What is the mechanism of action of this treatment?

The most common treatments for Non-Small Cell Lung Cancer (NSCLC) often involve targeted therapies that inhibit specific molecular pathways critical for cancer cell survival and proliferation. Avutometinib (VS-6766) is a dual RAF/MEK inhibitor that targets the RAF/MEK/ERK signaling pathway, which is frequently activated in NSCLC due to mutations in genes like KRAS and BRAF. By inhibiting both RAF and MEK, Avutometinib can more effectively block this pathway, potentially reducing tumor growth and overcoming resistance mechanisms that limit the efficacy of single-agent therapies. This is crucial for NSCLC patients as it offers a more tailored and potentially more effective treatment option, especially for those with specific genetic mutations driving their cancer.

What side effects are associated with this type of intervention?

Common treatments for Non-Small Cell Lung Cancer (NSCLC) include chemotherapy, antiangiogenic therapy, EGFR inhibitors, ALK inhibitors, and RAF/MEK inhibitors like Avutometinib (VS-6766). Chemotherapy often causes nausea, fatigue, and neutropenia. Antiangiogenic therapies can lead to hypertension, bleeding, and thromboembolic events. EGFR inhibitors frequently cause rash and diarrhea, while ALK inhibitors may result in gastrointestinal disturbances and liver enzyme abnormalities. RAF/MEK inhibitors, such as Avutometinib, can cause skin rash, diarrhea, and elevated liver enzymes. These side effects vary in severity and frequency among patients.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for the treatment of Non-Small Cell Lung Cancer (NSCLC) with specific genetic mutations. For instance, dabrafenib in combination with trametinib, both of which target the BRAF V600E mutation, has shown significant efficacy in NSCLC. Other targeted therapies include EGFR inhibitors like osimertinib, erlotinib, and gefitinib for EGFR-mutant NSCLC, and ALK inhibitors such as crizotinib and alectinib for ALK-positive NSCLC. These approvals highlight the trend towards personalized, genotype-directed therapy in NSCLC, similar to the approach being studied with Avutometinib (VS-6766).

What other types of research exist?

Promising alternatives to Avutometinib (VS-6766) for NSCLC patients include: 1) Larotrectinib and Entrectinib for patients with NTRK gene fusions, both of which have shown high response rates in clinical trials. 2) Selpercatinib and Pralsetinib for patients with RET mutations, which are suggested for initial therapy. 3) Dabrafenib and Trametinib for patients with BRAF V600E mutations, which have demonstrated efficacy in various studies. These alternatives offer targeted approaches based on specific genetic mutations in NSCLC.

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Kinase Inhibitor

Avutometinib + Defactinib for Non-Small Cell Lung Cancer (RAMP202 Trial)

Phase 2

Waitlist Available

Led By Ross Camidge, MD, PhD

Research Sponsored by Verastem, Inc.

Eligibility Criteria Checklist

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

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug called avutometinib, alone or with defactinib, in patients with recurrent lung cancer who have specific genetic mutations and have not responded to standard treatments. The drugs aim to block pathways that help cancer cells grow and spread.

Who is the study for?

This trial is for adults with recurrent Non-small cell lung cancer (NSCLC) who have had prior treatments, measurable disease, and known KRAS or BRAF mutations. They must be in good physical condition (ECOG ≤ 1), able to use contraception, and have recovered from previous treatment side effects. People with severe heart or lung conditions, recent strong drug interactions, symptomatic brain metastases, certain ocular disorders or infections are excluded.

What is being tested?

The study tests the safety and effectiveness of avutometinib alone or combined with defactinib in treating NSCLC. It aims to see how well these drugs work on patients who've seen their cancer return and carry specific genetic changes (KRAS G12V mutation among others).

What are the potential side effects?

Potential side effects may include typical reactions to cancer medications such as nausea, fatigue, skin issues, muscle problems like rhabdomyolysis (muscle breakdown), liver function changes due to organ inflammation but specifics will depend on individual patient responses.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 5 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 5 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 5 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

To determine efficacy in KRAS-other (non-G12V) NSCLC

To determine the efficacy of avutometinib (VS-6766) in combination with defactinib in BRAF-MT NSCLC

To determine the optimal regimen, either avutometinib (VS-6766) monotherapy or avutometinib (VS-6766) in combination with defactinib, in KRAS-G12V NSCLC

+1 more

Secondary study objectives

Disease Control Rate (DCR)

Duration of Response (DOR)

Overall Response Rate per RECIST 1.1 as assessed by Investigator

+3 more

Awards & Highlights

No Placebo-Only Group

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

Trial Design

5Treatment groups

Experimental Treatment

Group I: Arm 5:avutometinib (VS-6766) in combination with defactinibExperimental Treatment1 Intervention

in patients with a NSCLC BRAF-non-V600E tumor

Group II: Arm 4: avutometinib (VS-6766) in combination with defactinibExperimental Treatment1 Intervention

in patients with a NSCLC BRAF-V600E tumor

Group III: Arm 3: avutometinib (VS-6766) in combination with defactinibExperimental Treatment1 Intervention

in patients with a NSCLC KRAS-other (non-G12V) tumor

Group IV: Arm 2: avutometinib (VS-6766) in combination with defactinibExperimental Treatment1 Intervention

in patients with a NSCLC KRAS-G12V tumor

Group V: Arm 1: avutometinib (VS-6766) monotherapyExperimental Treatment1 Intervention

in patients with NSCLC KRAS-G12V tumor

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

avutometinib (VS-6766)

2020

Completed Phase 2

~90

avutometinib (VS-6766) and Defactinib

2020

Completed Phase 2

~90

Do I qualify?Apply below to find out

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) often involve targeted therapies that inhibit specific molecular pathways critical for cancer cell survival and proliferation. Avutometinib (VS-6766) is a dual RAF/MEK inhibitor that targets the RAF/MEK/ERK signaling pathway, which is frequently activated in NSCLC due to mutations in genes like KRAS and BRAF. By inhibiting both RAF and MEK, Avutometinib can more effectively block this pathway, potentially reducing tumor growth and overcoming resistance mechanisms that limit the efficacy of single-agent therapies. This is crucial for NSCLC patients as it offers a more tailored and potentially more effective treatment option, especially for those with specific genetic mutations driving their cancer.

Clinical, genetic and pharmacological data support targeting the MEK5/ERK5 module in lung cancer.Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.New targeted treatments in lung cancer--overview of clinical trials.