LAUSR

200 Background: SM-88 (tyrosine derivative [Td], mTOR inhibitor, CYP3a4 inducer and oxidative stress catalyst) is a relatively non-toxic, targeted therapy that utilizes the Warburg Effect in combination with oxidative stress to cause tumor cell death. It is well suited for pancreas cancer because of its ability to penetrate tumors and be tolerated by debilitated patients. Methods: Patients progressed on at least one line of chemotherapy are eligible for either low versus high dose single agent SM-88 in the dose selecting first stage of this trial. The primary endpoint of the study is response rate by BICR (NCT03512756). Results: As of Sept 23, 36 subjects with initial stage II 26%, III 33%, or IV 41%, were randomized between an active Td dose (430 mg/d) and 920 mg/d. Mean age was 64.9 (45.6 - 84.1); BMI 24.2 (16.8 - 36.7); female 45.5%, white 93.1%, black 4.5%; median of 3 prior lines (range 1 - 6); baseline median albumin, neutrophil lymphocyte ratio, alk phos and 19.9 were 3.8 g/dl (2.6 - 9.6), 4 (1 - 141), 179.5 (54 - 661) and 5089 (4 - 651, 696) respectively. The regimen was well tolerated with no treatment related grade 4 or 5 events; 55.6% of treated subjects (20/36) had 94 AEs, with 18.0% (17/94) being at least possibly treatment related, of which three were grade 3 (arthralgia, fatigue and asthenia). CTCs at baseline were detected in 97% (mean 93.1 cells/4 ml) and fell in 69% (11/16) evaluable subjects from 141.4 to a nadir of 30.7/4 ml (median reduction 77% [3% - 97%]). 22.2% (2/9) evaluable subjects showed CA19.9 declines, both of which also showed CTC declines. 83% of subjects have remained on treatment a median of 4.7 wks (1 - 18.7); 6 were eligible for the initial scheduled assessment at 2 months; 3 of 4 evaluable subjects (75%) had RECIST or PET SUV responses. Lesion SUVs decreased an average of 24.1% (8.3 - 35.7%). EORTC QLQ-C30, -PAN26 and correlative assays were obtained including IGF, leptin, genomics, NLR, and others. Conclusions: SM-88 has demonstrated unconfirmed monotherapy efficacy signals with no meaningful toxicity in a preliminary assessment of this ongoing trial. With additional follow up a dose will be selected for expansion Clinical trial information: NCT03512756.