Study of RAS(ON) Inhibitors in Patients With Advanced RAS-mutated NSCLC

a study on Lung Cancer Non-Small Cell Lung Cancer Solid Tumor Neoplasms Lung Tumor

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at San Francisco, California and other locations
Dates
study started
study ends around
Principal Investigator
by Michael Cheng
Headshot of Michael Cheng
Michael Cheng

Description

Summary

The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors as a monotherapy or combined with Standard(s) of Care (SOC) or with each other.

The first four subprotocols include the following:

Subprotocol A: RMC-6291 +/- RMC-6236 + SOC Subprotocol B: RMC-6236 + SOC Subprotocol C: RMC-9805 +/- RMC-6236 + SOC Subprotocol D: RMC-9805

Official Title

A Platform Study of RAS(ON) Inhibitors in Patients With RAS-Mutated Non-Small Cell Lung Cancer (NSCLC)

Details

The platform study design allows combinations of RAS(ON) inhibitors with other anticancer agents or as a monotherapy to be evaluated in patients with RAS-mutated solid tumors with a focus on NSCLC.

This is an open-label platform Phase 1b/2 study to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) inhibitors combined with Standard of Care (SOC), or as a monotherapy and to define the Recommended Phase 2 Dose and Schedule (RP2DS). Enrollment of patients with KRAS or RAS mutations will be specified in each subprotocol.

Subprotocol A is an open-label, multicenter, Phase 1b/2 study of RMC-6291, with or without RMC-6236, in combination with pembrolizumab, with or without chemotherapy, in patients with KRAS G12C-mutated advanced solid tumors.

Subprotocol B is an open-label, multicenter, Phase1b/2 study of RMC-6236 in combination with pembrolizumab, with or without chemotherapy, in patients with RAS-mutated non-small cell lung cancer (NSCLC)

Subprotocol C is an open-label, multicenter, Phase1b/2 study of RMC-9805 with or without RMC-6236, in combination with other anticancer agents, in patients with RAS G12D-mutated non-small cell lung cancer (NSCLC)

Subprotocol D is a Phase 2, Open-label, Multicenter Study of Zoldonrasib (RMC-9805) in Previously Treated Patients with RAS G12D-Mutant Non-Small Cell Lung Cancer (NSCLC)

Subprotocols A, B, and C consist of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion. Subprotocol D consists of only one part.

Keywords

Non-Small Cell Lung Cancer, NSCLC, KRAS, NRAS, HRAS-mutated NSCLC, KRAS G12C-mutated Solid Tumors, Lung Cancer, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer, RAS G12D-mutated NSCLC, NSCLC, KRAS G12C, RAS Mutation, KRAS G12X, Non-Small Cell Lung Cancer, Lung Cancer, Lung Cancer Stage IV, Advanced Solid Tumor, Cancer, RAS G12D, Neoplasms, Lung Neoplasms, Non-Small-Cell Lung Carcinoma, Carboplatin, Pembrolizumab, Pemetrexed, RMC-6291, RMC-6236, Cisplatin, RMC-9805, KRAS G12C-Mutated Solid Tumors, RAS-mutated NSCLC

Eligibility

You can join if…

Open to people ages 18 years and up

All Patients (unless otherwise noted):

  • ≥ 18 years of age
  • ECOG PS is 0 to 1
  • Adequate organ function as outlined by the study
  • Received prior standard therapy appropriate for tumor type and stage
  • Must have pathologically documented, locally advanced or metastatic KRAS G12C-mutated solid tumor malignancy (not amenable to curative surgery) (Subprotocol A)
  • Must have pathologically documented, locally advanced or metastatic RAS-mutated NSCLC (Subprotocol B)
  • Must have pathologically documented, locally advanced or metastatic RAS G12D-mutated NSCLC (Subprotocol C and Subprotocol D)

You CAN'T join if...

All Patients:

  • Primary central nervous system (CNS) tumors
  • Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
  • Major surgery < 28 days of first dose
  • Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids

Other inclusion/exclusion criteria may apply.

Locations

  • UCSF Medical Center - Mission Bay accepting new patients
    San Francisco California 94158 United States
  • Stanford University - Stanford Cancer Institute accepting new patients
    Stanford California 94305 United States

Lead Scientist at UCSF

  • Michael Cheng
    Dr. Michael L. Cheng is an academic medical oncologist and Assistant Professor at the University of California, San Francisco (UCSF), where he leads clinical and translational research focused on advancing discoveries in cancer genomics and developing improved therapies for thoracic malignancies, especially Non-Small Cell Lung Cancer (NSCLC). Dr. Cheng received his M.D.

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Revolution Medicines, Inc.
ID
NCT06162221
Phase
Phase 1/2 research study
Study Type
Interventional
Participants
Expecting 616 study participants
Last Updated
Contact us about this trial