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09.01.2019 | PHASE I STUDIES Open Access

A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors

Zeitschrift:
Investigational New Drugs
Autoren:
Toshihiko Doi, Takeshi Aramaki, Hirofumi Yasui, Kei Muro, Masafumi Ikeda, Takuji Okusaka, Yoshitaka Inaba, Kenya Nakai, Hiroki Ikezawa, Ryo Nakajima
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10637-018-0713-7) contains supplementary material, which is available to authorized users.
Some results of this study were previously presented as posters at the European Society for Medical Oncology congress, Madrid, Spain, 26–30 September 2014; and the 51st American Society of Clinical Oncology congress, Chicago, IL, USA, 29 May–2 June 2015.

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Summary

Background We conducted a first-in-Japanese, phase I study of ontuxizumab, a humanized, anti-endosialin monoclonal antibody, to confirm its tolerability, safety, and pharmacokinetics, and identify exploratory efficacy. Methods This was a multicenter, multiple-dose, open-label study in Japanese patients aged ≥20 years with solid tumors, including gastric cancer (GC) or advanced hepatocellular carcinoma (HCC), who had failed standard chemotherapy. The study comprised two parts: part 1 (dose-escalation; ontuxizumab 2–12 mg/kg weekly) and part 2 (cohort-expansion; 4 or 8 mg/kg weekly, or 12 mg/kg biweekly). Results Fifteen patients were treated in part 1, and 31 in part 2 (16 patients with GC and 15 with HCC). In part 1, the most common treatment-related, treatment-emergent adverse event (TEAE) was fatigue (20%); no patients had grade ≥ 3 treatment-related TEAEs. In part 2, the most common treatment-related TEAEs were constipation, malaise, hiccups, and increased bilirubin; treatment-related grade 3 TEAEs occurred in two patients with HCC. In part 1, no patients achieved a partial response, and 6/15 (40%) had stable disease (SD). In part 2, 2/15 patients (13.3%) with GC and 8/15 (53.3%) with HCC had SD. Tumor shrinkage was observed in 5/15 HCC patients (33.3%). Conclusions Ontuxizumab, up to a dosage of 12 mg/kg weekly, was generally safe and well tolerated in this population, with no dose-limiting toxicities. The maximum tolerated dose was not reached; 8 mg/kg weekly or 12 mg/kg biweekly were the recommended dosages. We observed long-term disease stabilization in GC and extraskeletal chondrosarcoma, and tumor shrinkage in gastrointestinal stromal tumor and HCC. Trial registration: NCT01773434 (ClinicalTrials.​gov).

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ESM 1 (DOCX 18 kb)
10637_2018_713_MOESM1_ESM.docx
ESM 2 (DOCX 67 kb)
10637_2018_713_MOESM2_ESM.docx
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