Avutometinib + Defactinib for Stomach Cancer

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Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ryan H. Moy, MD, PhD

Must not be taking: Warfarin, Strong CYP3A4, others

Disqualifiers: Brain metastases, Hepatitis, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks per cycle

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a new combination of two drugs, avutometinib (VS-6766) and defactinib (VS-6063), can extend life and reduce tumor size in people with a specific type of stomach cancer. The trial also aims to ensure the treatment's safety. It targets individuals with diffuse-type stomach cancer who have already tried at least one treatment involving certain chemotherapy drugs. Participants must have visible cancer on scans and be in good general health otherwise. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but you cannot take certain drugs that interact with the study medications, like strong CYP3A4, CYP2C9, P-glycoprotein, or breast cancer resistance protein inhibitors or inducers. If you're on warfarin, you may need to switch to a different blood thinner.

Is there any evidence suggesting that the combination of Avutometinib and Defactinib is likely to be safe?

Research shows that the combination of avutometinib and defactinib is under study to assess its safety. Some studies have examined how well patients tolerate these drugs. Results suggest that while the combination can be challenging, it is often manageable. Patients have experienced side effects, which is common with many cancer treatments. However, these side effects are usually not severe and can often be controlled.

Both avutometinib and defactinib have been tested separately in other studies, demonstrating some ability to fight cancer cells. These drugs have undergone several rounds of testing, aiding researchers in understanding their safety in humans. Since this remains an experimental treatment, anyone considering joining a trial should consult their doctor to understand all the risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Avutometinib and Defactinib for stomach cancer because they work differently from standard chemotherapy treatments. Unlike traditional options that target rapidly dividing cells, Avutometinib inhibits specific proteins involved in cancer cell growth, while Defactinib targets cancer cell survival pathways. This targeted approach may lead to more effective treatment with potentially fewer side effects. By focusing on these unique mechanisms, these drugs offer a fresh approach to tackling stomach cancer, which is why there's a buzz around them in the medical community.

What evidence suggests that the combination of Avutometinib and Defactinib might be an effective treatment for stomach cancer?

Research has shown that the combination of the drugs avutometinib and defactinib, which participants in this trial will receive, may help treat diffuse gastric cancer. Studies have found that this combination can effectively shrink tumors. In early tests, this treatment led to significant tumor reductions, indicating that the two drugs work well together. Additionally, patients with advanced stages of this cancer experienced improvements when treated with this combination. These findings suggest that the treatment could help extend life and reduce tumor size in stomach cancer patients. ^{1 2 3 6 7}

Who Is on the Research Team?

Ryan Moy, MD, PhD

Principal Investigator

Columbia University

Are You a Good Fit for This Trial?

This trial is for individuals with diffuse-type stomach cancer. Participants should not have had prior treatment for their condition and must be in a health state that allows them to undergo the study treatments.

Inclusion Criteria

I have recovered from previous cancer treatment side effects.

I have been treated with platinum and fluoropyrimidine for my advanced cancer.

I am fully active or can carry out light work.

Exclusion Criteria

I do not have severe heart or lung conditions.

Any other medical condition that in the opinion of the investigator would place the subject at unacceptably high risk for toxicity.

I am not taking any medications or supplements that could interfere with the study treatment.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Avutometinib 3.2mg orally two times per week for three weeks followed by one week of rest, and Defactinib 200mg twice daily for three weeks followed by one week of rest

4 weeks per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Long-term follow-up

Participants are monitored for overall survival and progression-free survival

Up to 5 years

What Are the Treatments Tested in This Trial?

Interventions

• Avutometinib
• Defactinib

Trial Overview The trial is testing if taking avutometinib together with defactinib helps people live longer, shrinks tumors, and is safe for patients with diffuse gastric cancer.

How Is the Trial Designed?

Group I: Avutometinib & Defactinib Experimental Treatment 2 Interventions

Avutometinib: Study participants will receive Avutometinib 3.2mg orally two times per week for three weeks in a row followed by one week of rest Defactinib: Study participants will receive Defactinib 200mg twice daily for three weeks in a row followed by one week of rest

Who Is Running the Clinical Trial?

Ryan H. Moy, MD, PhD

Lead Sponsor

Trials

1

Recruited

30+

Verastem Oncology

Collaborator

Trials

2

Recruited

90+

Verastem, Inc.

Industry Sponsor

Trials

42

Recruited

2,800+

Citations

1. ascopubs.org ascopubs.org/doi/10.1200/JCO.2025.43.4_suppl.TPS505

Phase 2 trial of defactinib in combination with avutometinib ... The goal of this study is to investigate the efficacy and tolerability of avutometinib plus defactinib in patients with advanced DGC refractory to standard ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06487221

Avutometinib and Defactinib in Diffuse Gastric Cancer The purpose of this study is to determine if the combination study treatment with defactinib and avutometinib is effective in improving the length of time after ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-04532

Avutometinib with Defactinib for the Treatment of Patients ... This phase II trial tests how well avutometinib and defactinib work in treating patients with diffuse gastric cancer that that has spread from where it first ...

4. researchgate.net researchgate.net/publication/388609801_Phase_2_trial_of_defactinib_in_combination_with_avutometinib_in_patients_with_advanced_diffuse-type_gastric_cancer

Phase 2 trial of defactinib in combination with avutometinib ... In preclinical DGC xenograft models, defactinib plus the RAF/MEK clamp avutometinib led to deep tumor regressions, suggesting synergistic activity of the ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11378359/

Preclinical evaluation of avutometinib and defactinib in ... Avutometinib, defactinib, and to a larger extent their combinations, demonstrated promising in vitro and in vivo activity against EAC cell lines and xenografts.

6. cancerresearchuk.org cancerresearchuk.org/about-cancer/find-a-clinical-trial/a-trial-looking-at-the-drugs-defactinib-with-vs-6766-for-all-cancers-frame

A trial looking at the drugs defactinib with VS-6766 for all ... They work by blocking messages that tell cancer cells to grow. We know from research that defactinib by itself and VS-6766 by itself work against cancer.

7. georgiacancerinfo.org georgiacancerinfo.org/clinical-trials/detail/5652

A Study of Avutometinib (VS-6766) + Defactinib (VS-6063) ... Further assess safety of a drug in a large sample of patients. The study drug is tested among patients with a specific cancer type and new combinations of drugs ...