922P - A Phase II Study of SB939 in Patients (PTS) with Castration Resistant Prostate Cancer (CRPC)

Abstract

ABSTRACT Background SB939 is a potent oral inhibitor of class 1, 2, and 4 histone deacetylases (HDACs). These 3 HDAC classes are highly expressed in CRPC and associated with poor clinical outcomes. HDAC inhibition abrogates androgen receptor signaling via inactivation of HSP90, and may have particular relevance in prostate cancer with the TMPRSS2-ERG (T2-E) fusion. Methods Pts with locally recurrent or metastatic CRPC received SB939 60mg every other day 3 times per week x 3 weeks on a 28-day cycle. Primary endpoints were PSA response rate (RR) (>50% decline from baseline for > 4 weeks) and progression-free survival (PFS). Secondary endpoints included objective response rate and duration; overall survival; circulating tumor cell (CTC) enumeration at baseline, 6 and 12 weeks; T2-E fusion analysis; correlative analysis of archival tissue; and safety. In a 2-stage design, a planned maximum of 29 response evaluable patients were to be enrolled. Results 32 pts were enrolled and have completed study treatment. Median age was 70; 88% of pts had received no prior chemotherapy; and ECOG performance status was 0/1 in 44%/56%. Bone/lymph node/visceral metastases were present in 91%/75%/12%. The median number of SB939 cycles administered was 3 (range 1-8). Adverse events were generally grade 1-2, with 5 pts experiencing one or more grade 3 events (fatigue (5), vomiting (1), dyspnea (1)). One pt died due to myocardial infarction. A confirmed PSA response was noted in 2 pts (6%), lasting 3.0 and 9.4 mo. In 16 pts with measurable disease, there were no objective responses, 7 pts had stable disease lasting 1.6 to 8.0 months. CTC response (from ≥5 at baseline to 5 at 6 weeks correlated with PSA progression. Correlative studies to evaluate T2-E from whole blood as well as T2-E fusion and PTEN deletion status on archival tissue are ongoing. Conclusion SB939 is tolerable at the dose/schedule given, but does not merit further study as a single agent in CRPC based on PSA RR. Activity was observed in terms of CTC declines however. Study of SB939 with cytotoxic or AR targeted therapies may be warranted. Supported by grants from the Canadian Cancer Society and the Ontario Institute for Cancer Research. Disclosure All authors have declared no conflicts of interest.