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1528P Phase I trial of the first-in-class agent CEND-1 in combination with gemcitabine and nab-paclitaxel in patients with metastatic pancreatic cancer

      Background

      CEND-1 is a bifunctional cyclic peptide (a.k.a. iRGD) that, based on experimental models, homes to tumors via RGD motif interaction with alphav-integrins and then transforms the solid tumor microenvironment into a temporary drug conduit via interaction with neuropilin-1. This leads to an enhanced tumor delivery of co-administered anti-cancer agents. The physical barrier to drug entry is especially prominent in pancreatic cancer and was therefore chosen as the first clinical indication for CEND-1.

      Methods

      The open-label, multicenter (3 active sites) trial involved a run-in phase with CEND-1 monotherapy (1-7 days), followed by a combination of CEND-1 with nab-paclitaxel (125 mg/m2) and gemcitabine (1000 mg/m2) on days 1, 8, 15 of a 21-day treatment cycle. Patients who had measurable metastatic pancreatic cancer, no prior treatments for metastatic disease and an ECOG PS of 0 to 1 were included. Primary endpoints are safety and optimal biologic dose, secondary endpoints included overall response rate.

      Results

      29 patients completed the first treatment cycle and were evaluable for response. No dose limiting toxicities were observed. AEs were generally consistent with those of nabpaclitaxel and gemcitabine. The only drug related grade (gr) 3 - 4 adverse events (AEs) present in ≥3 patients were neutropenia in 19 (66%), anemia in 8 (28%) and peripheral neuropathy in 4 (14%) patients. By investigator assessed RECIST 1.1 criteria, the overall response rate was 59%, one pt. with complete response (3.4%), 16 pts. with partial response (55%), 10 pts. with stable disease (34%), and 2 pts. with progressive disease (6.9%). The Disease Control Rate for 16 weeks (DCR) was 83%. Among the patients with elevated CA19-9 and a postbaseline assessment, a total of 95% of the patients had a decrease from baseline of at least 20%, and 77% had a decrease of at least 90% and/or had the CA19-9 levels normalized to baseline.

      Conclusions

      Administration of CEND-1 in combination with nab-paclitaxel and gemcitabine is safe, with encouraging efficacy profile. Confirmatory randomized trials are warranted.

      Clinical trial identification

      NCT03517176.

      Legal entity responsible for the study

      DrugCendR Australia Pty Ltd.

      Funding

      DrugCendR Australia Pty Ltd.

      Disclosure

      H.A. Jarvelainen: Full/Part-time employment: Cend Therapeutics Inc.; Officer/Board of Directors: DrugCendR Australia Pty Ltd. T.J. Price: Full/Part-time employment: Cend Therapeutics Inc. All other authors have declared no conflicts of interest.