RMC-6291 + RMC-6236 for Advanced Solid Cancers

Recruiting at 59 trial locations

Overseen By Revolution Medicines, Inc.

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Revolution Medicines, Inc.

Disqualifiers: Primary CNS tumors, Active brain metastases, GI impairment, others

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

Compensation: Varies

Number of Visits: Unknown

210 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the safety and effects of two experimental treatments, RMC-6291 and RMC-6236, for individuals with advanced solid tumors carrying the KRAS G12C mutation. The researchers aim to determine the effectiveness of these treatments and how the body processes them. The trial includes participants with certain cancers, such as non-small cell lung cancer (NSCLC), who have previously tried other unsuccessful treatments. It may suit individuals with KRAS G12C-mutated tumors seeking alternative options after prior treatments. As a Phase 1 trial, this research explores how the treatment works in people, offering participants the chance to be among the first to receive these new treatments.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that RMC-6291 and RMC-6236 have promising safety results. Studies indicate that RMC-6291 is generally well-tolerated at different doses, with most patients not experiencing severe side effects.

RMC-6236 is undergoing testing in several trials and shows potential as a treatment. Although detailed safety data for using both together is still being collected, ongoing studies suggest that patients can tolerate both treatments.

As this trial is in the early testing phase, it primarily focuses on understanding safety and how the body processes the drugs. While safety information is still being developed, early signs are encouraging. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about RMC-6291 and RMC-6236 because they bring a fresh approach to treating advanced solid cancers. Unlike current treatments that often rely on chemotherapy or targeted therapies that inhibit specific proteins, these drugs are designed to target specific genetic mutations driving cancer growth, potentially offering more precision in treatment. RMC-6291 and RMC-6236 work by addressing the root causes of tumor development at a molecular level, which might lead to better outcomes with fewer side effects. This innovative approach aims to provide more effective and personalized cancer therapies, giving hope for improved survival rates and quality of life for patients with advanced cancers.

What evidence suggests that this trial's treatments could be effective for advanced solid cancers?

Research shows that both RMC-6291 and RMC-6236 could help treat solid tumors with the KRAS G12C mutation. This trial will administer a combination of RMC-6291 and RMC-6236 to participants. RMC-6291 has shown early signs of effectiveness in patients and is generally well-tolerated, suggesting it might effectively target these cancer cells. Similarly, RMC-6236 acts as a strong inhibitor by attaching to a specific protein to stop cancer growth. Earlier studies indicate that patients have tolerated these treatments well, with most maintaining their prescribed doses. While more research is needed, these findings offer hope that these treatments could be effective for people with this specific cancer mutation. ^{1 2 3 5 6}

Who Is on the Research Team?

Revolution Medicines, Inc.

Principal Investigator

Revolution Medicines, Inc.

Are You a Good Fit for This Trial?

This trial is for adults with advanced solid tumors that have a specific mutation (KRAS G12C). Participants must have tried other treatments like immunotherapy and chemotherapy. They should be in good physical condition, but can't join if they've had recent surgery or active brain metastases.

Inclusion Criteria

I have NSCLC and was treated with immunotherapy, chemotherapy, and KRAS G12C inhibitors.

I have solid tumors that were treated before.

My cancer is advanced, cannot be cured with surgery, and has a specific KRAS mutation.

Exclusion Criteria

My cancer originated in the brain or spinal cord.

I haven't had major surgery in the last 28 days or minor surgery in the last 7 days.

I have a digestive issue that affects how my body absorbs medicine.

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-6291 and RMC-6236 to identify the maximum tolerated dose

21 weeks

Dose Expansion

Participants receive the recommended Phase 2 dose to assess preliminary antitumor activity

21 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

3 years

What Are the Treatments Tested in This Trial?

Interventions

• RMC-6236
• RMC-6291

Trial Overview The study tests the combination of two drugs, RMC-6291 and RMC-6236, on patients with KRAS G12C-mutated tumors to assess safety, how well the body tolerates them, and how the body processes these drugs.

How Is the Trial Designed?

Group I: RMC-6291 and RMC-6236 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+

Published Research Related to This Trial

In a study of 93 colorectal cancer patients, RAS mutations were found in over half of the participants, but these mutations did not negatively impact the effectiveness of chemotherapy or the anti-VEGF drug bevacizumab, as there were no significant differences in progression-free survival (PFS) or overall survival (OS) between patients with RAS mutations and those without.

Interestingly, patients with RAS mutations showed a trend towards better PFS and OS when treated with bevacizumab, suggesting that RAS mutations do not predict a lack of benefit from anti-angiogenic therapy, and may even indicate a favorable response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of RAS mutation status as a prognostic factor for patients with advanced colorectal cancer treated with first-line chemotherapy based on fluoropyrimidines and oxaliplatin, with or without bevavizumab: A retrospective analysis. Garde Noguera, J., Jantus-Lewintre, E., Gil-Raga, M., et al.[2020]

Combining Trametinib (a MEK inhibitor) with Dasatinib (an SRC inhibitor) enhances cell death in colorectal cancer (CRC) cell lines, particularly in those classified as Consensus Molecular Subtype 4 (CMS4), which are known for their resistance to traditional therapies.

The study suggests that gene expression signature scores related to RAS pathway activation and MEK inhibitor resistance can help predict which CRC tumors are likely to respond to this dual-targeted therapy, potentially improving treatment outcomes for patients with resistant tumors.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ras Pathway Activation and MEKi Resistance Scores Predict the Efficiency of MEKi and SRCi Combination to Induce Apoptosis in Colorectal Cancer. Davis, TB., Gupta, S., Yang, M., et al.[2023]

Phase I trials of RMC-6236, a pan-RAS inhibitor, and HRS-4642, a KRASG12D inhibitor, have shown that both drugs are safe for use and exhibit promising antitumor activity.

These findings highlight the potential of developing RAS-targeted therapies beyond just KRASG12C, indicating a growing interest in more comprehensive treatment options for cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drugging RAS: Moving Beyond KRASG12C. [2023]

New drugs targeting the RAS pathway, such as KRASG12C inhibitors, have shown promising results in clinical trials for treating RAS-mutated metastatic colorectal cancer (mCRC), indicating potential for improved patient outcomes.

Recent insights into adaptive resistance and feedback loops in the RAS pathway have led to the development of strategic combination therapies, which may help overcome resistance issues and enhance treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Developments in Treating RAS-Mutated Metastatic Colorectal Cancer. Janssens, K., Lambrechts, C., Geerinckx, B., et al.[2023]

In a study using mouse models, tumors driven by the cooperation of two oncogenes (Myc and mutant Kras) were found to depend on the activity of just one of these oncogenes for their survival, indicating a potential target for therapy.

Deinducing either oncogene led to tumor regression, and simultaneous deinduction of both resulted in improved survival, suggesting that combination therapies targeting multiple oncogenes could enhance treatment efficacy and prevent relapse.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oncogene cooperation in tumor maintenance and tumor recurrence in mouse mammary tumors induced by Myc and mutant Kras. Podsypanina, K., Politi, K., Beverly, LJ., et al.[2021]

Citations

1. ir.revmed.com ir.revmed.com/news-releases/news-release-details/revolution-medicines-present-updated-elironrasib-safety-and

Revolution Medicines to Present Updated Elironrasib ... These results are from RMC-6291-001, an ongoing multicenter, Phase 1 trial designed to evaluate elironrasib (RMC‑6291) monotherapy in patients ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06128551

NCT06128551 | Study of RMC-6291 in Combination with ... This study is to evaluate the safety, tolerability, and PK profiles of RMC-6291 and RMC-6236 in adults with KRAS G12C-mutated solid tumors.

3. ir.revmed.com ir.revmed.com/news-releases/news-release-details/revolution-medicines-presents-encouraging-clinical-data-rmc-6236

Revolution Medicines Presents Encouraging Clinical Data ... RMC-6291 demonstrated preliminary evidence of clinical activity and an acceptable safety profile that was generally well tolerated across dose levels.

4. pubs.acs.org pubs.acs.org/doi/10.1021/acs.jmedchem.5c01441

Highlight on a Phase III Clinical Candidate Daraxonrasib ... Drug discovery and development of daraxonrasib (RMC-6236), a potent, noncovalent RAS(ON) molecular glue inhibitor in multiple clinical trials.

5. firstwordpharma.com firstwordpharma.com/story/5917927

Revolution Medicines Provides Clinical Updates from its ... The mean dose intensities for RMC-6291 and RMC-6236 were 95% and 92%, respectively. A subset of efficacy-evaluable patients with colorectal ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06162221

NCT06162221 | Study of RAS(ON) Inhibitors in Patients ... The purpose of this platform study is to evaluate the safety, tolerability, pharmacokinetics (PK), and preliminary antitumor activity of novel RAS(ON) ...