Clinical Trial Finder

Inclusion Criteria:

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

• - Patients must have a tumor that harbors an inactivating mutation in NF2.

• - Patients must have an electrocardiogram (ECG) within 8 weeks prior to treatment assignment and must have no clinically important abnormalities in rhythm, conduction or morphology of resting ECG (e.g. complete left bundle branch block, third degree heart block) - Patients with known left ventricular dysfunction must have echocardiogram (ECHO) or a nuclear study (multigated acquisition scan [MUGA] or First Pass) within 4 weeks prior to registration to treatment and must not have left ventricular ejection fraction (LVEF) < institutional lower limit of normal (LLN).

If the LLN is not defined at a site, the LVEF must be > 50% for the patient to be eligible.

• - Patients with history of hypertension should be adequately controlled (blood pressure [BP] < 140/90) with appropriate anti-hypertensive therapy or diet.

Exclusion Criteria:

• - Patients must not have known hypersensitivity to VS-6063 (defactinib) or compounds of similar chemical or biologic composition.

• - Patients must not have a history of upper gastrointestinal (GI) bleeding, ulceration, or perforation within 12 months prior to the first dose of study drug.

• - Patients must not have known history of Gilbert's syndrome.

• - Patient must not have a known history of stroke or cerebrovascular accident within 6 months prior to the first dose of VS-6063 (defactinib) - Patients must not have prior treatment with a FAK inhibitor (e.g., VS-6063 [defactinib] or GSK2256098) and must not be participating or have participated in the COMMAND trial of maintenance therapy of VS-6063 (defactinib) versus (vs.) placebo, for mesothelioma.

• - Patients must not be using drugs or foods that are known potent CYP3A4 or CYP2C9 inhibitors or inducers.

Substrates of CYP3A4, 2C9, UGT1A1, P-gp, OATP1B1, and OATP1B3 should be used with caution

PRIMARY OBJECTIVE:

• I. To evaluate the proportion of patients with objective response (OR) to targeted study agent(s) in patients with advanced refractory cancers/lymphomas/multiple myeloma.

SECONDARY OBJECTIVES:

• I. To evaluate the proportion of patients alive and progression free at 6 months of treatment with targeted study agent in patients with advanced refractory cancers/lymphomas/multiple myeloma.

• II. To evaluate time until death or disease progression.

• III. To identify potential predictive biomarkers beyond the genomic alteration by which treatment is assigned or resistance mechanisms using additional genomic, ribonucleic acid (RNA), protein and imaging-based assessment platforms.

• IV. To assess whether radiomic phenotypes obtained from pre-treatment imaging and changes from pre- through post-therapy imaging can predict objective response and progression free survival and to evaluate the association between pre-treatment radiomic phenotypes and targeted gene mutation patterns of tumor biopsy specimens.

OUTLINE: Patients receive defactinib hydrochloride (defactinib) orally (PO) twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up every 3 months if less than 2 years from study entry, and then every 6 months for year 3 from study entry.

Arms

Experimental: Treatment (defactinib)

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

Interventions

Drug: - Defactinib Hydrochloride

Given PO