Neoplasms

Heart and Blood Diseases

Blood and Lymph Conditions

Immune System Diseases

All Conditions

Ear, Nose, and Throat Diseases

Nervous System Diseases

Diseases and Abnormalities at or Before Birth

Rare Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Lymphoma

Neurofibromatosis 2

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Lymphosarcoma

Neurofibromatosis Type 2

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

Defactinib Hydrochloride

David M Jackman

This phase II MATCH treatment trial identifies the effects of VS-6063 (defactinib) in patients whose cancer has a genetic change called NF2 mutation. Defactinib may block a protein called FAK, which may be needed for cancer cell growth when NF2 mutations are present. Researchers hope to learn if defactinib will shrink this type of cancer or stop its growth.

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.

Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)

MATCH Treatment Subprotocol U: VS-6063 (Defactinib) in Patients With Tumors With NF2 Loss

ORR is defined as the percentage of patients whose tumors have a complete or partial response to treatment among eligible and treated patients. Objective response rate is defined consistent with Response Evaluation Criteria in Solid Tumors version 1.1, the Cheson (2014) criteria for lymphoma patients, and the Response Assessment in Neuro-Oncology criteria for glioblastoma patients. For each treatment arm, 90% two-sided binomial exact confidence interval will be calculated for ORR.

OS is defined as time from treatment start date to date of death from any cause. Patients alive at the time of analysis are censored at last contact date. OS will be evaluated specifically for each drug (or step) using the Kaplan-Meier method.

Progression free survival is defined as time from treatment start date to date of progression or death from any cause, whichever occurs first. PFS will be estimated using the Kaplan-Meier method.

National Cancer Institute (NCI)

Respiratory Tract (Lung and Bronchial) Diseases

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Digestive System Diseases

Skin and Connective Tissue Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Lung Neoplasms

Carcinoma

Prostatic Neoplasms

Stomach Neoplasms

Breast Neoplasms

Esophageal Neoplasms

Pancreatic Neoplasms

Carcinoma, Hepatocellular

Recurrence

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Urinary Bladder Neoplasms

Melanoma

Thyroid Neoplasms

Thyroid Diseases

Carcinoma, Renal Cell

Glioma

Uterine Neoplasms

Kidney Neoplasms

Colorectal Neoplasms

Endometrial Neoplasms

Rectal Neoplasms

Colonic Neoplasms

Skin Neoplasms

Neoplasms, Glandular and Epithelial

Disease Attributes

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Diseases

Neoplasms, Neuroepithelial

Endocrine System Diseases

Breast Diseases

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Endocrine Gland Neoplasms

Ovarian Diseases

Adnexal Diseases

Gonadal Disorders

Genital Neoplasms, Male

Genital Diseases, Male

Prostatic Diseases

Male Urogenital Diseases

Pancreatic Diseases

Head and Neck Neoplasms

Esophageal Diseases

Stomach Diseases

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Adenocarcinoma

Liver Neoplasms

Liver Diseases

Kidney Diseases

Stomach Cancer

Esophageal Cancer

Pancreatic Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Antineoplastic Agents

All Drugs and Chemicals

Vasoconstrictor Agents

Respiratory System Agents

Anti-Infective Agents

Anti-Arrhythmia Agents

Vasodilator Agents

Analgesics

Amino Acids

Osimertinib

Antibodies

Antibodies, Monoclonal

Trastuzumab

Epinephrine

Nivolumab

Piperazine

Mebendazole

Piperazine citrate

DMP 777

Immunoconjugates

Relatlimab

Immunoglobulins

Immunoglobulin G

Ipatasertib

Palbociclib

Sunitinib

Dasatinib

Afatinib

Trametinib

Dabrafenib

Crizotinib

Tyrosine Kinase Inhibitors

Immunoglobulins, Intravenous

Pertuzumab

Ado-Trastuzumab Emtansine

Racepinephrine

Epinephryl borate

Adenosine

Trastuzumab biosimilar HLX02

Adavosertib

GSK2636771

Maytansine

Immunologic Factors

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tubulin Modulators

Antimitotic Agents

Immunotoxins

Tyrosine

Patients with EGFR activating mutation receive afatinib orally (PO) once daily (QD) on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients may also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Patients with HER2 activating mutation receive afatinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with MET amplification receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation and collection of blood samples throughout the study. Patients may undergo biopsy at screening, on study, and/or at end of treatment.

Patients with MET exon 14 deletion or other mutations that disrupt exon 14 receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo tumor biopsy on study and undergo radiologic evaluation and blood sample collection throughout the study.

Patients with EGFR T790M or rare activating mutation receive osimertinib (AZD9291) PO QD on days 1-28 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO or multigated acquisition scan (MUGA) during screening, and biopsy and collection of blood samples on trial and at end of treatment.

Patients with ALK translocation receive crizotinib PO twice daily (BID) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with ROS1 translocation or inversion receive crizotinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with BRAF V600E/R/K/D mutation receive dabrafenib PO BID and trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with PIK3CA mutation without RAS mutation or PTEN loss receive taselisib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients receive pertuzumab IV over 30-60 minutes and trastuzumab IV over 30 minutes on day 1 of each cycle. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Patients also undergo radiologic evaluation throughout the trial, ECHO at screening and end of treatment, and biopsy and collection of blood samples on trial and at end of treatment.

Patients with FGFR amplification receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo CT and MRI throughout study. Patients may also undergo blood sample collection and tumor biopsy throughout the trial.

Patients with FGFR mutation or fusion receive erdafitinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo blood sample collection, CT or MRI, and tumor biopsy throughout the study.

Patients with mTOR mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients with TSC1 or TSC2 mutation receive sapanisertib PO daily on days 1-28. Cycles repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Patients with PTEN mutation or deletion and PTEN expression receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with PTEN loss receive PI3K-beta inhibitor GSK2636771 PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with HER2 amplification receive trastuzumab emtansine intravenously (IV) over 30-90 minutes on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Patients with BRAF fusion or BRAF non-V600 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with NF1 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with GNAQ or GNA11 mutation receive trametinib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with SMO or PTCH1 mutation receive vismodegib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo ECHO or nuclear study during screening, tumor biopsy on study and CT scan, MRI and blood sample collection throughout the study.

Patients with NF2 inactivating mutation receive defactinib PO BID on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients with cKIT exon 9, 11, 13, or 14 mutation receive sunitinib PO QD on days 1-28 of each cycle. Cycles repeat every 42 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT or MRI during screening and on study, as well as during follow-up as clinically necessary. Patients also undergo ECHO or nuclear study throughout the trial as clinically necessary. Patients undergo biopsies and blood sample collection on study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
Testing VS-6063 (Defactinib) as a Potential Targeted Treatment in Cancers With NF2 Genetic Changes (MATCH-Subprotocol U)	NCT04439331	Advanced Lympho... Advanced Malign... Hematopoietic a... Refractory Lymp... Refractory Mali... Refractory Mult...	Defactinib Hydr...	18 Years -	National Cancer Institute (NCI)
Targeted Therapy Directed by Genetic Testing in Treating Patients With Advanced Refractory Solid Tumors, Lymphomas, or Multiple Myeloma (The MATCH Screening Trial)	NCT02465060	Advanced Lympho... Advanced Malign... Bladder Carcino... Breast Carcinom... Cervical Carcin... Colon Carcinoma Colorectal Carc... Endometrial Car... Esophageal Carc... Gastric Carcino... Glioma Head and Neck C... Hematopoietic a... Kidney Carcinom... Liver Carcinoma Lung Carcinoma Lymphoma Malignant Uteri... Melanoma Multiple Myelom... Ovarian Carcino... Pancreatic Carc... Prostate Carcin... Rectal Carcinom... Recurrent Bladd... Recurrent Breas... Recurrent Cervi... Recurrent Colon... Recurrent Color... Recurrent Esoph... Recurrent Gastr... Recurrent Gliom... Recurrent Head ... Recurrent Liver... Recurrent Lung ... Recurrent Lymph... Recurrent Malig... Recurrent Melan... Recurrent Multi... Recurrent Ovari... Recurrent Pancr... Recurrent Prost... Recurrent Recta... Recurrent Skin ... Recurrent Thyro... Recurrent Uteri... Refractory Lymp... Refractory Mali... Refractory Mult... Skin Carcinoma Thyroid Gland C... Uterine Corpus ...	Adavosertib Afatinib Afatinib Dimale... Binimetinib Biopsy Biospecimen Col... Capivasertib Computed Tomogr... Copanlisib Copanlisib Hydr... Crizotinib Cytology Specim... Dabrafenib Dabrafenib Mesy... Dasatinib Defactinib Defactinib Hydr... Echocardiograph... Erdafitinib Fexagratinib Ipatasertib Laboratory Biom... Larotrectinib Larotrectinib S... Magnetic Resona... Multigated Acqu... Nivolumab Osimertinib Palbociclib Pertuzumab PI3K-beta Inhib... Radiologic Exam... Radionuclide Im... Relatlimab Sapanisertib Sunitinib Malat... Taselisib Trametinib Trastuzumab Trastuzumab Emt... Ulixertinib Vismodegib	18 Years -	National Cancer Institute (NCI)

Spots Global Cancer Trial Database for defactinib hydrochloride