719PPhase II monotherapy efficacy of cancer metabolism targeting SM-88 in heavily pre-treated PDAC patients

Abstract Background SM-88 (D,L-alpha-metyrosine; racemetyrosine [USAN]) is a relatively non-toxic, targeted therapy based on the Warburg Effect. It may be well suited for pancreas cancer because of its ability to penetrate tumors and tolerability in compromised patients. Methods Subjects progressed on at least one line of chemotherapy were randomized to receive either 460 mg/d or 920 mg/d single agent SM-88 administered with low doses of methoxsalen, phenytoin, and sirolimus (MPS) in the dose selecting stage of this trial. The primary endpoint is response rate by BICR. Results As of April 2019, 49 subjects with stage IV pancreatic ductal adenocarcinoma with radiographically documented progressive disease were enrolled and randomized. Mean age was 66 (45 – 85); median of 2 prior lines (1 – 5+); baseline median CA19.9 was 2,674 (0.8 – 651,696). There were 22 disease related SAEs before drug treatment, including 6 Grade 5 events. SM-88 was well tolerated with only four treatment-related Grade 3/4 adverse events in two subjects (and no treatment-related Grade 5 events). 94% of treated subjects (46/49) experienced a total 365 AEs, with only 17% (63/365) at least possibly treatment related. CTCs at baseline were detected in 100% (mean 138 cells/4 ml) and fell in 79% (23/29) evaluable subjects from 153 to a nadir of 54 cells/4 ml (median reduction 63% [18% - 100%]). 12% (4/33) evaluable subjects showed CA19.9 declines (-8% to –97% decline within 3 months), three of which also showed CTC declines. Subjects have remained on treatment a median of 6.9 wks (1.7 – 23.1). While progressive upon entry, 21% (8 of 38 evaluable subjects) displayed stable disease or better at 2 months or beyond. Of the 38 evaluable subjects, 42% (16/38) were alive at 4 months post randomization, and 24% (9/38) were alive at 6 months, which parallels carry over effect previously observed with SM-88. EORTC QLQ-C30, -PAN26, and correlative assays were obtained including leptin, genomics, and NLR. Conclusions SM-88 demonstrated unconfirmed monotherapy effect with no meaningful toxicity in a preliminary assessment of this ongoing trial. With additional follow up, dose and patient populations will be selected for expansion. Clinical trial identification NCT03512756. Legal entity responsible for the study Tyme Inc. Funding Tyme Inc. Disclosure A. Ocean: Advisory / Consultancy: Tyme Inc. M. Noel: Advisory / Consultancy: Tyme Inc. A. Wang-Gillam: Advisory / Consultancy: Tyme Inc. S. Pant: Advisory / Consultancy: Tyme Inc. G. Del Priore: Leadership role, Shareholder / Stockholder / Stock options, Full / Part-time employment, Officer / Board of Directors: Tyme Inc. V. Picozzi: Advisory / Consultancy: Tyme Inc. All other authors have declared no conflicts of interest.