Abstract B83: Targeting TRPV6 oncochannel for the treatment of pancreatic cancer: A Phase I trial experience
Authors: Fu Siqing , Welch Stephen , Ilenchuk Toney T. , Dugourd Dominique , Lutes Tyler , Rice Chris , Stewart Jack M. 
Published: December 2016

Abstract
Background: SOR-C13 is a first-in-human selective peptide inhibitor of Transient Receptor Potential Vanilloid 6 (TRPV6) oncochannel. TRPV6 is highly elevated in carcinomas including prostate, breast, lung and ovary and is correlated with poor outcomes. TRPV6-mediated Ca2+ entry is responsible for maintaining a high proliferation rate, increasing cell survival and apoptosis resistance. Since SOR-C13 blocks TRPV6-mediated Ca2+ influx it was evaluated as a single agent in patients with metastatic carcinomas.
Methods: This was a Phase I, multi-center, open-label, dose escalation study to assess safety and tolerability of SOR-C13 in subjects with advanced carcinomas commonly known to express the TRPV6 channel (NCT01578564). Subjects received intravenous infusion of SOR-C13 over 90 minutes for 3 d on/4 d off, 3 d on/11 d off (21 d/cycle) until tumor progression, prohibitive toxicity or patient withdrawal. Tumors were assessed according to RECIST 1.1.
Results: A total of 23 patients were enrolled to 4 dose levels and 119 cycles of therapy were administered. No study drug-related SAEs occurred. Twelve of 22 evaluable subjects (54.5%) had stable disease after 2 cycles. Promising clinical benefit was observed in two patients with advanced metastatic ductal pancreatic cancer. Subject 304 showed stable disease (SD) at dose level of 2.75 mg/kg for 12 weeks, and was removed from the study for persistent grade 2 hepatic transaminase elevation for more than 21 days. Subject 312, treated at dose level of 6.2 mg/kg, showed 7% decrease in tumor size after 2 cycles and a 27% decrease after 4 cycles. Tumor marker CA 19-9 responses were consistent with most changes in tumor size over the treatment cycles with suggestions of a dose related response and correlation with tumor size. The response of this biomarker was particularly evident in the patient initially treated at 6.2 mg/kg where it decreased by 29% after cycle two and by 55% after cycle 4. This patient was removed from the study after a total of 27 weeks 2 days. Both subjects failed at least three prior regimens of anticancer therapy: Subject 304 (i) IMRT/Tomotherapy plus chemoradiation with Folfirinox, (ii) Carboplatin/gemcitabine/Tarceva (iii) Abraxane/Gemcitabine, (iv) IMRT/Tomotherapy; Subject 312 (i) Folfirinox; (ii) gemcitabine and Abraxane; and, (iii) Xeloda.
Conclusions: SOR-C13 was safe and well tolerated in subjects with advanced epithelial malignancies. The clinical benefit observed in patients with metastatic pancreatic cancer, particularly 27% reduction of the sum of tumor diameters after 4 cycles warrants further investigation of this novel treatment in Phase II studies.
Citation Format: Siqing Fu, Stephen Welch, Toney T. Ilenchuk, Dominique Dugourd, Tyler Lutes, Chris Rice, Jack M. Stewart.{Authors}. Targeting TRPV6 oncochannel for the treatment of pancreatic cancer: A Phase I trial experience. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr B83.