detaljer om studieplanen, herunder hvordan undersøgelsen er designet, og hvad undersøgelsen måler.

Hvordan er undersøgelsen tilrettelagt?

Design detaljer

  • Primært formål: Behandling
  • Tildeling: Ikke-randomiseret
  • Interventionel model: Sekventiel tildeling
  • Maskning: Ingen (Åben etiket)

Våben og indgreb

Deltagergruppe / Arm
Intervention / Behandling
Eksperimentel: Elironrasib Monotherapy

Phase 2 only

oral tablets

Andre navne:
  • RMC-6291
Eksperimentel: Daraxonrasib Monotherapy

Phase 2 only

oral tablets

Andre navne:
  • RMC-6236
Eksperimentel: Daraxonrasib + Elironrasib Combination

Phase 1b and 2

oral tablets

Andre navne:
  • RMC-6291

oral tablets

Andre navne:
  • RMC-6236

Hvad måler undersøgelsen?

Primære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Number of patients with adverse events (AEs) in Phase 1b
Tidsramme: Up to approximately 3 years

Incidence and severity of treatment-emergent AEs and serious AEs as assessed by Common Terminology Criteria for Adverse Events (CTCAE) v5

Up to approximately 3 years
Changes in vital signs in Phase 1b
Tidsramme: Up to approximately 3 years

Number of patients with clinically significant changes in vital signs

Up to approximately 3 years
Changes in clinical laboratory test values in Phase 1b
Tidsramme: Up to approximately 3 years

Number of patients with clinically significant changes in clinical laboratory test values

Up to approximately 3 years
Dose Limiting Toxicities in Phase 1b
Tidsramme: 21 days

Number of participants with dose limiting toxicities

21 days
Changes in ECGs in Phase 1b
Tidsramme: Up to approximately 3 years

Number of patients with clinically significant changes in ECGs

Up to approximately 3 years
Overall Response Rate (ORR) in Phase 2
Tidsramme: Up to approximately 3 years

Overall response rate per RECIST v1.1 as assessed by blinded independent central review (BICR)

Up to approximately 3 years

Sekundære resultatmål

Resultatmål
Foranstaltningsbeskrivelse
Tidsramme
Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks

Cmax

up to 21 weeks
Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks

Tmax

up to 21 weeks
Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks

AUC

up to 21 weeks
Elimination Half-Life of Elironrasib and Daraxonrasib
Tidsramme: up to 21 weeks

t1/2

up to 21 weeks
Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing
Tidsramme: up to 21 weeks

accumulation ratio

up to 21 weeks
Overall Response Rate (ORR) in Phase 1b
Tidsramme: Up to approximately 3 years

Overall response rate per RECIST v1.1

Up to approximately 3 years
Duration of Response (DOR)
Tidsramme: Up to approximately 3 years

Duration of response per RECIST v1.1

Up to approximately 3 years
Disease Control Rate in Phase 1b
Tidsramme: Up to approximately 3 years

Disease Control rate per RECIST v1.1

Up to approximately 3 years
Time to Response (TTR) in Phase 1b
Tidsramme: Up to approximately 3 years

Time to response per RECIST v1.1

Up to approximately 3 years
Progression-Free Survival (PFS)
Tidsramme: Up to approximately 3 years

Progression-free survival per RECIST v1.1

Up to approximately 3 years
Number of patients with AEs in Phase 2
Tidsramme: Up to approximately 3 years

Incidence and severity of treatment-emergent AEs and serious AEs as assessed by CTCAE v5

Up to approximately 3 years
Changes in vital signs in Phase 2
Tidsramme: Up to approximately 3 years

Number of patients with clinically significant changes in vital signs

Up to approximately 3 years
Changes in clinical laboratory values in Phase 2
Tidsramme: Up to approximately 3 years

Number of patients with clinically significant changes in clinical laboratory test values

Up to approximately 3 years
Overall Survival (OS) in Phase 2
Tidsramme: Up to approximately 3 years

OS is defined as time from enrollment until death from any cause

Up to approximately 3 years

Samarbejdspartnere og efterforskere

Det er her, du vil finde personer og organisationer, der er involveret i denne undersøgelse.

Sponsor

Efterforskere

  • Studieleder: Revolution Medicines, Inc., Revolution Medicines, Inc.

Publikationer og nyttige links

Den person, der er ansvarlig for at indtaste oplysninger om undersøgelsen, leverer frivilligt disse publikationer. Disse kan handle om alt relateret til undersøgelsen.

Datoer for undersøgelser

Disse datoer sporer fremskridtene for indsendelser af undersøgelsesrekord og resumeresultater til ClinicalTrials.gov. Studieregistreringer og rapporterede resultater gennemgås af National Library of Medicine (NLM) for at sikre, at de opfylder specifikke kvalitetskontrolstandarder, før de offentliggøres på den offentlige hjemmeside.

Studer store datoer

Studiestart (Faktiske)

14. november 2023

Primær færdiggørelse (Anslået)

1. december 2028

Studieafslutning (Anslået)

1. juni 2029

Datoer for studieregistrering

Først indsendt

7. november 2023

Først indsendt, der opfyldte QC-kriterier

7. november 2023

Først opslået (Faktiske)

13. november 2023

Opdateringer af undersøgelsesjournaler

Sidste opdatering sendt (Faktiske)

22. september 2026

Sidste opdatering indsendt, der opfyldte kvalitetskontrolkriterier

20. september 2026

Sidst verificeret

1. september 2026

Mere information

Begreber relateret til denne undersøgelse

Andre undersøgelses-id-numre

  • RMC-6291-101

Plan for individuelle deltagerdata (IPD)

Planlægger du at dele individuelle deltagerdata (IPD)?

INGEN

Lægemiddel- og udstyrsoplysninger, undersøgelsesdokumenter

Studerer et amerikansk FDA-reguleret lægemiddelprodukt

Ja

Studerer et amerikansk FDA-reguleret enhedsprodukt

Ingen

Disse oplysninger blev hentet direkte fra webstedet clinicaltrials.gov uden ændringer. Hvis du har nogen anmodninger om at ændre, fjerne eller opdatere dine undersøgelsesoplysninger, bedes du kontakte register@clinicaltrials.gov. Så snart en ændring er implementeret på clinicaltrials.gov, vil denne også blive opdateret automatisk på vores hjemmeside .