Study of RAS(ON) Inhibitors in Patients with Gastrointestinal Solid Tumors

Revolution Medicines

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: PDAC; Gastrointestinal Cancer; Metastatic Pancreatic Ductal Adenocarcinoma; Pancreatic Ductal Adenocarcinoma; CRC; Colorectal Cancer

Treatments: Drug: RMC-6236; Drug: nab-paclitaxel; Drug: bevacizumab; Drug: gemcitabine; Drug: cetuximab; Drug: mFOLFIRINOX regimen; Drug: mFOLFOX6 regimen

Study type: Interventional

Funder types: Industry

Identifiers

NCT06445062

RMC-GI-102

Details and patient eligibility

About

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

The first three subprotocols include the following:

Subprotocol A: RMC-6236 + 5-fluorouracil-based regimens

Subprotocol B: RMC-6236 + cetuximab with or without mFOLFOX6

Subprotocol C: RMC-6236 + gemcitabine + nab-paclitaxel

Full description

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

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

Subprotocol A is an open-label, multicenter study of RMC-6236 in combination with 5-fluorouracil-based regimens in patients with treatment-naïve unresectable or metastatic colorectal cancer or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol B is an open-label, multicenter study of RMC-6236 in combination with cetuximab with or without mFOLFOX6 in patients with unresectable or metastatic colorectal cancer or patients with previously treated or treatment-naïve metastatic pancreatic ductal adenocarcinoma. Subprotocol C is an open-label, multicenter study of RMC-6236 in combination with gemcitabine and nab-paclitaxel in patients with treatment-naïve metastatic pancreatic ductal adenocarcinoma. Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Enrollment: 406 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

All Patients (unless otherwise noted):

• ≥ 18 years of age
• ECOG PS is 0 to 1
• Adequate organ function as outlined by the study
• Pathologically or cytologically documented pancreatic carcinoma or poorly differentiated pancreatic carcinoma with metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A, B, and C)

Exclusion criteria

All Patients:

• Primary central nervous system (CNS) tumors
• Impaired gastrointestinal (GI) function that may significantly alter the absorption of RMC drugs
• Major surgery within 28 days of first dose

Other inclusion/exclusion criteria may apply.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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406 participants in 3 patient groups

Subprotocol A: RAS-mutated unresectable or metastatic CRC or metastatic PDAC

Experimental group

Description:

RMC-6236 (QD) and Bevacizumab with 5-fluorouracil-based regimens

Treatment:

Drug: mFOLFOX6 regimen

Drug: mFOLFIRINOX regimen

Drug: bevacizumab

Drug: RMC-6236

Subprotocol B: RAS-mutated unresectable or metastatic CRC or metastatic PDAC

Experimental group

Description:

RMC-6236 (QD) and Cetuximab with or without mFOLFOX6

Treatment:

Drug: mFOLFOX6 regimen

Drug: cetuximab

Drug: RMC-6236

Subprotocol C: metastatic PDAC

Experimental group

Description:

RMC-6236 (QD) and Gemcitabine with Nab-paclitaxel

Treatment:

Drug: gemcitabine

Drug: nab-paclitaxel

Drug: RMC-6236