SM-88 therapy in high risk poor prognosis pancreatic cancer (PDAC)

• Published in: Journal of clinical oncology Vol. 37; no. 15_suppl; p. e15714
• Main Authors: Noel, Marcus Smith, Wang-Gillam, Andrea, Ocean, Allyson J., Chawla, Sant P., Chung, Vincent, Del Priore, Giuseppe, Picozzi, Vincent J.
• Format: Journal Article
• Language: English
• Published: 20.05.2019
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2019.37.15_suppl.e15714

Abstract only e15714 Background: Refractory PDAC has no established therapy (JCO 37, 2019 supp 4; 226). SM-88 (D,L-alpha-metyrosine) is a novel oral therapy used with low doses of sirolimus, phenytoin and methoxsalen. Previous studies show safety and efficacy in compromised patients (JCO 37, 2019 supp 4; 200. JCO 37, 2019 supp 4; 310). We now report the dose optimization phase (NCT03512756). Methods: Randomized Phase 2 with dose optimization and expansion cohort of PDAC after 1 prior line, ECOG PS ≤2 and radiographic PD. Subjects randomized to 460 or 920 mg/d SM-88; all received phenytoin 50 mg, methoxsalen 10 mg and sirolimus 0.5 mg. Results: As of Jan 2019, 85 subjects consented, 41 ineligible, 38 randomized and 28 evaluable (1 cycle dosed). Average age 66.9 yrs, BMI 24.1, CA-19.9 median 2,562 (1.2 – 700,000), 2 prior lines 50%, 3 prior 14.3%, > 4 prior 21.4%; 85.7% had prior 5FU, 89.3% Gem, 71.4% taxanes, and 71.4% platinums. In both SM-88 doses, toxicity did not increase on treatment. AEs were not increased among high risk groups (age, sex, low BMI, low albumin, high CA-19.9 and prior radiotherapy). AEs increased with more prior lines of therapy, but were not dose dependent. There were 21 SAEs prior to dosing including 5 deaths among 14 patients. Two SAEs (rash and hypotension) were considered possibly related to SM-88 Therapy. No deaths were drug-related. 9 subjects had either a CEA or CA-19.9 decrease with 2 having both; 96.5% of subjects had CTCs detectable at baseline with 70% experiencing > 30% decline for at least 1 cycle with a median CTC best response decrease of 73%. Prior Lines of Therapy Subjects (n) Current Median OS 2-month Target Lesion Response CTCs Median Best OR % Alive 1 4 +5.7m 1 PR, 2 SD, 1 n/a* -74% 75% 2 14 +4.7m 6 SD, 3 PD, 5 n/a* -84% 79% 3+ 10 +3.5m 1 PR, 4 PD, 5 n/a* -55% 50% Total 28 +4.3m 2 PR, 8 SD, 7 PD, 11 n/a* -73% 68% *Not available RECIST clinical benefit (SD + PR) was 47.1% (8/17). 68% of subjects were alive at a median follow up of +4.3 months. EORTC global health and QOL measures did not deteriorate on treatment. Conclusions: Both doses of SM-88 were well tolerated without clinically significant toxicity. Anti-tumor activity was observed in this heavily pretreated population warranting expansion of the study for further efficacy evaluation. Clinical trial information: NCT03512756.