Journal article
The safety and tolerability of epacadostat alone and in combination with pembrolizumab in patients with advanced solid tumors: results from a first-in-Japanese phase I study (KEYNOTE-434)
Investigational new drugs, v 39(1), pp 152-162
01 Feb 2021
PMID: 32564277
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Part A of the open-label, phase I KEYNOTE-434 study evaluated the safety and tolerability of epacadostat, an indoleamine 2,3-dioxygenase-1 inhibitor, alone and in combination with pembrolizumab in Japanese patients with advanced solid tumors.
Japanese patients with refractory/recurrent metastatic or locally advanced tumors were enrolled. Cohort 1 received oral epacadostat 25 mg or 100 mg twice daily (BID) and subsequently received epacadostat in combination with intravenous pembrolizumab 200 mg every 3 weeks. Cohort 2 received epacadostat 25 mg or 100 mg BID with pembrolizumab 200 mg every 3 weeks. The primary objective was evaluation of safety and tolerability using a modified toxicity probability interval method. Secondary objectives were pharmacokinetic (PK) and pharmacodynamic profiles of epacadostat alone and in combination with pembrolizumab.
Six patients were enrolled in cohort 1 (epacadostat 25 mg, n = 3; epacadostat 100 mg, n = 3); none experienced dose-limiting toxicities (DLTs). Nine patients were enrolled in cohort 2 (epacadostat 25 mg and pembrolizumab, n = 3; epacadostat 100 mg and pembrolizumab, n = 6); one patient receiving epacadostat 100 mg and pembrolizumab experienced grade 4 rhabdomyolysis-a DLT. Grade 3 or 4 treatment-related adverse events occurred in two patients (13.3%). There were no treatment-related deaths. Pembrolizumab had no impact on epacadostat PK and vice versa. The PK profile of pembrolizumab in the current study was comparable with historical pembrolizumab PK data.
Epacadostat in combination with pembrolizumab was generally safe and well tolerated among Japanese patients with advanced solid tumors. Clinical trial registration NCT02862457.
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Details
- Title
- The safety and tolerability of epacadostat alone and in combination with pembrolizumab in patients with advanced solid tumors: results from a first-in-Japanese phase I study (KEYNOTE-434)
- Creators
- Toshihiko Doi - National Cancer Center Hospital EastYutaka Fujiwara - Mitsui Memorial HospitalKohei Shitara - National Cancer Center Hospital EastToshio Shimizu - Tokyo National HospitalKan Yonemori - Tokyo National HospitalNobuaki Matsubara - National Cancer Center Hospital EastIzumi Ohno - National Cancer Center Hospital EastTakahiro Kogawa - National Cancer Center Hospital EastYoichi Naito - National Cancer Center Hospital EastLance Leopold - Incyte (United States)Mihaela Munteanu - Incyte (United States)Naoyoshi Yatsuzuka - MSD K.K. (Japan)Shi Rong Han - MSD K.K. (Japan)Ayman Samkari - MSD (Mexico)Noboru Yamamoto - Tokyo National Hospital
- Publication Details
- Investigational new drugs, v 39(1), pp 152-162
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000541386400001
- Scopus ID
- 2-s2.0-85086745731
- Other Identifier
- 991021838136204721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology
- Pharmacology & Pharmacy