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

Sponsor

Verastem, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT01951690

Collaborator

(none)

Enrollment

Locations

Arm

Duration (Months)

6.1

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non Small Cell Lung Cancer Lung Cancer	Drug: defactinib (VS-6063)	Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

55 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Sep 1, 2013

Actual Primary Completion Date :

Jun 1, 2016

Actual Study Completion Date :

Jun 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: VS-6063 (defactinib) Administered orally BID in a 21 day cycle	Drug: defactinib (VS-6063)

Arm

Intervention/Treatment

Experimental: VS-6063 (defactinib)

Administered orally BID in a 21 day cycle

Drug: defactinib (VS-6063)

Outcome Measures

Primary Outcome Measures

Demonstrate that VS-6063 (defactinib), will improve PFS at 12 weeks (PFS12) within each cohort. [From baseline through 12 weeks of treatment]

Secondary Outcome Measures

Evaluate the response rate (RR) [Every 6 weeks from baseline through the end of treatment, an expected average of 4 months]
RR is measured as the best overall response using Response Evaluation Criteria In Solid Tumors (RECIST), version 1.1.
Evaluate progression free survival [From the date of first treatment to the date of progression including death from any cause, expected average at least 4 months]
PFS will be estimated in each cohort using Kaplan-Meier product limit estimates.
Evaluate Overall Survival (OS) [OS will be calculated from the date of first treatment to the date of death from any cause, expected average of at least 12 months. Patients who did not experience death will be censored at the last follow-up time.]
OS in each cohort will be estimated using Kaplan-Meier product limit estimates.

Other Outcome Measures

Evaluation of the association between pharmacodynamic (PD) biomarkers and clinical outcomes (response rate, progression-free survival and overall survival) [Baseline PD biomarkers will be associated with the RR (collected every 6 weeks) and PFS, both with expected average of 4 months from first treatment to progression, and OS (expected average of 12 months from first treatment to date of death)]
Evaluate the safety and tolerability of VS-6063 (defactinib) [From start of treatment to end of treatment, an expected average of 4 months]
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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

≥ 18 years of age.
ECOG (Eastern Cooperative Oncology Group) Performance Score of 0 or 1.
Histologic or cytologic confirmation of non-small cell lung cancer (NSCLC)
Molecular characterization of the tumor demonstrating a KRAS mutation by a CLIA-certified assay. Adequate archival tissue, tissue core biopsy specimen, or DNA samples must be available for central testing of INK4a/Arf and p53 if not previously performed by a CLIA certified lab.
Documented evidence of distant metastasis or locoregional recurrence per required assessments within 28 days prior to starting study therapy.

Note: Histologic confirmation of metastatic disease is not required.

For patients with brain metastases, the following criteria must be met:

Previously untreated brain metastases that are asymptomatic and not requiring steroids are permitted.

Previously treated brain metastases are permitted if most recent CNS radiographic imaging demonstrates no evidence of CNS disease progression For patients with previously untreated brain metastases, Central Nervous System (CNS) imaging is required at the time of disease imaging throughout treatment.

At least one measurable disease site per RECIST v1.1.
Received a minimum of one course of treatment that included at least one platinum-based chemotherapy doublet for metastatic or locally recurrent disease.
Adequate hematologic function including ANC ≥ 1200/mm3, Hemoglobin ≥ 9 g/dL (transfusion is permitted), and platelets ≥ 100,000/mm3.
Adequate hepatic function including ALT ≤ 2.5 x upper limit of normal (ULN) if liver metastasis is NOT present or ≤ 5 x ULN if liver metastasis is present, and total bilirubin ≤ 1.5 x ULN.
QTc (corrected QT) interval < 480 msec.

Exclusion Criteria:

Presence of an activating EGFR (epidermal growth factor receptor) mutation or ALK (anaplastic lymphoma kinase) translocation in the tumor.
Radiotherapy (RT) completed within 14 days prior to the first dose of study therapy.
Known impairment of gastrointestinal function that would alter drug absorption.
Leptomeningeal metastasis.
Symptomatic or untreated brain metastases or spinal cord compression or any of these conditions requiring chronic steroids to control symptoms.
History or evidence of cardiac risk
Known history of malignant hypertension (severe hypertension >180/120 mmHg with end organ involvement.
Another active concurrent malignancy.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Colorado Cancer Center, Anschutz Medical Campus	Denver	Colorado	United States	80045
2	Winship Cancer Institute of Emory University	Atlanta	Georgia	United States	30322
3	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland	United States	21287
4	Washington University School of Medicine	St. Louis	Missouri	United States	63110
5	Knight Cancer Institute, Oregon Health and Science University	Portland	Oregon	United States	97239
6	University of Pittsburgh Medical Center Cancer Center	Pittsburgh	Pennsylvania	United States	15232
7	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
8	University of Texas Southwestern Medical Center	Dallas	Texas	United States	75390-8852
9	The University of Texas Health Science Center at San Antonio	San Antonio	Texas	United States	78229-3900