RMC-5127 for Solid Tumors

Overseen By Revolution Medicines Study Director

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Revolution Medicines, Inc.

Must not be taking: KRAS inhibitors

Disqualifiers: Primary CNS tumors, Major surgery, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

574 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new drug, RMC-5127 (an experimental treatment), to determine its safety and effectiveness for people with KRAS G12V-mutant solid tumors. Researchers aim to understand how well the drug works alone and in combination with other treatments like daraxonrasib or cetuximab. It suits adults with advanced cancer that hasn't responded to previous treatments and who can take pills. The goal is to see if these treatments can slow or stop the growth of these specific tumors. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new drug.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that RMC-5127 was safe in early animal studies for certain types of cancer. These tests indicated that the treatment was well-tolerated, meaning it didn't cause serious side effects. Although specific data on RMC-5127's effects in humans is not yet available, the early results are encouraging.

For the combination of RMC-5127 with cetuximab, clear data is not available. However, cetuximab is an approved cancer drug with well-known safety, suggesting it might be safe when used with RMC-5127.

Regarding the combination of RMC-5127 and daraxonrasib, early data from another trial showed that daraxonrasib, when used with other treatments for solid tumors, had manageable side effects that could be controlled.

Since the trial for RMC-5127 is in the early stages, the main goal is to study its safety in humans. Researchers are closely monitoring participants' reactions to the treatment and are vigilant for any side effects. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

RMC-5127 is unique because it targets solid tumors with a distinct mechanism of action. Unlike traditional treatments that often rely on chemotherapy to kill rapidly dividing cells, RMC-5127 works by specifically interfering with the signaling pathways that tumors need to grow. This precision makes it potentially more effective and less harmful to healthy cells. Researchers are excited about the combination treatments, such as RMC-5127 with Cetuximab and Daraxonrasib, as these combinations might enhance the treatment's effectiveness by attacking the cancer from multiple angles, offering hope for improved outcomes in challenging cases.

What evidence suggests that this trial's treatments could be effective for KRAS G12V-mutant solid tumors?

This trial will evaluate RMC-5127 in different treatment arms. Studies have shown promising results for RMC-5127 in treating certain tumors with the KRAS G12V mutation. Participants may receive RMC-5127 as monotherapy, which previously demonstrated an average survival of up to 15.6 months. Another arm will test RMC-5127 combined with cetuximab; previous studies reported that 89% of patients experienced good disease control. Additionally, RMC-5127 combined with daraxonrasib, tested in another arm, showed strong and lasting effects against tumors. These findings suggest that RMC-5127, whether used alone or with other treatments, could effectively treat these specific tumors. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 with advanced or metastatic solid tumors that have a specific mutation (KRAS G12V). Participants must have tried standard treatments without success or could not tolerate them. They should be relatively healthy, able to perform daily activities with ease or only limited help, and capable of taking oral medications.

Inclusion Criteria

My cancer can be measured by standard imaging tests.

My cancer has worsened or I couldn't tolerate the standard treatments.

I am fully active or restricted in physically strenuous activity but can do light work.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Dose Escalation

Participants receive escalating doses of RMC-5127 as monotherapy or in combination with daraxonrasib or cetuximab to determine the maximum tolerated dose

Up to 28 days

Dose Expansion

Participants receive the determined dose of RMC-5127 as monotherapy or in combination to further evaluate safety and efficacy

Up to Cycle 5 Day 1 (each cycle is up to 28 days)

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to approximately 3 years

What Are the Treatments Tested in This Trial?

Interventions

• RMC-5127

Trial Overview

The study is testing RMC-5127 alone and in combination with daraxonrasib or cetuximab. It aims to assess the safety, how well the body handles these drugs (pharmacokinetics), and their initial effectiveness against tumors with the KRAS G12V mutation.

How Is the Trial Designed?

Group I: Arm C: RMC-5127 + Cetuximab Combination Experimental Treatment 2 Interventions

Dose Escalation and Dose Expansion

Group II: Arm B: RMC-5127 + Daraxonrasib Combination Experimental Treatment 2 Interventions

Dose Escalation and Dose Expansion

Group III: Arm A: RMC-5127 Monotherapy Experimental Treatment 1 Intervention

Dose Escalation and Dose Expansion

Who Is Running the Clinical Trial?

Revolution Medicines, Inc.

Lead Sponsor

Trials

14

Recruited

4,500+

Citations

1.

clinicaltrials.gov

clinicaltrials.gov/study/NCT07349537?rank=1

Study of RMC-5127 in Patients With Advanced KRAS ...

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of RMC-5127 as a monotherapy and in ...

2.

ir.revmed.com

ir.revmed.com/static-files/6cc16295-a14a-4252-94ed-0980075ec420

On Target to Outsmart Cancer

Solid tumors. Monotherapy. + SOC, RAS(ON) inhibitor doublets or other investigational agents. RMC-5127 (G12V) is in preclinical development.

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC12658183/

KRAS-targeted therapies in colorectal cancer - PMC - NIH

The approval was granted for use in combination with cetuximab ... Automated real-world data integration improves cancer outcome prediction.

4.

ajmc.com

ajmc.com/view/addressing-kras-resistance-ras-on-therapies-find-limelight-at-aacr

Addressing KRAS Resistance, RAS(ON) Therapies Find ...

Median time to onset of initial response was 1.4 months (range, 1.2-2.8) and the disease control rate was 89% (95% CI, 65%-99%). Among patients ...

5.

cell.com

cell.com/cancer-cell/pdf/S1535-6108(24)00056-4.pdf

Exploiting the therapeutic implications of KRAS inhibition ...

All trials recruited patients harboring KRAS-G12C mutations, except trial with the multi-RAS inhibitor RMC-6236 which evaluated RAS-mutated.

6.

researchgate.net

researchgate.net/publication/384737272_Development_and_safety_of_investigational_and_approved_drugs_targeting_the_RAS_function_regulation_in_RAS_mutant_cancers

Development and safety of investigational and approved ...

This review centers on the evolution of RAS inhibitors in cancer therapy, delving into the common adverse effects associated with these inhibitors, their ...

7.

hematologyandoncology.net

hematologyandoncology.net/archives/march-2025-and-april-2025/targeting-ras-in-gastrointestinal-malignancies/

Targeting RAS in Gastrointestinal Malignancies

Updated data from the phase 1/2 LOXO-RAS-20001 trial demonstrated its efficacy and safety in 184 patients, including 83 with NSCLC, 32 with CRC, 24 with PDAC, ...