Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma

Kazuhiko Nakagawa, MD, PhD; Takashi Kijima, MD, PhD; Morihito Okada, MD, PhD; Masahiro Morise, MD, PhD; Motoyasu Kato, MD, PhD; Katsuya Hirano, MD; Nobukazu Fujimoto, MD, PhD; Mitsuhiro Takenoyama, MD, PhD; Hiroshi Yokouchi, MD, PhD; Yuichiro Ohe, MD, PhD; Toyoaki Hida, MD, PhD; Keisuke Aoe, MD, PhD; Takumi Kishimoto, MD, PhD; Masato Hirokawa, MSc; Hironori Matsuki, MEng; Yutaro Kaneko, BSc; Taketo Yamada, MD, PhD; Chikao Morimoto, MD, PhD; Masayuki Takeda, MD, PhD

JTO Clinical and Research Reports (Jun 2021)

Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma

Kazuhiko Nakagawa, MD, PhD,
Takashi Kijima, MD, PhD,
Morihito Okada, MD, PhD,
Masahiro Morise, MD, PhD,
Motoyasu Kato, MD, PhD,
Katsuya Hirano, MD,
Nobukazu Fujimoto, MD, PhD,
Mitsuhiro Takenoyama, MD, PhD,
Hiroshi Yokouchi, MD, PhD,
Yuichiro Ohe, MD, PhD,
Toyoaki Hida, MD, PhD,
Keisuke Aoe, MD, PhD,
Takumi Kishimoto, MD, PhD,
Masato Hirokawa, MSc,
Hironori Matsuki, MEng,
Yutaro Kaneko, BSc,
Taketo Yamada, MD, PhD,
Chikao Morimoto, MD, PhD,
Masayuki Takeda, MD, PhD

Affiliations

Kazuhiko Nakagawa, MD, PhD: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan; Corresponding author, Address for correspondence: Kazuhiko Nakagawa, MD, PhD, Department of Medical Oncology, Kindai University Faculty of Medicine, 377-2 Ohno-higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Takashi Kijima, MD, PhD: Department of Respiratory Medicine and Hematology, Hyogo College of Medicine, Nishinomiya City, Japan
Morihito Okada, MD, PhD: Department of Surgical Oncology, Hiroshima University, Hiroshima City, Japan
Masahiro Morise, MD, PhD: Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya City, Japan
Motoyasu Kato, MD, PhD: Department of Respiratory Medicine, Juntendo University Graduate School of Medicine, Tokyo, Japan
Katsuya Hirano, MD: Department of Respiratory Medicine, Hyogo Prefectural Amagasaki General Medical Center, Amagasaki City, Japan
Nobukazu Fujimoto, MD, PhD: Department of Medical Oncology, Okayama Rosai Hospital, Okayama City, Japan
Mitsuhiro Takenoyama, MD, PhD: Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka City, Japan
Hiroshi Yokouchi, MD, PhD: Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, Sapporo City, Japan
Yuichiro Ohe, MD, PhD: Department of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
Toyoaki Hida, MD, PhD: Department of Thoracic Oncology, Aichi Cancer Center Hospital, Nagoya City, Japan
Keisuke Aoe, MD, PhD: Department of Medical Oncology, National Hospital Organization Yamaguchi-Ube Medical Center, Ube City, Japan
Takumi Kishimoto, MD, PhD: Research & Training Center for Asbestos-Related Diseases, Okayama City, Japan
Masato Hirokawa, MSc: Kissei Pharmaceutical Co. Ltd., Tokyo, Japan
Hironori Matsuki, MEng: Kissei Pharmaceutical Co. Ltd., Tokyo, Japan
Yutaro Kaneko, BSc: Y’s AC Co. Ltd., Tokyo, Japan
Taketo Yamada, MD, PhD: Department of Pathology, Saitama Medical University, Iruma-gun, Japan
Chikao Morimoto, MD, PhD: Department of Therapy Development and Innovation for Immune Disorders and Cancers, Graduate School of Medicine, Juntendo University, Tokyo, Japan
Masayuki Takeda, MD, PhD: Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka-Sayama, Japan

Journal volume & issue: Vol. 2, no. 6
p. 100178

Abstract

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Introduction: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study. Methods: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest). Results: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab—groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths. Conclusions: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

Published in JTO Clinical and Research Reports

ISSN: 2666-3643 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Internal medicine: Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Website: https://www.journals.elsevier.com/jto-clinical-and-research-reports/

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