Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Symptoms and General Pathology

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Tissue Adhesions

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Administered orally BID in a 21 day cycle

defactinib (VS-6063)

David E Gerber, M.D.

This is a Phase II, open-label, multicenter, multi cohort, study of VS-6063 (defactinib), a focal adhesion kinase inhibitor, in patients with KRAS mutant non-small cell lung cancer (NSCLC). NSCLC with a KRAS mutation is required for study entry and subjects will be enrolled into 1 of 4 cohorts based on the status of their INK4a/Arf and p53 mutations. The purpose of this study is to demonstrate if VS-6063 (defactinib) improves PFS within each cohort. The safety and tolerability of VS-6063, tumor response rate, progression free survival and overall survival will also be assessed. The pharmacodynamic effects of VS-6063 (defactinib) will be examined in a tumor biopsy and a blood sample.

Eleven subjects will be enrolled into one of four cohorts: Cohort A (KRAS mutation, wild type INK4a/ARF and wildtype p53), Cohort B (KRAS mutation, INK4s/ARF mutation and wild type p53), Cohort C (KRAS mutation, wild type INK4a/ARF and p53 mutation), and Cohort D (KRAS mutation, INK4a/ARF mutation and p53 mutation). If \>/= 4 patients demonstrate PFS at 12 weeks in each cohort, an additional 23 subjects will be enrolled.

Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer

Phase II Study of VS-6063, A Focal Adhesion Kinase (FAK) Inhibitor, in Patients With KRAS Mutant Non-Small Cell Lung Cancer

Adverse events (AEs) include the incidences of all treatment-emergent AEs (TEAEs) and all Serious Adverse Events (SAEs); by severity, relationship to study drug, and discontinuation of patients from study therapy due to AEs and due to deaths. Safety endpoints for AEs, clinical laboratory tests, vital signs, ECGs and physical examinations will be summarized using descriptive statistics as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.

PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.

OS in each cohort will be estimated using Kaplan-Meier product limit estimates.

Verastem, Inc.

Neoplasm Metastasis

Neoplastic Processes

Oral VS-4718 administered BID (QD during first cohort) during a 28 day cycle.

VS-4718

Hagop Youssoufian, MD

This is a Phase I, open-label, multicenter, dose-escalation trial of VS-4718, a focal adhesion kinase inhibitor, in subjects with metastatic non-hematologic malignancies. This clinical study is comprised of 2 parts: Part 1 (Dose Escalation) and Part 2 (Expansion). The purpose of this study is to evaluate the safety (including the recommended Phase II dose), pharmacokinetics (the amount of VS-4718 in your blood) and the anti-cancer activity of VS-4718. The pharmacodynamic effects (genes or proteins that may predict or show how your body may respond to VS-4718) will also be examined in tumor biopsies and blood samples.

Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies

A Phase I Study of VS-4718, a Focal Adhesion Kinase Inhibitor, in Subjects With Metastatic Non-Hematologic Malignancies

Serious Adverse events, Adverse events and their frequency, duration and severity, physical examination, laboratory parameters, vital signs and ECGs as determined based on CTCAE (Common Toxicity Criteria for Adverse Effects) V4.03. A Safety monitoring committee will review safety information.

The RP2D will be determined based on the maximum tolerated dose (MTD) of VS-4718 as determined by number of participants with dose limiting toxicities related to VS-4718. Observations related to pharmacokinetics, pharmacodynamics, and any VS-4718 related toxicities may be included in the rationale supporting the RP2D and will not exceed the MTD.

Response rate and progression-free survival as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

PK (pharmacokinetics) parameters, including but not limited to clearance, plasma concentration, AUC (Area Under Curve, 0-24 and 0-t), Cmax, Tmax, and T1/2

Pre and post dose biomarker analysis in serum and tumor samples to identify possible prognostic factors to VS-4718 response

Tumor expression status (pFAK, cancer stem cells, CSC, and other biomarkers) compared with response to VS-4718, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

Oral defactinib (VS-6063) administered twice a day (BID) during a 21 day cycle.

Defactinib

Hagop Youssoufian, m

This is a phase I, open-label, dose-escalation trial of defactinib (VS-6063), a focal adhesion kinase inhibitor, in Japanese patients with non-hematologic malignancies. The purpose of this study is to assess the safety (including the recommended phase 2 dose), the pharmacokinetics, and the anti-cancer activity of defactinib (VS-6063).

Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies

A Phase I Dose Escalation Study to Evaluate the Safety and Pharmacokinetics of VS-6063, a Focal Adhesion Kinase Inhibitor, in Japanese Subjects With Non-Hematologic Malignancies

A composite by dose level to include incidence of AEs, SAEs, dose interruptions and dose reductions as a measure of safety and tolerability. Abnormal Clinical significant laboratory results, ECG measurements, vital signs measurement, physical examination findings, and ECOG performance status were captured as adverse events.

The severity of AEs were evaluated according to CTCAE (Common Toxicity Criteria for Adverse Effects) 4.03

The RP2D will be determined based on the MTD of defactinib (VS-6063) as determined by number of participants with dose limiting toxicities (DLTs) related to defactinib.

PK parameters, including but not limited to plasma concentration, AUC (Area Under Curve) 0-t, Cmax, Tmax, and T1/2. Total 24-hour urine output will be collected in conjunction with PK sampling to assess the elimination of defactinib (VS-6063) and its potential metabolites.

Response rate and progression-free survival, as determined by Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1

The systematic method was through regular investigator assessment and regular laboratory testing.

Defactinib 200 mg Bid

Defactinib 400 mg Bid

Defactinib 600 mg Bid

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

Lou Vaickus, MD, FACP/Chief Medical Officer

At least 1 TEAE (treatment emergent AE)

At least 1 TEAE related to study drug

Non-Lab TEAE with Severity ≥ Grade 3

Lab TEAE with Severity ≥ Grade 3

At least 1 Serious TEAE

Dose Interruptions

Dose Reductions

Assess the Safety and Tolerability of Defactinib (VS-6063) in Japanese Subjects With Non-hematologic Malignancies

Define the Maximum Tolerated Dose (MTD), if Achieved, and Establish the Recommended Phase 2 Dose (RP2D) of Defactinib (VS-6063) in Japanese Subjects.

Assess the Pharmacokinetics, Metabolism and Elimination of Defactinib (VS-6063) in Plasma and Urine.

Evaluate the Efficacy (Response Rate and Progression-free Survival) of Subjects Treated With Defactinib (VS-6063).

200 mg bid (twice a day) po (by mouth) defactinib

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase II Study of VS-6063 in Patients With KRAS Mutant Non-Small Cell Lung Cancer	NCT01951690	Non Small Cell ... Lung Cancer	defactinib (VS-...	18 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies	NCT01849744	Non Hematologic... Metastatic Canc...	VS-4718	18 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies	NCT01943292	Non Hematologic...	Defactinib	20 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-4718 in Subjects With Metastatic Non-Hematologic Malignancies	NCT01849744	Non Hematologic... Metastatic Canc...	VS-4718	18 Years -	Verastem, Inc.
Phase I Dose Escalation Study of VS-6063 in Japanese Subjects With Non-Hematologic Malignancies	NCT01943292	Non Hematologic...	Defactinib	20 Years -	Verastem, Inc.

Spots Global Cancer Trial Database for fak inhibitor