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

Colorectal Cancer Clinical Trial

Official title:

A Platform Study of RAS(ON) Inhibitors in Patients With Gastrointestinal Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06445062
• Other study ID #: RMC-GI-102
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: May 24, 2024
• Est. completion date: July 15, 2027

Study information

• Verified date: May 2024
• Source: Revolution Medicines, Inc.
• Contact: Revolution Medicines
• Phone: 650-779-2300
• Email: CT-inquiries[@]RevMed.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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 unresectable or metastatic colorectal cancer or 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 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 metastatic pancreatic ductal adenocarcinoma. Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 406
• Est. completion date: July 15, 2027
• Est. primary completion date: May 15, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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
• Must have pathologically documented, pancreatic carcinoma with documented metastatic disease or RAS-mutated, histologically or cytologically confirmed colorectal adenocarcinoma with documented unresectable or metastatic disease (Subprotocol A and B)
• Must have pathologically documented, poorly differentiated pancreatic carcinoma with documented metastatic disease (Subprotocol 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.

Related Conditions & MeSH terms

• Adenocarcinoma
• Colorectal Cancer
• Colorectal Neoplasms
• CRC
• Gastrointestinal Cancer
• Gastrointestinal Neoplasms
• Metastatic Pancreatic Ductal Adenocarcinoma
• Pancreatic Ductal Adenocarcinoma
• PDAC

Intervention

Drug:
• RMC-6236
Oral tablet
• mFOLFOX6 regimen
IV infusion
• bevacizumab
IV infusion
• mFOLFIRINOX regimen
IV infusion
• cetuximab
IV infusion
• gemcitabine
IV infusion
• nab-paclitaxel
IV infusion

Locations

Country	Name	City	State
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	NEXT Oncology Dallas	Irving	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Revolution Medicines, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse events	Evaluate the safety and tolerability in the study population characterized by incidence, abnormal laboratory assessments, severity, and seriousness of adverse events in relation to the study treatment.	Up to 3 years
Primary	Dose limiting toxicities	Number of participants with dose limiting toxicities	28 days
Secondary	Pharmacokinetics of RMC-6236	Blood concentration of RMC-6236 over time	21 weeks
Secondary	ORR	Overall Response Rate per RECIST v1.1	Up to 3 years
Secondary	DOR	Duration of Response per RECIST v1.1	Up to 3 years
Secondary	DCR	Incidence of Response per RECIST v1.1	Up to 3 years
Secondary	TTR	Time to Response per RECIST v1.1	Up to 3 years
Secondary	PFS	Progression Free Survival per RECIST v1.1	Up to 3 years
Secondary	OS	Overall Survival	Up to 3 years