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NCT Number: NCT06128551

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

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.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Adenocarcinoma Adnexal Diseases Appendiceal Neoplasms Bronchial Diseases Bronchial Neoplasms Carcinoma Carcinoma, Bronchogenic Carcinoma, Ductal Carcinoma, Non-Small-Cell Lung Carcinoma, Pancreatic Ductal Cecal Diseases Cecal Neoplasms Colonic Diseases Colonic Neoplasms Colorectal Cancer Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Endocrine Gland Neoplasms Endocrine System Diseases Endometrial Neoplasms Esophageal Diseases Esophageal Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastrointestinal Diseases Gastrointestinal Neoplasms Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Gonadal Disorders Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Lung Diseases Lung Neoplasms Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Ductal, Lobular, and Medullary Neoplasms, Glandular and Epithelial Neoplastic Processes Ovarian Diseases Ovarian Neoplasms Pancreatic Diseases Pancreatic Ductal Adenocarcinoma Pancreatic Neoplasms Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases Rectal Neoplasms Respiratory Tract Diseases Respiratory Tract Neoplasms Stomach Diseases Stomach Neoplasms Thoracic Neoplasms Urogenital Diseases Urogenital Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

West Cancer Institute, Angers, France

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Elironrasib

Drug

oral tablets

Other names: RMC-6291

daraxonrasib

Drug

oral tablets

Other names: RMC-6236

Primary outcomes

  1. Number of patients with adverse events (AEs) in Phase 1b

    Time frame: 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

  2. Changes in vital signs in Phase 1b

    Time frame: Up to approximately 3 years

    Number of patients with clinically significant changes in vital signs

  3. Changes in clinical laboratory test values in Phase 1b

    Time frame: Up to approximately 3 years

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

  4. Dose Limiting Toxicities in Phase 1b

    Time frame: 21 days

    Number of participants with dose limiting toxicities

  5. Changes in ECGs in Phase 1b

    Time frame: Up to approximately 3 years

    Number of patients with clinically significant changes in ECGs

  6. Overall Response Rate (ORR) in Phase 2

    Time frame: Up to approximately 3 years

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

Secondary outcomes

  1. Maximum Observed Blood Concentration of Elironrasib and Daraxonrasib

    Time frame: up to 21 weeks

    Cmax

  2. Time to Reach Maximum Blood Concentration of Elironrasib and Daraxonrasib

    Time frame: up to 21 weeks

    Tmax

  3. Area Under Blood Concentration Time Curve of Elironrasib and Daraxonrasib

    Time frame: up to 21 weeks

    AUC

  4. Elimination Half-Life of Elironrasib and Daraxonrasib

    Time frame: up to 21 weeks

    t1/2

  5. Ratio of accumulation of Elironrasib and Daraxonrasib from a single dose to steady state with repeated dosing

    Time frame: up to 21 weeks

    accumulation ratio

  6. Overall Response Rate (ORR) in Phase 1b

    Time frame: Up to approximately 3 years

    Overall response rate per RECIST v1.1

  7. Duration of Response (DOR)

    Time frame: Up to approximately 3 years

    Duration of response per RECIST v1.1

  8. Disease Control Rate in Phase 1b

    Time frame: Up to approximately 3 years

    Disease Control rate per RECIST v1.1

  9. Time to Response (TTR) in Phase 1b

    Time frame: Up to approximately 3 years

    Time to response per RECIST v1.1

  10. Progression-Free Survival (PFS)

    Time frame: Up to approximately 3 years

    Progression-free survival per RECIST v1.1

  11. Number of patients with AEs in Phase 2

    Time frame: Up to approximately 3 years

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

  12. Changes in vital signs in Phase 2

    Time frame: Up to approximately 3 years

    Number of patients with clinically significant changes in vital signs

  13. Changes in clinical laboratory values in Phase 2

    Time frame: Up to approximately 3 years

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

  14. Overall Survival (OS) in Phase 2

    Time frame: Up to approximately 3 years

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

Study contacts

Contact information is provided by the study sponsor or research team.

Revolution Medicines, Inc.

CONTACT

[email protected]

1-844-2-REVMED

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Registry information

Official study 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

Important dates

Study start
2023
Primary completion
2028
Study completion
2029
First posted
Nov 13, 2023
Registry last updated
Apr 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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