Efficacy and safety of TAS-115, a novel oral multi-kinase inhibitor, in osteosarcoma: an expansion cohort of a phase I study

Investigational New Drugs - 2021
Akira Kawai1, Norifumi Naka2, Akihiko Shimomura3,4, Shunji Takahashi5, Shigehisa Kitano6,7,8, Yoshinori Imura2, Kan Yonemori4, Fumihiko Nakatani1, Shintaro Iwata1, Eisuke Kobayashi1, Hidetatsu Outani9, Hironari Tamiya2, Yoichi Naito10, Noboru Yamamoto8, Toshihiko Doi11
1Department of Musculoskeletal Oncology and Rehabilitation, National Cancer Center Hospital, Tokyo, Japan
2Musculoskeletal Oncology Service, Osaka International Cancer Institute, Osaka, Japan
3Department of Breast and Medical Oncology, National Center for Global Health and Medicine, Tokyo, Japan
4Department of Breast and Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
5Department of Medical Oncology, The Cancer Institute Hospital of JFCR, Tokyo, Japan
6Present address: Division of Cancer Immunotherapy Development, The Cancer Institute Hospital of JFCR, Tokyo, Japan
7Present address: Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan
8Experimental Therapeutics, National Cancer Center Hospital, Tokyo, Japan
9Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
10Department of Experimental Therapeutics/Breast and Medical Oncology, National Cancer Center Hospital East, Kashiwa, Japan
11Department of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa, Japan

Tóm tắt

Background osteosarcoma is a rare, primary malignant bone tumour with limited available treatments for advanced or recurrent disease, resulting in a poor prognosis for patients. TAS-115 is a novel tyrosine kinase inhibitor under investigation in a phase I study in patients with solid tumours. We report data of osteosarcoma patients in the expansion cohort of this ongoing study. Patients and methods an analysis of this multicentre, open-label study was performed 6 months after the final patient was enrolled, and included patients aged ≥15 years, with unresectable or recurrent osteosarcoma, and who had refractory to standard therapy or for whom no standard therapy was available. TAS-115 650 mg/day was orally administered in a 5 days on/2 days off schedule. Results a total of 20 patients with osteosarcoma were enrolled. The most common adverse drug reactions (ADRs) were neutrophil count decreased (75%), aspartate aminotransferase increased (50%), and platelet count decreased (50%); 85% of patients had grade ≥ 3 ADRs. Long-term disease control (>1 year) with TAS-115 was achieved in three patients. The best overall response was stable disease (50%); no patient achieved a complete or partial response. Median progression-free survival was 3 months; 4-month and 12-month progression-free rates were 42% and 31%, respectively. Conclusion the safety and tolerability of TAS-115 and long-term disease stability for patients with unresectable or recurrent osteosarcoma were confirmed in this study, suggesting that TAS-115 is a promising novel therapy for advanced osteosarcoma patients. Trial registration number: JapicCTI-132333 (registered on November 8, 2013).

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