Despite toxicity and no clear clinical benefit, non-metastatic recurrent prostate cancer (nmPC) is typically treated with medical castration in North America. SM88 is a non-toxic novel combination therapy based on the Warburg effect, with activity in a variety of cancers including prostate (JCO 2017 e Abstract1). End of phase 1 results demonstrated stable or rising testosterone levels while achieving CTC (circulating tumor cells) benefit and no radiographic progression events (JCO 2017e Abstract2). We now report phase II data.
Starting in Sept 2016, a prospective Phase Ib/II of SM88 (230mg po bid) enrolled recurrent nmPC with rising PSA (PCWG3 definition) and detectable CTCs, but no radiographically identified lesions.
8 (of 34 planned) subjects have completed at least 1 cycle (median 5, range 1-7). Mean age was 69.7 (62-80); all had prior ADT after curative intent RT (50%) or surgery (50%); no patient is currently on ADT. Mean testosterone level (T) was 581.4 ng/dL and rose or remained stable in the subjects except for one patient who entered the trial castrate (30% (n = 4); at up to 6 cycles, no PSA progression (PCWG3) and no radiographic progression was reported (n = 8). No subject required other toxic therapy (100% subsequent treatment free survival). Available preliminary neutrophile:lymphocyte ratio (N::L)(n = 6) improved while urinary NTx, bone specific AlkPhos and LDH trends were essentially unchanged.Table:
|subject #||cycles completed||T ng/dL||CTCs baseline||Max Decrease||N:L Max Decrease|
We propose that hormonal castration is not necessary for nmPC disease control based on a preliminary assessment of both Phase Ib and II data of SM88. CTCs and N::L were improved while maintaining normal T. These early biomarker indicators are consistent with the observed 100% radiographic progression free survival and avoidance of additional toxic therapy. A phase III RCT is planned for confirmation of these results.
Clinical trial identification
Legal entity responsible for the study
G. Del Priore, S. Hoffman, G. Sokol: Current or potential ownership of stock or options and/or salary support from Tyme Inc. W-T. Chen, H. Dong: Employee of Vitatex. Tyme Inc has a commercial relationship with Vitatex whereby Vitatex provides blinded results to the CRO supervising the ongoing clinical trial.