A randomized, multicenter, international phase II study of tasquinimod in chemotherapy naïve patients with metastatic castrate-resistant prostate cancer (CRPC).

Abstract

4510 Background: Tasquinimod (TASQ) is a quinoline-3-carboxamide derivative that binds to S100A9 and displays anti-angiogenic properties and anti-tumor activity in prostate cancer (PC) models. Phase I studies in PC indicated that TASQ is well tolerated and may delay PC progression. Methods: 206 patients (pts) with metastatic CRPC were assigned (2:1) to either receive oral TASQ once-daily at an initial dose level of 0.25 mg/day escalating to 1.0 mg/day over 4 weeks, or placebo (P). The primary endpoint was proportion of pts without disease progression (DP) at 6 months, defined by PCWG2 or pain criteria, but excluding PSA. Secondary endpoints comprised safety, progression free survival (PFS), and changes in biological markers, including PSA. Results: 200 (133 TASQ, 67 P) pts with a median age of 72.5 years were evaluable for efficacy and safety. Median baseline characteristics were (TASQ/P): Karnofsky (95/95), Gleason (7/7), LDH (201/206 U/L), Alk Phos (98/87 U/L), Hgb (12.9/13.2 g/dL), PSA (29/19 μ g/L) and PSADT (4.2/5.0 mo). 6-mo progression free proportion for TASQ and P groups was 57% and 33% respectively (p=0.0001) and median PFS was 24.7 vs. 12.9 weeks. In clinical subgroups defined by PCWG2, the PFSs were (weeks/N): nodal 24.3/9 vs. 12.6/12; bone 30.6/90 vs. 13.4/42; visceral 23.9/32 vs. 12.1/10 for pts on TASQ and P. Pts treated with TASQ had significantly decreased serum LDH levels and stabilized bone alkaline phosphatase (BAP) levels, with less pronounced effects on PSA response and progression. Serious vascular events were more common in the TASQ arm (myocardial infarction, heart failure or stroke (3 % vs 0 %), deep vein thrombosis (4 % vs 0 %)). Common (>10%) adverse events (AEs) occurring more frequently in pts receiving TASQ included gastrointestinal disorders, fatigue, and musculoskeletal pains. and asymptomatic elevation of pancreatic enzymes and proinflammatory markers. G3-4 AEs (including labs) were reported in 38% pts on TASQ vs. 10 % on P. Conclusions: TASQ significantly slowed the rate of DP and improved PFS in pts with metastatic CRPC and a phase III study is planned. Side effects were manageable. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Active Biotech Active Biotech Active Biotech Active Biotech