What side effects are associated with this type of intervention?

Common treatments for lung cancer, particularly those involving RAF/MEK inhibitors and KRAS G12C inhibitors, often have side effects such as fatigue, nausea, diarrhea, and skin reactions. For example, the combination of dabrafenib (a BRAF inhibitor) and trametinib (a MEK inhibitor) has been associated with pyrexia, nausea, and diarrhea. Additionally, treatments like crizotinib, which targets ALK and MET, can cause peripheral edema and gastrointestinal issues. Immunotherapies such as durvalumab may lead to pneumonitis, rash, and pruritus. These side effects vary in severity and frequency, and patients should discuss potential risks and management strategies with their healthcare provider.

What prior FDA approvals exist?

The FDA has approved several targeted therapies for lung cancer, including treatments that focus on specific genetic mutations. For instance, dabrafenib plus trametinib, a combination targeting BRAF V600E mutations, has shown significant efficacy in advanced NSCLC. Additionally, adagrasib, a KRAS G12C inhibitor, is being studied in combination with avutometinib (VS-6766), which targets RAF/MEK pathways. These therapies represent a personalized approach to treating lung cancer based on specific genetic alterations.

What other types of research exist?

Promising alternatives for lung cancer treatment in 2024 include: 1) Capmatinib and Tepotinib for MET exon-14-skipping mutations, 2) Afatinib, Dacomitinib, and Osimertinib for EGFR uncommon alterations (G719A, S768I, L861Q), and 3) Dabrafenib plus Trametinib for BRAF V600E mutations.

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G12C Inhibitor

Avutometinib + Adagrasib for Lung Cancer (RAMP204 Trial)

Phase 1 & 2

Recruiting

Research Sponsored by Verastem, Inc.

Eligibility Criteria Checklist

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

Must have

An Eastern Cooperative Group (ECOG) performance status ≤ 1

The subject must have received prior therapy with a KRAS G12C inhibitor and experienced progression

Must not have

Concurrent ocular disorders

Subjects with the inability to swallow oral medications

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 5 years

Awards & highlights

Summary

This trial is testing a combination of two drugs, avutometinib (VS-6766) and adagrasib, in patients with a specific type of lung cancer who have not responded to previous treatments. The drugs aim to stop the cancer cells from growing by blocking the signals that tell them to multiply. Adagrasib, a KRASG12C inhibitor, irreversibly and selectively binds KRASG12C, locking it in its inactive state.

Who is the study for?

This trial is for adults with a specific mutation in their lung cancer (KRAS G12C) who have tried but not responded to certain treatments. They should be relatively healthy, able to perform daily activities with ease, and must not have more than three previous cancer treatments or active infections like hepatitis or HIV.

What is being tested?

The study tests the combination of two drugs, avutometinib (VS-6766) and adagrasib, on patients whose non-small cell lung cancer has worsened after initial treatment. It aims to see if this drug combo is safe and works better for these patients.

What are the potential side effects?

Possible side effects may include typical reactions from cancer medications such as fatigue, digestive issues, skin problems, changes in blood counts leading to increased infection risk or bleeding tendencies. Specific risks related to these drugs will be monitored closely.

Eligibility Criteria

Inclusion Criteria

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

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I am fully active and can carry on all my pre-disease activities without restriction.

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I have been treated with a KRAS G12C inhibitor and my cancer has progressed.

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My cancer has a KRAS G12C mutation.

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My lung cancer diagnosis was confirmed by lab tests.

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I've had 1-3 treatments for advanced lung cancer.

Exclusion Criteria

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

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I have an eye condition.

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I cannot swallow pills.

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I have not had major surgery in the last 4 weeks.

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I needed treatment for brain metastases symptoms within the last 2 weeks.

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I have heart disease or severe lung problems.

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I have an active hepatitis B, C, or HIV infection.

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I have had rhabdomyolysis or lung disease in the past.

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

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

Part A: To determine RP2D for avutometinib(VS-6766) in combination with adagrasib

To determine the efficacy of the optimal regimen identified from Part A

Secondary outcome measures

Clinical Benefit Rate

Disease Control Rate (DCR)

Duration of Response (DOR)

+7 more

Trial Design

2Treatment groups

Experimental Treatment

Group I: avutometinib(VS-6766)+adagrasibExperimental Treatment1 Intervention

To determine the recommended phase 2 dose (RP2D) for VS-6766 in combination with adagrasib in G12C inhibitor exposed patients

Group II: avutometinib (VS-6766)+adagrasib RP2DExperimental Treatment1 Intervention

To determine the efficacy of the RP2D identified from Part A in G12C inhibitor exposed patients

0 / 12Eligibility 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

Common treatments for lung cancer often involve targeted therapies that inhibit specific genetic mutations and signaling pathways critical for cancer cell proliferation and survival. For instance, Avutometinib (VS-6766) targets the RAF/MEK pathway, while Adagrasib inhibits the KRAS G12C mutation. These targeted approaches are significant for lung cancer patients because they offer more personalized and effective treatment options, potentially leading to better outcomes and fewer side effects compared to traditional chemotherapy.

Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation.Trials to Overcome Drug Resistance to EGFR and ALK Targeted Therapies - Past, Present, and Future.Tailoring tyrosine kinase inhibitors to fit the lung cancer genome.