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Recruiting NCT06128551

Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Participants With Advanced KRAS G12C Mutant Solid Tumors

Phase I / Phase II Interventional Non-Small Cell Lung Cancer (NSCLC) Colorectal Cancer Pancreatic Ductal Adenocarcinoma

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: Elironrasib, Daraxonrasib.
Who it may be relevant to
Registry conditions: Non-Small Cell Lung Cancer (NSCLC), Colorectal Cancer, Pancreatic Ductal Adenocarcinoma. 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, France, Germany, Italy, Netherlands +2
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

Phase 1b/2, Multicenter, Open-label, Dose Escalation and Dose Expansion Study of Elironrasib and Daraxonrasib as Monotherapies and Combination Therapy in Patients With Advanced KRAS G12C-Mutated Solid Tumors

Overview

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.

Detailed description

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.

Interventions

  • Drug Elironrasib
    oral tablets
  • Drug Daraxonrasib
    oral tablets

Primary outcome measures

  • Number of patients with adverse events (AEs) in Phase 1b [Time frame: Up to approximately 3 years]
  • Changes in vital signs in Phase 1b [Time frame: Up to approximately 3 years]
  • Changes in clinical laboratory test values in Phase 1b [Time frame: Up to approximately 3 years]
  • Dose Limiting Toxicities in Phase 1b [Time frame: 21 days]
  • Changes in ECGs in Phase 1b [Time frame: Up to approximately 3 years]
  • Overall Response Rate (ORR) in Phase 2 [Time frame: Up to approximately 3 years]
Secondary outcome measures (12)
  • Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib [Time frame: up to 21 weeks]
  • Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib [Time frame: up to 21 weeks]
  • Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib [Time frame: up to 21 weeks]
  • Elimination Half-Life of Elironrasib and Daraxonrasib [Time frame: up to 21 weeks]
  • Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing [Time frame: up to 21 weeks]
  • Overall Response Rate (ORR) in Phase 1b [Time frame: Up to approximately 3 years]
  • Duration of Response (DOR) [Time frame: Up to approximately 3 years]
  • Disease Control Rate in Phase 1b [Time frame: Up to approximately 3 years]
  • Time to Response (TTR) in Phase 1b [Time frame: Up to approximately 3 years]
  • Progression-Free Survival (PFS) [Time frame: Up to approximately 3 years]
  • Number of patients with AEs in Phase 2 [Time frame: Up to approximately 3 years]
  • Changes in vital signs in Phase 2 [Time frame: Up to approximately 3 years]

Eligibility criteria

Inclusion criteria

  • 18 years of age
  • Histology: pathologically documented, KRAS G12C-mutated, advanced or metastatic solid tumors not amendable to curative therapy
  • Phase 1b Dose Escalation: solid tumors, previously treated
  • 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

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
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 23 centers
  • City of Hope — Duarte
  • UC IRVINE Health — Orange
  • UC Davis Comprehensive Cancer Center — Sacramento
  • Stanford Cancer Institute — Stanford
  • University of Colorado Cancer Center — Aurora
  • Florida Cancer Specialists — Sarasota
  • Moffitt Cancer Center and Research Institute — Tampa
  • Community Health Network — Indianapolis
  • … and 15 more centers
Spain · 11 centers
  • START Barcelona - Hospital HM Nou Delfos — Barcelona
  • Institut Catala d'Oncologia Hospital — Barcelona
  • University Clinic of Navarra — Madrid
  • Fundacion MD Anderson Cancer Center — Madrid
  • START Madrid — Madrid
  • Hospital Universitario 12 de Octubre — Madrid
  • NEXT Oncology - Quirónsalud Madrid University Hospital — Madrid
  • University Clinic of Navarra — Pamplona
  • … and 3 more centers
France · 8 centers
  • West Cancer Institute — Angers
  • Institut Bergonie — Bordeaux
  • Hospital Louise Pradel — Bron
  • Oscar Lambret Center of Lillle — Lille
  • Centre Leon Berard — Lyon
  • Cancer Institute of Montpellier — Montpellier
  • CHU Nantes — Nantes
  • Institute of Cancer of Strasbourg — Strasbourg
Italy · 7 centers
  • Department of Medical Oncology - Azienda Ospedaliero Uniersitaria delle Marche — Ancona
  • Centro Di Riferimento Oncologico — Aviano
  • Institute Romagnolo per lo Studio Tumori — Meldola
  • Niguarda Cancer Center — Milan
  • Istituto Nazionale Tumori IRCCS Fondazione "G. Pascale" — Naples
  • San Luigi Hospital — Orbassano
  • AUSL Romagna - S.M. delle Croci Hospital — Ravenna
Germany · 4 centers
  • Universitäts Klinikum Köln — Cologne
  • Klinikum Esslingen GmbH — Esslingen am Neckar
  • Krankenhaus Bethanien Moers — Moers
  • Klinkum Nurnberg Paracelsus Medical Unviersity — Nuremberg
Netherlands · 1 center
  • Netherlands Cancer Institute Antoni van Leeuwenhoek — Amsterdam
Puerto Rico · 1 center
  • Pan American Center for Oncology Trials — San Juan

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: NCT06128551 · RMC-6291-101

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗