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NCT Number: NCT05462717

Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating doses of RMC-6291 (KRAS G12C(ON) inhibitor) monotherapy in adult subjects with advanced solid tumors and to identify the maximum tolerated dose (MTD), and the recommended Phase 2 dose.

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This study is active but is not currently recruiting participants.

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Key information

Conditions

Non-small Cell Lung Cancer (NSCLC) Adenocarcinoma Adnexal Diseases Advanced Solid Tumor 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 (CRC) 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

Primary location

Southside Cancer Care Centre, Sydney, New South Wales, Australia

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About this study

This is an open-label, multicenter, Phase 1/1b study of RMC-6291 monotherapy in subjects with advanced KRASG12C-mutant solid tumors. The study will include 2 components: a Dose-Escalation and a Dose-Expansion. Subjects will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Subject must be ≥18 years of age.
  • Subject must have pathologically documented, locally advanced or metastatic KRASG12C-mutated solid tumor malignancy (not amenable to curative surgery) that has previously been treated with standard-of-care therapies for respective tumor types, is intolerant to, or is considered ineligible for standard-of-care anticancer treatments.
  • ECOG performance status 0 or 1
  • Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation and for NSCLC in dose expansion
  • 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.
  • Prior therapy with KRASG12C (ON) inhibitor

Other inclusion/exclusion criteria may apply.

Treatment and study plan

RMC-6291

Drug

Oral tablet once or twice a day

Primary outcomes

  1. Adverse events

    Time frame: up to 3 years

    Number of participants with adverse events

  2. Dose Limiting Toxicities

    Time frame: The first 21 days (i.e. Cycle 1)

    Number of participants with dose limiting toxicities

Secondary outcomes

  1. Maximum Observed Blood Concentration of RMC-6291

    Time frame: 7 Cycles

    Cmax

  2. Time to Reach Maximum Blood Concentration of RMC-6291

    Time frame: 7 Cycles

    Tmax

  3. Area Under Blood Concentration Time Curve of RMC-6291

    Time frame: 7 Cycles

    AUC

  4. Elimination Half-Life of RMC-6291

    Time frame: 7 Cycles

    t1/2

  5. Ratio of accumulation of RMC-6291 from a single dose to steady state with repeated dosing

    Time frame: 7 Cycles

    accumulation ratio

  6. Overall Response Rate (ORR)

    Time frame: 3 years

    Overall response rate per RECIST v1.1

  7. Duration of Response (DOR)

    Time frame: 3 years

    Duration of response per RECIST v1.1

  8. Disease Control Rate (DCR)

    Time frame: 3 years

    Disease control rate per RECIST v1.1

  9. Time to Response (TTR)

    Time frame: 3 years

    Time to response per RECIST v1.1

  10. Progression-Free Survival (PFS)

    Time frame: 3 years

    Progression-free survival per RECIST v1.1

Sponsors and collaborators

Lead sponsor

Revolution Medicines, Inc.

Industry

Registry information

Official study title

Phase 1/1b, Multicenter, Open-Label, Dose Escalation and Dose Expansion Study of RMC-6291 Monotherapy in Subjects With Advanced KRASG12C Mutant Solid Tumors

Important dates

Study start
2022
Primary completion
2027
Study completion
2027
First posted
Jul 18, 2022
Registry last updated
May 15, 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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