PD‐1 inhibition with retifanlimab and/or arginase inhibition with INCB001158 in Japanese patients with solid tumors: A phase I study

• Published in: Cancer medicine (Malden, MA) MA), 2024-04, Vol.13 (8), p.e6980-n/a
• Main Authors: Kuboki, Yasutoshi, Koyama, Takafumi, Matsubara, Nobuaki, Naito, Yoichi, Kondo, Shunsuke, Harano, Kenichi, Yonemori, Kan, Yoh, Kiyotaka, Gu, Yuan, Mita, Tetsuya, Chen, Xuejun, Ueda, Eiji, Yamamoto, Noboru, Doi, Toshihiko, Shimizu, Toshio
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Antitumor activity; Arginase; Arginase - antagonists & inhibitors; Cancer therapies; Chemotherapy; Disease control; Drug dosages; East Asian People; Endometrial cancer; Female; Granulocytes; Humans; Immune Checkpoint Inhibitors - adverse effects; Immune Checkpoint Inhibitors - therapeutic use; Immunoassay; Immunotherapy; Japan; Ligands; Male; Metastasis; Middle Aged; Monoclonal antibodies; Neoplasms - drug therapy; PD-1 protein; PD‐1 inhibitor; Pharmacokinetics; Plasma; Programmed Cell Death 1 Receptor - antagonists & inhibitors; retifanlimab; Solid tumors; Toxicity; Tumors
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.6980

Background Retifanlimab is a humanized monoclonal antibody targeting programmed death protein‐1, and INCB001158 is an oral arginase inhibitor. This phase Ib study investigated retifanlimab, INCB001158, and their combination in Japanese patients with advanced solid tumors. Methods Patients received retifanlimab (500 mg every 4 weeks [Q4W] i.v.) or escalating doses of INCB001158 (75 or 100 mg twice daily [BID]) monotherapy in Part 1 and combination of retifanlimab (500 mg Q4W) and INCB001158 (100 mg BID) in Part 2. Primary endpoints were safety, tolerability, dose‐limiting toxicities (DLTs), and determination of recommended phase II doses in Japanese patients. Results Eighteen patients (retifanlimab or INCB001158 monotherapy and combination; n = 6 each) were enrolled at 2 sites in Japan. There were no DLTs, fatal adverse events (AEs), or discontinuations due to AEs. Rash (all grade 1) was the most common treatment‐emergent AE with retifanlimab (n = 6). Treatment‐related AEs were reported with retifanlimab (n = 4) or INCB001158 (n = 2) monotherapy and with combination (n = 4); an immune‐related AE (thyroid disorder, grade 2) was reported with combination. Two responses were observed with retifanlimab monotherapy (1 complete, 1 partial) and 1 stable disease (SD), for an overall response rate of 33.3% (95% confidence interval [CI], 4.3–77.7) and disease control rate (DCR) of 50% (95% CI, 11.8–88.2). Three patients had SD with INCB001158 monotherapy (DCR 50%; 95% CI, 11.8–88.2). No responses or SD were observed with combination therapy. Conclusion Retifanlimab, INCB001158, and their combination had acceptable safety profiles. Promising retifanlimab antitumor activity warrants further investigation in Japanese patients. POD1UM‐104 evaluated the safety, tolerability, dose‐limiting toxicities (DLTs), and recommended phase II dose (RP2D) of retifanlimab (PD‐1 inhibitor, A), INCB001158 (arginase inhibitor, B), and their combination (retifanlimab + INCB001158, C) in Japanese patients with advanced solid tumors. There were no DLTs and no adverse events with fatal outcomes or leading to treatment discontinuation reported; the overall response rate was 33.3% and disease control rate was 50.0% with retifanlimab monotherapy. At the RP2D of 500 mg administered every 4 weeks, retifanlimab had a manageable safety profile and demonstrated encouraging antitumor activity, supporting further evaluation in Japanese patients.