A phase II, open-label, multi-arm study of TAS-115 for castration-resistant prostate cancer patients with bone metastases.

Abstract

164 Background: TAS-115, a novel multi-kinase (eg, MET, VEGFR) inhibitor has also shown to inhibits Feline McDonough Sarcoma oncogene (FMS) kinase, Anti-tumor activity against bone metastases was observed in the preclinical and phase1 study. In this phase 2 study, the efficacy and safety of TAS-115 were evaluated in castration-resistant prostate cancer (CRPC) patients (pts) with bone metastases. Methods: This was a phase 2, open-label, multi-arm study for CRPC pts with bone metastases to evaluate the clinical anti-tumor activity of TAS-115. Pts who had visceral metastases were ineligible for this study. TAS-115 was given orally, once daily, and schedule of 5 days on/2 days off each week was repeated. This study had 2 cohorts (A and B). In cohort A, TAS-115 ranging from 200 to 400 mg/day with abiraterone acetate was given to pts prior to docetaxel. In cohort B, CRPC pts who had symptomatic bone metastases, post or unfit to docetaxel, were randomized in a 1:1 to 400 or 600 mg/day of TAS-115. The primary endpoint was bone scan index (BSI) response rate at week 12, defined as ≥ 30% decrease of BSI from baseline. BSI is a quantitative assessment of bone scan data calculated by software (BONE NAVI). Results: From Nov 2016 to Jul 2018, a total of 50 pts received TAS-115 (24 pts in cohort A and 26 pts in cohort B). BSI response rate at week 12 and best BSI response was 20.8 % and 37.5% in cohort A, and 15.4 % and 19.2% in cohort B, respectively. Any reduction of BSI was observed in 70.8% of cohort A and 61.5% of cohort B. In cohort B, pain was assessed using the Brief Pain Inventory short form and improvement was observed in 61.5% of pts. Furthermore, the reduction of bone-turnover marker (BAP, P1NP, NTx and TRACP-5b) were observed in both cohorts, but not PSA response. The major (≥ 10%) Grade 3/4 treatment-related adverse drug reactions were hypophosphataemia (21%) in cohort A, and anemia (23%), hypophosphataemia (12%) and neutrophil count decreased (12%) in cohort B. Conclusions: Preliminary anti-tumor activity to bone lesion and improved pain were observed in CRPC pts with bone metastases, and safety of TAS-115 was acceptable. TAS-115 could be a novel therapeutic agent with a favorable safety profile for CRPC with bone metastases. Clinical trial information: JapicCTI-163448.