PURPOSE: VS-6063 (also known as defactinib or PF-04554878) is a 
second-generation inhibitor of focal adhesion kinase and proline-rich tyrosine 
kinase-2. This phase 1 study evaluated the safety and tolerability, 
pharmacokinetics, and clinical activity of VS-6063 in Japanese subjects with 
advanced solid tumor malignancies in a first-in-Asian study setting.
METHODS: VS-6063 was administered orally twice daily (b.i.d.) in 21-day cycles 
to cohorts of three subjects each with a standard 3 + 3 dose-escalation design 
until disease progression or unacceptable toxicity. Blood samples for 
pharmacokinetics were collected on Day 1 and 15. The assessments were performed 
using CTCAE v4.0 for adverse events (AEs), and the Response Evaluation Criteria 
In Solid Tumors, version v1.1 (RECIST v1.1) for tumor response.
RESULTS: Nine patients were treated across three dose levels (200-600 mg BID). 
No dose-limiting toxicities were observed at any dose level. Most frequent 
treatment-related AEs were Grade 1/2 unconjugated hyperbilirubinemia, fatigue, 
decreased appetite, and diarrhea. Only one subject in the 200 mg BID cohort 
experienced reversible and transient Grade 3 unconjugated hyperbilirubinemia. PK 
analyses confirmed that the exposure at the recommended Phase 2 dose (RP2D) of 
400 mg BID was comparable with exposures previously reported in non-Japanese 
subjects. Durable stable disease of approximately 24 weeks was confirmed in two 
subjects (malignant mesothelioma and rectal cancer).
CONCLUSIONS: VS-6063 was well tolerated at all dose levels investigated in this 
first-in-Asian study. These data support the administration of VS-6063 to 
Japanese subjects at the RP2D in clinical trials involving solid tumor 
malignancies.