Window of Opportunity Study of VS-6063 (Defactinib) in Surgical Resectable Malignant Pleural Mesothelioma Participants

Study Overview
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Brief Summary
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This is an open label neoadjuvant (treatment with VS-6063 prior to mesothelioma surgery) study in subjects with malignant pleural mesothelioma who are eligible for surgery. Subjects will receive VS-6063 (defactinib) 400 mg twice daily for 12, 21, or 35 days or 100 mg formulation twice daily for 21 days. Pre- and post-treatment biopsies and blood samples will be collected. The purpose of this study is to assess biomarker responses from tumor tissue. The safety, pharmacokinetics, and tumor response rate to VS-6063 (defactinib) will be also be assessed.

Official Title
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An Open Label Window of Opportunity Phase II Study of the FAK Inhibitor Defactinib VS-6063 in Participants With Surgical Resectable Malignant Pleural Mesothelioma.

Conditions
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Malignant Pleural Mesothelioma

Intervention / Treatment
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* Drug: VS-6063


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically confirmed malignant pleural mesothelioma that is not metastatic or unresectable Eligible to undergo excisional surgery such as pleurectomy/decortication (P/DC) or any other mesothelioma surgery. Localized disease. The malignancy is confined to one affected hemithorax. Mediastinal N2 lymph nodes via cervical mediastinoscopy or EBUS (endobronchial ultrasound) must be negative in order to be eligible Grossly normal pulmonary, cardiac function, renal, hepatic hematologic and performance functions Male or non-pregnant female Age ≥ 18 years of age Tissue is required prior to enrollment. If patient was diagnosed outside and tumor tissue is not available, a pleural biopsy for frozen tissue collection is required. Exclusion Criteria: Participants who have had chemotherapy or radiotherapy any time prior to entering the study or at any prior time for mesothelioma. Patients receiving chemotherapy type drugs for benign conditions can participate in this trial History of upper gastrointestinal bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug Known history of Gilbert's Syndrome or any current hyperbilirubinemia of any cause Known history of stroke or cerebrovascular accident within 6 months prior to the first dose of study drug Subjects with known infection with human immunodeficiency virus (HIV) or Acquired Immune Deficiency Syndrome (AIDS) Subjects with confirmed Hepatitis A, B or C Subjects being actively treated for a secondary malignancy or any malignancy within the last 3 years, with the exception of non-melanomatous skin cancer or localized, definitively treated cervical cancer. Men under observation for local prostate cancer are also eligible if they have had stable disease for at least 1 year. Uncontrolled or severe cardiovascular disease, including myocardial infarct or unstable angina within 6 months prior to study treatment, New York Heart Association (NYHA) Class II or greater congestive heart failure, serious arrhythmias requiring medication for treatment, clinically significant pericardial disease, or cardiac amyloidosis Known history of malignant hypertension Uncontrolled intercurrent illness including symptomatic congestive heart failure, cardiac arrhythmia, or psychiatric illness/social situations which in the opinion of the study investigators would be associated with undue risk of participation in the study Use of an investigational drug within 28 days or 5 half-lives prior to first dose. Pregnant or breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VS-6063 (defactinib)<br>Administered orally (BID) for 12, 21 or 35 days (+/- 2 days) | Drug: VS-6063<br> <br> * Other names: defactinib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess biomarker responses to VS-6063 in tumor tissue | To determine biomarker responses to the Focal Adhesion Kinase (FAK) inhibitor, VS-6063 (defactinib), in Malignant Pleural Mesothelioma (MPM). | From Baseline to 12, 21 or 35 days (+/- 2 days) post-treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluate the safety of VS-6063 (defactinib) | Adverse events will be graded by the CTCAE (Common Terminology Criteria for Adverse Events) 4.0 and summarized according to the worst grade observed since the first treatment dose. | Start of treatment through 30 days after the end of treatment, expected average of 6-8 weeks | 
| Evaluate the pharmacokinetics of VS-6063 (defactinib) | PK (pharmacokinetic) parameters will include but not limited to peak and trough concentrations and AUC (area under curve), clearance, and elimination half-life will be characterized by average and variation summaries in the population. | Day 11 and Day 12, Day 21 and 28, or Day 35 and 42 (+/-2) days post-treatment | 
| To evaluate the tumor response to VS-6063 (defactinib) | Tumor response will be assessed by Recist 1.1 modified for mesothelioma. The response rate will be reported with 95% exact confidence intervals based on the exact binomial distribution. | Baseline and 12, 21 or 35 (+/-2) days post-treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mesothelioma, adenoma, Neoplasms, Mesothelial, Focal Adhesion Kinase Inhibitor