Brief 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

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

616

participants targeted

Target at P75+ for phase_1

Timeline

31mo left

Started Jan 2024

Longer than P75 for phase_1

Geographic Reach

11 countries

89 active sites

Status

recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.9 years study duration

Study Progress47%

Jan 2024Dec 2028

First Submitted

Initial submission to the registry

November 30, 2023

Completed

8 days until next milestone

First Posted

Study publicly available on registry

December 8, 2023

Completed

1 month until next milestone

Study Start

First participant enrolled

January 18, 2024

Completed

3.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2027

Expected

1.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2028

Last Updated

March 9, 2026

Status Verified

June 1, 2025

Enrollment Period

3.4 years

First QC Date

November 30, 2023

Last Update Submit

March 5, 2026

Conditions

KRAS, NRAS, HRAS-mutated NSCLC RAS G12D-mutated NSCLC Non-Small Cell Lung Cancer, NSCLC KRAS G12C-mutated Solid Tumors, Lung Cancer Lung Cancer Stage IV, Advanced Solid Tumor, Cancer

Keywords

NSCLCKRAS G12CRAS MutationKRAS G12XNon-Small Cell Lung CancerLung CancerLung Cancer Stage IVAdvanced Solid TumorCancerRAS G12D

Outcome Measures

Primary Outcomes (2)

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
Dose limiting toxicities
Number of participants with dose limiting toxicities
21 days

Secondary Outcomes (6)

Drug concentrations over time
Up to 21 weeks
Cmax
Up to 21 weeks
Tmax
Up to 21 weeks
AUC
Up to 21 weeks
ORR
Up to 5 years
+1 more secondary outcomes

Study Arms (4)

Subprotocol A: KRAS G12C-Mutated Solid Tumors

EXPERIMENTAL

RMC-6291 (BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)

Drug: RMC-6291Drug: RMC-6236Drug: PembrolizumabDrug: CisplatinDrug: CarboplatinDrug: Pemetrexed

Subprotocol B: RAS-mutated NSCLC

EXPERIMENTAL

RMC-6236 (QD) and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W)

Drug: RMC-6236Drug: PembrolizumabDrug: CisplatinDrug: CarboplatinDrug: Pemetrexed

Subprotocol C: RAS G12D-mutated NSCLC

EXPERIMENTAL

RMC-9805 (QD or BID), RMC-6236 (QD), and Pembrolizumab (Q3W) with or without Chemotherapy (Q3W).

Drug: RMC-6236Drug: PembrolizumabDrug: CisplatinDrug: CarboplatinDrug: PemetrexedDrug: RMC-9805

Subprotocol D: RAS G12D-mutated NSCLC

EXPERIMENTAL

RMC-9805 (QD)

Drug: RMC-9805

Interventions

RMC-6291DRUG

Oral tablet

Subprotocol A: KRAS G12C-Mutated Solid Tumors

RMC-6236DRUG

Oral tablet