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

Non-Small Cell Lung Cancer, NSCLC Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06162221
• Other study ID #: RMC-LUNG-101
• Status: Recruiting
• Phase: Phase 1/Phase 2
• Start date: January 18, 2024
• Est. completion date: December 2028

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 each other. The first two subprotocols include the following: Subprotocol A: RMC-6291 + SOC Subprotocol B: RMC-6236 + SOC

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 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), 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 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) Each subprotocol consists of two parts: Part 1 - Dose Exploration and Part 2 - Dose Expansion.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 352
• Est. completion date: December 2028
• Est. primary completion date: June 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
• 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) 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 < 28 days of first dose
• Active or history of interstitial lung disease (ILD) or pneumonitis requiring steroids Other inclusion/exclusion criteria may apply.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Neoplasms
• Non-Small Cell Lung Cancer, NSCLC

Intervention

Drug:
• RMC-6291
Oral tablet
• RMC-6236
Oral tablet
• Pembrolizumab
IV Infusion
• Cisplatin
IV Infusion
• Carboplatin
IV Infusion
• Pemetrexed
IV infusion

Locations

Country	Name	City	State
United States	NEXT Oncology Virginia	Fairfax	Virginia
United States	MD Anderson Cancer Center	Houston	Texas
United States	NEXT Oncology Dallas	Irving	Texas
United States	Boca Raton Clinical Research Associates	Plantation	Florida
United States	Clinical Research Alliance	Westbury	New York

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	Incidence and severity of treatment-emergent Adverse Events (AEs) and serious AEs and clinically significant changes in laboratory values, ECGs and vital signs	Up to 5 years
Primary	Dose limiting toxicities	Number of participants with dose limiting toxicities	21 days
Secondary	Cmax	Maximum observed blood concentration of each drug per subprotocol	Up to 21 weeks
Secondary	Tmax	Time to reach maximum blood concentration of each drug per subprotocol	Up to 21 weeks
Secondary	AUC	Area under the concentration-time curve of each drug per subprotocol	Up to 21 weeks
Secondary	ORR	Overall Response Rate per RECIST v1.1	Up to 5 years
Secondary	DOR	Duration of Response per RECIST v1.1	Up to 5 years