What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC), including targeted therapies like KRAS G12C inhibitors, often have side effects such as fatigue, nausea, and increased liver function tests. Other targeted therapies, such as gefitinib and erlotinib, are associated with mild and reversible skin and gastrointestinal disorders. Additionally, treatments like ramucirumab can increase the risk of bleeding, hypertension, and, rarely, intestinal perforation and arterial thrombosis. Overall, while these treatments can be effective, they come with a range of potential adverse events that need to be managed.

What prior FDA approvals exist?

For the treatment of Non-Small Cell Lung Cancer (NSCLC) with KRAS G12C mutations, the FDA has approved sotorasib and adagrasib. These drugs specifically target the KRAS G12C mutation, similar to the investigational drug RMC-6291. Additionally, for other genetic alterations in NSCLC, the FDA has approved targeted therapies such as selpercatinib and pralsetinib for RET fusion-positive NSCLC, and fam-trastuzumab deruxtecan for HER2 mutations. These approvals highlight the ongoing advancements in personalized, genotype-directed therapies for NSCLC.

What other types of research exist?

Promising novel alternatives to RMC-6291 for NSCLC patients include ARS-1620, which has shown improved effectiveness in KRAS-G12C mutant lung cancer cells and mouse models, and the MEK inhibitor selumetinib, which is currently in a phase III trial for KRAS mutant NSCLC. Additionally, everolimus has shown activity in patients with KRAS G12F-mutated tumors and warrants further investigation.

← Back to Search

KRAS G12C(ON) inhibitor

RMC-6291 for Solid Cancers

Phase 1

Waitlist Available

Research Sponsored by Revolution Medicines, Inc.

Eligibility Criteria Checklist

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

Must have

Subject must be ≥18 years of age.

Prior treatment with a KRASG12C (OFF) inhibitor allowed for dose escalation

Must not have

Major surgical procedures within 28 days or non-study-related minor procedures within 7 days of treatment.

Prior therapy with KRASG12C (ON) inhibitor

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 3 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests a new drug, RMC-6291, in adults with advanced cancers that have a specific mutation. The drug aims to block a faulty protein in these cancer cells to stop their growth.

Who is the study for?

Adults over 18 with advanced solid tumors that have a specific mutation (KRASG12C) can join. They should have tried standard treatments, be in fairly good health, and able to do daily activities. Not for those who've had recent surgery or brain tumors/metastases.

What is being tested?

The trial is testing RMC-6291, a new drug targeting the KRAS G12C mutation in cancer cells. It's given alone to find the safest high dose and best dose for Phase 2 trials based on how patients react and what levels of the drug appear in their blood.

What are the potential side effects?

Possible side effects include issues related to organ inflammation, reactions at the infusion site, tiredness, stomach problems like nausea or diarrhea, changes in blood counts leading to increased infection risk or bleeding.

Eligibility Criteria

Inclusion Criteria

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

Select...

I am 18 years old or older.

Select...

I have been treated with a KRASG12C inhibitor before.

Select...

I am fully active or can carry out light work.

Exclusion Criteria

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

Select...

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

Select...

I have been treated with a KRASG12C inhibitor before.

Select...

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

Select...

My cancer originated in the brain or spinal cord.

Select...

I have active cancer spread to my brain.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 3 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~3 years

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

Treatment Details

Study Objectives

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

Primary study objectives

Adverse events

Dose Limiting Toxicities

Secondary study objectives

Area Under Blood Concentration Time Curve of RMC-6291

Disease Control Rate (DCR)

Duration of Response (DOR)

+7 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: RMC-6291Experimental Treatment1 Intervention

Dose Escalation and Dose Expansion

0 / 8Eligibility 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 sotorasib and adagrasib, specifically inhibit the KRAS G12C mutation by locking the KRAS protein in its inactive state, thereby preventing cancer cell proliferation. This is particularly relevant for patients with KRAS G12C mutations, as these therapies offer a more personalized and effective treatment option compared to traditional chemotherapy. Immunotherapies, like pembrolizumab, enhance the immune system's ability to recognize and destroy cancer cells by targeting PD-1/PD-L1 pathways. Chemotherapy, using drugs like cisplatin and paclitaxel, works by killing rapidly dividing cells but lacks the specificity of targeted treatments. Understanding these mechanisms helps in selecting the most appropriate and effective treatment for NSCLC patients based on their specific genetic mutations and overall health condition.

Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation.