Menu
Recruiting NCT06040541

Study of RMC-9805 in Participants With KRAS G12D-Mutant Solid Tumors

Phase I Interventional Non-small Cell Lung Cancer (NSCLC) Colorectal Cancer (CRC) Pancreatic Ductal Adenocarcinoma (PDAC) Advanced Solid Tumors

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: RMC-9805, RMC-6236.
Who it may be relevant to
Registry conditions: Non-small Cell Lung Cancer (NSCLC), Colorectal Cancer (CRC), Pancreatic Ductal Adenocarcinoma (PDAC), Advanced Solid Tumors. 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
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
Official title

Phase 1/1b, Multicenter, Open-Label, Study of RMC 9805 in Participants With Advanced KRASG 12D-Mutant Solid Tumors

Overview

This study is to evaluate the safety and tolerability of RMC-9805 as monotherapy and in combination with RMC-6236 in adults with KRAS G12D-mutant solid tumors.

Detailed description

This is an open-label, multicenter, Phase 1/1b study of RMC-9805, a selective and orally bioavailable KRAS G12D(ON) inhibitor, in subjects with KRASG12D-mutant solid tumors to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity. The study consists of two arms: RMC-9805 monotherapy arm and RMC-9805 plus RMC-6236 combination arm. Both arms consist of two parts: Part 1- dose exploration and Part 2- dose expansion.

Interventions

  • Drug RMC-9805
    Oral Tablets
  • Drug RMC-6236
    Oral Tablets

Primary outcome measures

  • Adverse events [Time frame: Up to 3 years]
  • Dose Limiting Toxicities [Time frame: 21 days]
Secondary outcome measures (10)
  • Maximum Observed Blood Concentration (Cmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Cmax of RMC-6236 in combination with RMC-9805 [Time frame: up to 21 weeks]
  • Time to Reach Maximum Blood Concentration (Tmax) of RMC-9805 as monotherapy and in combination with RMC-6236, and Tmax of RMC-6236 in combination with RMC-9805 [Time frame: up to 21 weeks]
  • Area Under Blood Concentration Time Curve (AUC) of RMC-9805 as monotherapy and in combination with RMC-6236, and AUC of RMC-6236 in combination with RMC-9805 [Time frame: up to 21 weeks]
  • Ratio of accumulation of RMC-9805 from a single dose to steady state with repeated dosing as monotherapy and in combination with RMC-6236, and ratio of accumulation of RMC-6236 in combination with RMC-9805 [Time frame: up to 21 weeks]
  • Elimination Half-Life (t1/2) of RMC-9805 as monotherapy and in combination with RMC-6236, and t1/2 of RMC-6236 in combination with RMC-9805 [Time frame: up to 21 weeks]
  • Overall Response Rate (ORR) [Time frame: up to 3 years]
  • Duration of Response (DOR) [Time frame: up to 3 years]
  • Disease Control Rate (DCR) [Time frame: up to 3 years]
  • Time to Response (TTR) [Time frame: up to 3 years]
  • Progression-Free Survival (PFS) [Time frame: up to 3 years]

Eligibility criteria

Inclusion criteria

  • Pathologically documented, locally advanced or metastatic solid tumor with a KRAS G12D-mutation
  • Received and progressed or been intolerant to prior standard therapy (including targeted therapy) appropriate for tumor type and stage
  • ECOG performance status 0 or 1
  • Adequate organ function

Exclusion criteria

  • Primary central nervous system (CNS) tumors
  • Known or suspected leptomeningeal or active brain metastases or spinal cord compression
  • Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication
  • Participant was previously treated with an investigational KRAS G12D inhibitor, pan- or multi-RAS inhibitor, or had prior therapy with any direct RAS-targeted therapy (eg, degraders and inhibitors)

Other inclusion/exclusion criteria may apply.

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
Parallel assignment
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 17 centers
  • University of California, Davis Comprehensive Cancer Center — Sacramento
  • Smilow Cancer Hospital (Yale University) — New Haven
  • Florida Cancer Specialists — Sarasota
  • Lee Moffitt Cancer Center — Tampa
  • Johns Hopkins University — Baltimore
  • Massachusetts General Hospital — Boston
  • Dana-Farber Cancer Institute — Boston
  • NYU Langone — New York
  • … and 9 more centers

Publications

  • Weller C, Burnett GL, Jiang L, Chakraborty S, Zhang D, Vita NA, Dilly J, Kim E, Maldonato B, Seamon K, Eilerts DF, Milin A, Marquez A, Spradlin J, Helland C, Gould A, Ziv TB, Dinh P, Steele SL, Wang Z, Mu Y, Chugh S, Feng H, Hennessey C, Wang J, Roth J, Rees M, Ronan M, Wolpin BM, Hahn WC, Holderfield M, Wang Z, Koltun ES, Singh M, Gill AL, Smith JAM, Aguirre AJ, Jiang J, Knox JE, Wildes D. A neom PMID 40705880
  • 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: NCT06040541 · RMC-9805-001

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗