Phase Ib/II safety study of MK615 in combination with gemcitabine + nab-paclitaxel for unresectable/recurrent pancreatic cancer

Abstract Purpose MK615 is a botanical extract derived from Japanese apricot and exhibits anti-inflammatory and antitumor effects in preclinical models. However, its safety in combination with standard cytotoxic chemotherapy has not been clinically evaluated. Methods We conducted a single-arm, open-label, phase Ib/II study to evaluate the safety and tolerability of oral MK615 in combination with gemcitabine and nab-paclitaxel in patients with unresectable or recurrent pancreatic cancer. The primary endpoint was the incidence of dose-limiting toxicities (DLTs) during cycle 1. Secondary endpoints included treatment-emergent adverse events (TEAEs), relative dose intensity (RDI), and exploratory efficacy measures such as objective response rate (ORR), disease control rate (DCR)progression-free survival (PFS), and overall survival (OS). Results All six patients completed phase I without DLTs. For phase II, 23 (including the original six from phase I) were analyzed. The relative dose intensity (RDI) was 94 ± 18% for MK615, 89 ± 14% for gemcitabine, and 82 ± 14% for nab-paclitaxel. Grade ≥ 3 treatment-emergent adverse events were limited to predominantly hematologic toxicity without treatment-related deaths. ORR and DCR were 22% and 74%, respectively, and median OS and PFS were 18.6 and 4.8 months, respectively. Conclusions MK615 in combination with gemcitabine and nab-paclitaxel demonstrated safety and tolerability, with encouraging DCR noted. These results highlight the potential as a complementary therapy in advanced pancreatic cancer, though large-scale studies are needed to confirm efficacy and elucidate the action mechanisms. This study is registered in the Japan Registry of Clinical Trials (jRCTs061180074). Registered on March 20, 2019, retrospectively registered, https://jrct.mhlw.go.jp/latest-detail/jRCTs061180074 .