A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma
| العنوان: | A phase 1 trial of SGN-CD70A in patients with CD70-positive diffuse large B cell lymphoma and mantle cell lymphoma |
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| المؤلفون: | Hong Li, David Smith, Thomas E. Boyd, Paul M. Barr, Cindy Yu, Anne Sophie Carret, Steven I. Park, Robert T. Chen, Kathryn S. Kolibaba, Saurabh Chhabra, Tycel Phillips, Edwin C. Kingsley, Paolo Caimi, Elaina M. Gartner |
| المصدر: | Investigational New Drugs |
| بيانات النشر: | Springer US, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Immunoconjugates, CD70 antigen, Lymphoma, Mantle-Cell, Gastroenterology, Benzodiazepines, 0302 clinical medicine, hemic and lymphatic diseases, Phase I Studies, Grade 3b Follicular Lymphoma, Pyrrolobenzodiazepine dimer (PBD), Pharmacology (medical), Tissue Distribution, Aged, 80 and over, Antibodies, Monoclonal, Diffuse, large B cell, lymphoma (DLBCL), Middle Aged, Prognosis, Gene Expression Regulation, Neoplastic, Mantle-cell lymphoma, Oncology, 030220 oncology & carcinogenesis, Female, Lymphoma, Large B-Cell, Diffuse, medicine.symptom, Adult, medicine.medical_specialty, Lymphoma, B-Cell, Maximum Tolerated Dose, Anemia, Nausea, 03 medical and health sciences, Refractory, Internal medicine, medicine, Biomarkers, Tumor, Humans, Pyrroles, Adverse effect, Antibody-drug conjugate, Aged, Pharmacology, Salvage Therapy, business.industry, medicine.disease, Grade 3 follicular lymphoma, Lymphoma, 030104 developmental biology, Drug Resistance, Neoplasm, Mantle cell lymphoma, Neoplasm Recurrence, Local, business, Diffuse large B-cell lymphoma, CD27 Ligand, Follow-Up Studies |
| الوصف: | Summary Purpose This first-in-human study evaluated SGN-CD70A, an antibody-drug conjugate (ADC) directed against the integral plasma membrane protein CD70 and linked to a pyrrolobenzodiazepine (PBD) dimer, in patients with relapsed or refractory (R/R) CD70-positive non-Hodgkin lymphoma (NHL) including diffuse large B cell lymphoma (DLBCL), mantle cell lymphoma (MCL), and Grade 3b follicular lymphoma (FL3b). Methods SGN-CD70A was administered intravenously on Day 1 of 3-week cycles beginning at 8 mcg/kg with planned dose escalation to 200 mcg/kg. Due to observations of prolonged thrombocytopenia, the study was amended to dose every 6 weeks (q6wk). Results Twenty patients were enrolled and treated with SGN-CD70A. The maximum tolerated dose of SGN-CD70A was 30 mcg/kg q6wk. The most common adverse events (AEs) reported were thrombocytopenia (75%), nausea (55%), anemia (50%), and fatigue (50%). The onset for treatment-related thrombocytopenia typically occurred during Cycle 1. Most of the treatment-related events of thrombocytopenia were ≥ Grade 3. Antitumor activity in patients included 1 complete remission (CR) and 3 partial remissions (PRs), 2 of which were ongoing for at least 42.9 weeks. SGN-CD70A exposures were approximately dose proportional, with a mean terminal half-life of 3 to 5 days. Conclusions While modest single-agent activity was observed in heavily pretreated NHL patients, the applicability of SGN-CD70A is limited by the frequency and severity of thrombocytopenia, despite the long-term response with limited drug exposure. Electronic supplementary material The online version of this article (10.1007/s10637-018-0655-0) contains supplementary material, which is available to authorized users. |
| اللغة: | English |
| تدمد: | 1573-0646 0167-6997 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b4e977ba1b77526f3582de9b9ef2df5cTest http://europepmc.org/articles/PMC6440937Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....b4e977ba1b77526f3582de9b9ef2df5c |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15730646 01676997 |
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