Abstract CT177: Epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study
Authors: Naing Aung , Powderly John D. , Falchook Gerald , Creelan Benjamin , Nemunaitis John , Lutzky Jose , Diab Adi , Wang Judy S. , Laing Naomi , Niewood Michelle , Gong Xiaohua , Zhou Gongfu , Patel Manish 
Published: August 2018

Abstract
Introduction: Epacadostat, a potent and highly selective oral inhibitor of the indoleamine 2,3- dioxygenase 1 (IDO1) enzyme, plus durvalumab, an anti-PD-L1 antibody, is being studied in patients with advanced solid tumors (NCT02318277). Phase 1 preliminary safety data for the overall population and efficacy data for patients with advanced pancreatic cancer (PC) are reported as of 29 Oct 2017 data cutoff.Methods: Adult patients with PC, melanoma, NSCLC, or SCCHN were enrolled in the 3+3 dose-escalation phase 1. Prior treatment with immune checkpoint inhibitors (in unapproved indications) or IDO inhibitors was not allowed. Patients received epacadostat (25, 50, 75, 100, or 300 mg twice daily [BID]) plus durvalumab (3 or 10 mg/kg every 2 weeks [Q2W]). Safety was assessed in patients receiving ≥1 treatment dose. Response was measured in evaluable patients (≥1 postbaseline scan or discontinued/died before the first scan) per modified RECIST v1.1.Results: Thirty-four patients were enrolled in phase 1. Median age (range) was 68 (46-84) years; most patients were male (62%) and had an ECOG PS of 1 (82%). There was 1 dose-limiting toxicity (grade 3 rash requiring systemic steroids; epacadostat 300 mg BID plus durvalumab 10 mg/kg Q2W) during the 42-day observation period. The most common (≥10%) treatment-related adverse events (TRAEs) were fatigue (32%), pruritus (15%), diarrhea, nausea, and rash (12% each). Grade ≥3 TRAEs occurring in &gt;1 patient included fatigue and rash (n=3 [9%] each). Five patients (15%) discontinued because of TRAEs (grade 1 pneumonitis, grade 2 diarrhea, grade 2 subarachnoid hemorrhage, grade 2 peripheral edema, and grade 3 dyspnea). There were no TRAEs leading to death.Fifteen patients with PC were enrolled across multiple dose levels. Median age (range) was 66 (46-72) years, 67% had liver metastases, and 87% had an ECOG PS of 1. Fourteen patients had received ≥1 prior therapy. PD-L1 expression test results were available in 7/15 patients: 2 had detectable (≥1%) staining of tumor cells; 5 did not. No responses were observed among patients with PC; the disease control rate was 27% (4 SD) per RECIST v1.1 (1 of 4 patients with SD discontinued treatment because of clinical progression). The median duration of disease control was 156 days (95% CI, 91-219).Epacadostat exposure was consistent with previous reports, except in patients with PC where somewhat lower peak exposures (Cmax) were observed.Conclusions: Epacadostat plus durvalumab was generally well tolerated in patients with advanced cancers; the safety profile was consistent with previous reports of durvalumab and epacadostat as monotherapies. In unselected patients with PC, no objective responses were observed; a phase 2 expansion for PC was not conducted. Epacadostat 100 and 300 mg BID are being evaluated in the ongoing phase 2 expansions, including patients with NSCLC, SCCHN, and urothelial carcinoma.
Citation Format: Aung Naing, John D. Powderly, Gerald Falchook, Benjamin Creelan, John Nemunaitis, Jose Lutzky, Adi Diab, Judy S. Wang, Naomi Laing, Michelle Niewood, Xiaohua Gong, Gongfu Zhou, Manish Patel. Epacadostat plus durvalumab in patients with advanced solid tumors: preliminary results of the ongoing, open-label, phase I/II ECHO-203 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT177.