Defactinib for Cancer with NF2 Mutations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: CYP3A4 inhibitors

Disqualifiers: Stroke, GI bleeding, Gilbert's, 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: Up to 3 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a treatment called defactinib (Defactinib Hydrochloride) to determine if it can stop cancer growth in individuals with a specific genetic change known as the NF2 mutation. Defactinib blocks a protein that may promote cancer cell growth when this mutation is present. The trial aims to discover if defactinib can shrink the cancer or prevent it from worsening. This trial may suit those with an NF2 mutation who have no history of certain heart issues or prior treatment with similar drugs. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but you should avoid drugs or foods that strongly affect certain liver enzymes (CYP3A4 or CYP2C9). It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that defactinib is likely to be safe for humans?

Research has shown that defactinib, also known as VS-6063, has undergone testing in earlier studies to assess its safety in humans. One study examined the combination of defactinib with pembrolizumab and found it safe and manageable. This suggests that defactinib alone might also be well-tolerated.

Although defactinib remains under study, its safety record so far appears suitable for clinical trials. Patients in earlier studies handled it without serious side effects. Ongoing studies continue to monitor for any negative effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Defactinib is unique because it targets cancer with NF2 mutations by inhibiting focal adhesion kinase (FAK), a protein involved in tumor growth and survival. Unlike traditional chemotherapy, which attacks rapidly dividing cells broadly, defactinib specifically disrupts the signaling pathways that cancer cells rely on, potentially leading to fewer side effects. Researchers are excited about defactinib because it offers a targeted approach that could be more effective for patients with these specific genetic mutations, providing a more personalized treatment option.

What evidence suggests that defactinib might be an effective treatment for cancer with NF2 mutations?

Research has shown that defactinib might help treat cancers with NF2 mutations. In earlier studies, tumors with these mutations responded well to defactinib, which blocks a protein called FAK. This protein often aids cancer cell growth when NF2 mutations are present. Lab tests demonstrated that inhibiting FAK can slow or halt the growth of these tumors. While researchers continue to collect information from participants in this trial, these early results suggest that defactinib could potentially shrink or stop the growth of cancers with NF2 mutations. ^{3 4 6 7 8}

Who Is on the Research Team?

David M Jackman

Principal Investigator

ECOG-ACRIN Cancer Research Group

Are You a Good Fit for This Trial?

This trial is for cancer patients with a specific genetic change called NF2 mutation. They must have passed previous MATCH Protocol criteria, have no serious heart issues or uncontrolled high blood pressure, and not be allergic to defactinib. People with recent GI bleeding, Gilbert's syndrome, stroke history within 6 months, prior FAK inhibitor treatment like defactinib or certain drug/food interactions are excluded.

Inclusion Criteria

Patients must have met applicable eligibility criteria in the Master MATCH Protocol prior to registration to treatment subprotocol

My tumor has an NF2 mutation.

My recent ECG showed no significant heart issues.

Exclusion Criteria

I have never been treated with FAK inhibitors or participated in the COMMAND trial.

I do not have a history of Gilbert's syndrome.

I am not allergic to VS-6063 (defactinib) or similar drugs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

Treatment

Participants receive defactinib orally 400 mg twice daily on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Up to 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up occurs every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Up to 3 years

What Are the Treatments Tested in This Trial?

Interventions

• Defactinib Hydrochloride

Trial Overview The trial tests VS-6063 (defactinib hydrochloride), which may block the FAK protein that supports cancer cell growth in patients with NF2 mutations. The goal is to see if it can shrink these cancers or halt their progression.

How Is the Trial Designed?

Group I: Treatment (defactinib) Experimental Treatment 1 Intervention

Patients receive defactinib PO 400 mg BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04439331

Testing VS-6063 (Defactinib) as a Potential Targeted ... This phase II MATCH treatment trial identifies the effects of VS-6063 (defactinib) in patients whose cancer has a genetic change called NF2 mutation.

2. withpower.com withpower.com/trial/phase-3-neoplasms-7-2015-fe99a

Defactinib for Cancer with NF2 Mutations This trial tests defactinib, a drug that blocks a protein called FAK, in patients with advanced cancers that have an NF2 mutation. Researchers aim to see if ...

3. asco.org asco.org/abstracts-presentations/ABSTRACT341473

A phase 2 study of defactinib (VS-6063 ... Neurofibromatosis 2 (NF2)-inactivated tumors demonstrate increased sensitivity to FAK inhibition in preclinical models. Arm U evaluated the FAK inhibitor ...

4. clinicaltrials.eu clinicaltrials.eu/inn/defactinib/

Defactinib: A Promising Drug for Cancer Treatment Defactinib, also known as VS-6063, is an investigational drug being studied in clinical trials for its potential to treat various types of cancer.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11180135/

NF2: An underestimated player in cancer metabolic ... In this review, we consolidate the current knowledge on NF2 and examine the potential connection between cancer metabolism and tumor immunity in merlin- ...

6. clinicaltrials.gov clinicaltrials.gov/ct2/keydates/NCT04439331

Testing VS-6063 (Defactinib) as a Potential Targeted ... This phase II MATCH treatment trial identifies the effects of VS-6063 (defactinib) in patients whose cancer has a genetic change called NF2 mutation.

7. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2025/219616Orig1s000MultidisciplineR.pdf

219616Orig1s000 - accessdata.fda.gov Recommended. Indication(s)/Population(s). (if applicable). Treatment of adult patients with KRAS-mutated recurrent low-grade serous ovarian ...

8. mycancergenome.org mycancergenome.org/content/clinical_trials/NCT02758587/

Clinical Trial: NCT02758587 This study will explore whether defactinib (a FAK inhibitor) can be safely and tolerably combined with pembrolizumab (a PD-1 inhibitor) and ...