A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors
| العنوان: | A phase I study of ontuxizumab, a humanized monoclonal antibody targeting endosialin, in Japanese patients with solid tumors |
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| المؤلفون: | Kenya Nakai, Hirofumi Yasui, Yoshitaka Inaba, Kei Muro, Takuji Okusaka, Masafumi Ikeda, Hiroki Ikezawa, Toshihiko Doi, Takeshi Aramaki, Ryo Nakajima |
| المصدر: | Investigational New Drugs |
| بيانات النشر: | Springer Science and Business Media LLC, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Monoclonal antibody, Male, 0301 basic medicine, medicine.medical_specialty, Maximum Tolerated Dose, medicine.medical_treatment, Population, Antineoplastic Agents, Antibodies, Monoclonal, Humanized, Gastroenterology, Cohort Studies, 03 medical and health sciences, Phase I, 0302 clinical medicine, Japan, Pharmacokinetics, Antigens, CD, Antigens, Neoplasm, Phase I Studies, Neoplasms, Internal medicine, Humans, Medicine, Tissue Distribution, Pharmacology (medical), Stromal tumor, education, Adverse effect, Aged, Pharmacology, education.field_of_study, Chemotherapy, business.industry, Cancer, Endosialin, Middle Aged, Prognosis, medicine.disease, CD248 antigen inhibitor, 030104 developmental biology, Ontuxizumab, Oncology, Tolerability, 030220 oncology & carcinogenesis, Hepatocellular carcinoma, Female, Neoplasm Recurrence, Local, business, Follow-Up Studies |
| الوصف: | 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). |
| تدمد: | 1573-0646 0167-6997 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bf6ea021b6eed80e390c3ccaebde41aTest https://doi.org/10.1007/s10637-018-0713-7Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1bf6ea021b6eed80e390c3ccaebde41a |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15730646 01676997 |
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