مورد إلكتروني
Phase 1/2a trial of BMS-986148, an anti-mesothelin antibody-drug conjugate, alone or in combination with nivolumab in patients with advanced solid tumors.
| العنوان: | Phase 1/2a trial of BMS-986148, an anti-mesothelin antibody-drug conjugate, alone or in combination with nivolumab in patients with advanced solid tumors. |
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| المؤلفون: | Rottey S., Clarke J., Aung K., Machiels J.-P., Markman B., Heinhuis K.M., Millward M., Lolkema M., Patel S.P., de Souza P., Duca M., Curigliano G., Santoro A., Koyama T., Brown M., Vezina H., He C., Chu Q.S.-C. |
| بيانات النشر: | NLM (Medline) United States 2021-10-30 |
| نوع الوثيقة: | Electronic Resource |
| مستخلص: | PURPOSE: To assess the safety and tolerability of BMS-986148, a mesothelin-directed antibody-drug conjugate (ADC) {plus minus} nivolumab in patients with selected tumors. EXPERIMENTAL DESIGN: In an international phase 1/2a study (NCT02341625 [CA008-002]), patients received BMS-986148 monotherapy (0.1-1.6 mg/kg IV Q3W or 0.4 or 0.6 mg/kg IV QW; n = 96) or BMS-986148 0.8 mg/kg + nivolumab 360 mg IV Q3W (n = 30). The primary endpoint was safety and tolerability. RESULT(S): In CA008-002, the most common ({greater than or equal to} 10%) treatment-related adverse events (TRAEs) included increased AST, ALT, and ALP. Grade 3/4 TRAEs occurred in 42 patients (49%) receiving BMS-986148 Q3W monotherapy, 3 (25%) receiving BMS-986148 QW monotherapy, and 10 (33%) receiving BMS-986148 + nivolumab Q3W. Overall, 17 of 126 patients (13%) discontinued due to a TRAE. The maximum tolerated dose of BMS-986148 was 1.2 mg/kg IV Q3W.The safety profile of BMS-986148 + nivolumab was similar to that of BMS-986148 monotherapy (0.8 mg/kg). Active ADC exposures increased in a dose-proportional manner with both dosing regimens (Q3W and QW). Preliminary clinical activity was observed with BMS-986148 {plus minus} nivolumab. No association between mesothelin expression and response was detected. CONCLUSION(S): BMS-986148 {plus minus} nivolumab demonstrated a clinically manageable safety profile and preliminary evidence of clinical activity, supporting additional studies combining directed cytotoxic therapies with checkpoint inhibitors as potential multimodal therapeutic strategies in patients with advanced solid tumors. |
| مصطلحات الفهرس: | Article |
| URL: | Clinical Cancer Research: An Official Journal of the American Association for Cancer Research LibKey Link |
| الإتاحة: | Open access content. Open access content |
| أرقام أخرى: | AUSHL oai:repository.monashhealth.org:1/45891 Clinical cancer research : an official journal of the American Association for Cancer Research. (no pagination), 2021. Date of Publication: 06 Oct 2021. https://repository.monashhealth.org/monashhealthjspui/handle/1/45891 34615718 [http://www.ncbi.nlm.nih.gov/pubmed/?term=34615718] (Markman) Oncology, Monash Medical Centre (Rottey) Department of Medical Oncology, Ghent University Hospital - 4B11 (Clarke) Medicine, Duke Medical Center (Aung) Medical Oncology and Hematology, Princess Margaret Cancer Centre (Machiels) Department of medical oncology and head and neck surgery, Cancer center, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Experimentale (Pole MIRO), Universite catholique de Louvain, Brussels, Belgium (Heinhuis) Netherlands Cancer Institute, Amsterdam, United States (Millward) Linear Clinical Research, University of Western Australia (Lolkema) Department of Medical Oncology, Erasmus MC Cancer Institute (Patel) Medicine, UC San Diego Moores Cancer Center (de Souza) School of Medicine, Western Sydney University (Duca) Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale dei Tumori (Curigliano) Department of Oncology and Hemato-Oncology, University of Milano, European Institute of Oncology, IRCCS, Milano, Italy (Santoro) Department of Oncology and Hematology, IRCCS Humanitas Research Hospital (Koyama) Department of Experimental Therapeutics, National Cancer Center Hospital (Brown, He) Bristol-Myers Squibb (United States) (Vezina) Clinical Pharmacology and Pharmacometrics, Bristol-Meyers Squibb (Chu) Medical Oncology, Cross Cancer Institute, University of Alberta (Rottey) Department of Medical Oncology, Ghent University Hospital - 4B11 (Clarke) Medicine, Duke Medical Center (Aung) Medical Oncology and Hematology, Princess Margaret Cancer Centre (Machiels) Department of medical oncology and head and neck surgery, Cancer center, Cliniques universitaires Saint-Luc and Institut de Recherche Clinique et Experimentale (Pole MIRO), Universite catholique de Louvain, Brussels, Belgium (Heinhuis) Netherlands Cancer Institute, Amsterdam, United States (Millward) Linear Clinical Research, University of Western Australia (Lolkema) Department of Medical Oncology, Erasmus MC Cancer Institute (Patel) Medicine, UC San Diego Moores Cancer Center (de Souza) School of Medicine, Western Sydney University (Duca) Oncologia Medica 1, Fondazione IRCCS Istituto Nazionale dei Tumori (Curigliano) Department of Oncology and Hemato-Oncology, University of Milano, European Institute of Oncology, IRCCS, Milano, Italy (Santoro) Department of Oncology and Hematology, IRCCS Humanitas Research Hospital (Koyama) Department of Experimental Therapeutics, National Cancer Center Hospital (Brown, He) Bristol-Myers Squibb (United States) (Vezina) Clinical Pharmacology and Pharmacometrics, Bristol-Meyers Squibb (Chu) Medical Oncology, Cross Cancer Institute, University of Alberta (Markman) Oncology, Monash Medical Centre 1305137285 |
| المصدر المساهم: | MONASH HEALTH LIBRS From OAIster®, provided by the OCLC Cooperative. |
| رقم الأكسشن: | edsoai.on1305137285 |
| قاعدة البيانات: | OAIster |
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