Feasibility of SM-88 in PC after multiple prior lines and ECOG < 2.

Abstract

310 Background: Advanced PC patients with ≥ 3Ls of chemo or ECOG PS 2 are generally excluded from clinical trials. SM88 demonstrated no drug related AEs > grade 2 in an interim prostate phase 2 (JCO 2018 36:6S P 175). We sought to determine the feasibility of a trial in this vulnerable population using SM88. Methods: Prospective randomized phase 2 of SM-88 (tyrosine derivative, CYP3a4 inducer, mTOR and oxidative stress catalyst) in patients with locally PD or mPC, ECOG PS < 2 and ≥ 2 weeks from prior therapy. Results: Mean age = 64.9 (range 45.6-84.1); 45.5% female, 93.1% white, 6.9% other; median prior lines = 3 (range 1-6); 12% had prior RT and 17% surgery. Median ECOG PS was 1 with 36.6% 0, 63.3% 1 and 0% ECOG PS 2. From April 2018 to this abstract deadline, 72 patients at 24 sites have consented; 36 patients initiated therapy, 19 failed screening and 17 remained in screening. Time from opening trial to first patient consented = 5.1 wks; median time last regimen to consent = 6.7 wks; from consent to drug administration (C1D1) = 1.7 wks. Subjects traveled up to 2600 miles to enroll at a site with an open slot. Median number of subjects/site = 3 (1-15). Median time on trial is 52 days (1-22 wks). There were 15 unrelated SAEs among 36 randomized subjects; three subjects died after consenting but before receiving study drug (table). Grade 4 and 5 SAEs∗ were more common before receiving drug or unrelated to drug (26/94) than at least possibly drug related (0/17) (Fisher p < 0.05). Efficacy using RECIST, PERCIST and BICR along with CTCs, 19.9, NLR, PROs and other outcomes are being collected with high compliance. Conclusions: This prospective SM88 trial suggests that heavily pretreated PC patients with criteria that includes less than ideal ECOG can participate and gain access to novel therapies. This trial plans to enroll 99 additional subjects in under a year. Although ECOG 2 was allowed none have been consented to date and may reflect investigator bias on enrollment or PS assessment. Investigators can meet the needs of this patient population by considering them for inclusion in future drug development trials. Clinical trial information: NCT03512756. [Table: see text]