What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include RAS inhibitors, chemotherapy, immunotherapy, and targeted therapies for specific mutations. RAS inhibitors, like RMC-6236, often cause fatigue, nausea, diarrhea, and increased liver function tests. Chemotherapy side effects typically include neutropenia, anemia, fatigue, nausea, vomiting, and hair loss. Immunotherapy can lead to immune-related adverse events such as rash, colitis, pneumonitis, and endocrinopathies. Targeted therapies for specific mutations may have unique side effects; for example, EGFR inhibitors can cause rash and diarrhea, while ALK inhibitors may lead to gastrointestinal disturbances and liver enzyme elevations.

What prior FDA approvals exist?

For Non-Small Cell Lung Cancer (NSCLC), the FDA has approved several targeted therapies focusing on specific genetic mutations. Sotorasib and adagrasib are notable for targeting the KRAS G12C mutation, a common alteration in NSCLC. Sotorasib was the first approved agent for KRAS G12C-mutated NSCLC, showing a median progression-free survival (PFS) of 6.3 months. Adagrasib, another KRAS G12C inhibitor, demonstrated a median PFS of 6.5 months and an overall survival of 12.6 months in clinical trials. These treatments are similar to the investigational RAS inhibitor RMC-6236, which is being studied for its efficacy in advanced solid tumors with specific RAS mutations.

What other types of research exist?

Promising novel alternatives to RMC-6236 for NSCLC patients include second-generation ALK inhibitors like alectinib and ceritinib, CDK4/6 inhibitors, and NTRK inhibitors such as entrectinib and larotrectinib. These therapies have shown efficacy in clinical trials and are potential options for treatment in 2024.

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Small Molecule Inhibitor

RMC-6236 for Cancer

Phase 1

Recruiting

Research Sponsored by Revolution Medicines, Inc.

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed advanced solid tumor with specific KRAS G12 mutations (dose escalation) or RAS mutations (dose optimization/expansion) identified through deoxyribonucleic acid (DNA) sequencing

Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Must not have

Known or suspected impairment of gastrointestinal function that may prohibit ability to swallow or absorb an oral medication

Primary central nervous system (CNS) tumors

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2.5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called RMC-6236, which is taken by mouth and targets a protein called RAS. It is aimed at adults with advanced cancers that have specific mutations in the RAS protein. The drug works by blocking this protein, which helps stop the cancer cells from growing.

Who is the study for?

This trial is for adults with advanced solid tumors that have specific RAS mutations, who've already tried standard treatments. They need to be relatively healthy and active (ECOG status of 0 or 1), with good organ function. It's not for those with primary brain tumors, untreated brain metastases, issues absorbing oral meds, or other serious health problems.

What is being tested?

The study tests the safety and how well people tolerate RMC-6236, a new medication aimed at treating various types of cancer like lung and colorectal cancer that have certain genetic changes known as RAS mutations.

What are the potential side effects?

While the side effects of RMC-6236 are being studied in this trial and aren't fully known yet, they may include typical reactions to cancer medications such as nausea, fatigue, liver issues, skin reactions and potential allergic responses.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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My advanced cancer has specific KRAS G12 or RAS mutations.

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

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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I have issues with my digestive system that might affect my ability to take pills.

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My cancer originated in the brain or spinal cord.

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I have brain metastases that haven't been treated.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2.5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2.5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2.5 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Overall Response Rate (ORR)

+2 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Experimental: RMC-6236Experimental Treatment1 Intervention

Enrollment into dose exploration may be from any advanced solid tumor type with KRAS p.G12 mutations. Enrollment into dose expansion/optimization may be from groups consisting of patients with a single histotype/genotype (for example, KRAS G12-mutated NSCLC, PDAC, CRC, RAS mutant NSCLC, Melanoma, gynecological cancer or other solid tumors not previously specified). RAS mutant is defined as any nonsynonymous mutation of KRAS, NRAS, or HRAS at codons 12, 13, or 61 (G12, G13, or Q61)

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) include targeted therapies, immunotherapies, and chemotherapy. Targeted therapies, such as EGFR inhibitors (e.g., osimertinib) and ALK inhibitors (e.g., crizotinib), work by specifically targeting genetic mutations that drive cancer growth, leading to more effective and personalized treatment. Immunotherapies, like pembrolizumab, enhance the body's immune response against cancer cells by targeting PD-1/PD-L1 pathways. Chemotherapy, using agents like pemetrexed and carboplatin, kills rapidly dividing cancer cells but can also affect normal cells. For patients with specific mutations like KRAS, emerging treatments such as RAS inhibitors (e.g., RMC-6236) are being studied to directly inhibit the RAS pathway, which is crucial for cancer cell proliferation and survival. Understanding these mechanisms allows for more precise and effective treatment strategies, improving outcomes and reducing side effects for NSCLC patients.