Background: INCB024360 (epacadostat) is an oral, potent, selective inhibitor of indoleamine 2,3-dioxygenase 1 (IDO1), a tryptophan-catabolizing enzyme that induces immune tolerance by T-cell suppression. Preliminary results from the phase I study of INCB024360 with pembrolizumab, an anti-PD-1 monoclonal antibody, exhibited an acceptable safety profile and promising clinical activities. This first-in-Japanese phase 1 study assessed the safety and the tolerability of INCB024360 monotherapy and in combination with pembrolizumab in Japanese patients with advanced solid tumors ( NCT02862457). Materials and Methods: Patients with advanced solid tumors who had previously received standard-of-care were enrolled; patients previously treated with checkpoint inhibitors were excluded. Patients received INCB024360 25 mg or 100 mg BID monotherapy, or in combination with intravenous pembrolizumab 200 mg every 3 weeks (Q3W). Dose-limiting toxicities (DLTs) were evaluated for INCB024360 monotherapy and in combination with pembrolizumab. Response rate was also assessed by RECIST 1.1. Patients who had INCB024360 monotherapy subsequently received pembrolizumab combination after DLT evaluation. Results: Fifteen patients were enrolled (53% men; median age, 68.0 y; 33% ECOG PS 1): urothelial cancer, colon cancer, gastric cancer, ovarian cancer, urachal cancer, and cancer of unknown primary (n=2, each); duodenal papilla cancer, mesothelioma, and pancreatic cancer (n=1, each). Three patients each received 25 mg and 100 mg of INCB024360 monotherapy, showed no DLTs. In combination with pembrolizumab, three and six patients received INCB024360 dose of 25 mg and 100 mg, respectively. One DLT (grade 4, rhabdomyolysis) was observed in 100 mg cohort. Twelve patients (80.0%) experienced drug-related AEs (DRAEs); 2 patients (13.3%) had grade 3 DRAEs: grade 3 liver disorder and grade 4 rhabdomyolysis. There were no treatment-related deaths. In 15 patients who had target lesion, partial responses were observed in 4 patients (26.7%) and stable disease were 4 (26.7%). As of 2 June 2017, all responders with pancreatic cancer, urothelial cancer, colon cancer with MSI-high and cancer of unknown primary (n=1, each) remain on treatment at 21, 24, 31, and 34 weeks, respectively. Conclusion: INCB024360 monotherapy and in combination with pembrolizumab demonstrated tolerability and encouraging efficacy in the Japanese patients with advanced solid tumors. Latest safety as well as efficacy data will be presented.

Citation Format: Yutaka Fujiwara, Kohei Shitara, Toshio Shimizu, Kan Yonemori, Nobuaki Matsubara, Izumi Ohno, Takahiro Kogawa, Yoichi Naito, Lance Leopold, Kahori Sasahara, Naoyoshi Yatsuzuka, Tomoko Takami, Takashi Shimamoto, Noboru Yamamoto, Toshihiko Doi. INCB024360 (Epacadostat) monotherapy and in combination with pembrolizumab in patients with advanced solid tumors: primary results from first-in-Japanese phase I study (KEYNOTE-434) [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A204.