Abstract B16: CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer
Authors: Noel Marcus Smith , Wang-Gillam Andrea , Ocean Allyson J. , Chawla Sant , Chung Vincent , Korn Ron , Priore Giuseppe Del , Picozzi Vincent J. 
Published: March 2020

Abstract
Background: Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis, with 80% of patients succumbing within the first year and only 8% surviving &gt;5 years. Responses are rare in later-line, metastatic PDAC trials. Thus, there is a clear unmet need to develop new treatment approaches guided by new and more accurate efficacy markers correlating with overall survival (OS) and not classical RECIST. SM-88 (racemetryrosine) used with methoxsalen, phenytoin, and sirolimus (MPS) has demonstrated effective reduction in circulating tumor cells (CTCs) in prostate and PDAC using multiple CTC assay variations. We now report OS associations.
Method: Randomized phase II, multicenter, open-label prospective trial evaluating SM-88 in advanced PDAC. Ninety-nine patients were screened; 49 met inclusion criteria, with 38 evaluable per protocol. The trial evaluated overall survival, CTCs, PK parameters, and RECIST-determined response. Additional metabolism-related measures hypothesized to be impacted by SM-88s were also investigated (leptin, NLR, glucose, and others). CTCs were measured using a next-generation, microfluidic magnetic-based antibody detection method.
Results: Preliminary results showed multiple efficacy measures correlated with overall survival. At baseline, in all evaluable patients (n=38, mean age 66yrs, approximately 80% having &gt;2 prior lines) median CTCs were 110.8 CTCs/4mL, whereas those who achieved stable disease (SD) (n=4) and whose CTC levels decreased on SM-88 reported 123.2 CTCs/4mL at baseline. However, one patient who was a CTC responder and achieved a partial response (PR) had 13.3 CTCs/4mL at baseline. Patients with both an absolute and percent decrease from baseline in CTCs demonstrated greater OS using multiple threshold reductions; patients with &gt;80% decrease or reduction in cell count to &lt;50 CTCs/4mL demonstrated the strongest correlation with extended survival (p=0.18). Higher SM-88 Cmax (p=0.07) and AUC-6 (p&lt;0.001) also correlated with OS. Based on RECIST, the clinical benefit rate (stable disease [SD] plus partial response [PR]) was 44%. There was a demonstrated survival advantage for patients who achieved SD (p&lt;0.02). Females also achieved greater OS (p=0.01), which suggests the need for further clinical investigation. Metabolic measures of glucose levels (p=0.46) and leptin (p=0.28) did not appear to differ by sex.
Conclusion: These data for SM-88 in PDAC illustrate that there are clear efficacy correlates with overall survival beyond traditional RECIST responses, including CTC measures. This may be of translational significance as the association between decreases in CTCs and overall survival had not been previously well documented prospectively in PDAC as compared to other tumor types. All together, these data are encouraging and warrant additional clinical investigation aimed at improving the dismal outcome of this malignancy.
Citation Format: Marcus Smith Noel, Andrea Wang-Gillam, Allyson J. Ocean, Sant Chawla, Vincent Chung, Ron Korn, Giuseppe Del Priore, Vincent J. Picozzi. CTC-based efficacy of SM-88 correlates with overall survival in advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B16.