التفاصيل البيبلوغرافية
| العنوان: |
First-in-human phase 1 clinical trial of anti-core 1 O-glycans targeting monoclonal antibody NEO-201 in treatment-refractory solid tumors |
| المؤلفون: |
Cole, Christopher B., Morelli, Maria Pia, Fantini, Massimo, Miettinen, Markku, Fetsch, Patricia, Peer, Cody, Figg, William D., Yin, Tyler, Houston, Nicole, McCoy, Ann, Lipkowitz, Stanley, Zimmer, Alexandra, Lee, Jung-min, Pavelova, Miroslava, Villanueva, Erin N., Trewhitt, Kathryn, Solarz, B. Brooke, Fergusson, Maria, Mavroukakis, Sharon A., Zaki, Anjum, Tsang, Kwong Y., Arlen, Philip M., Annunziata, Christina M. |
| المساهمون: |
Precision Biologics, Inc, National Cancer Institute |
| المصدر: |
Journal of Experimental & Clinical Cancer Research ; volume 42, issue 1 ; ISSN 1756-9966 |
| بيانات النشر: |
Springer Science and Business Media LLC |
| سنة النشر: |
2023 |
| مصطلحات موضوعية: |
Cancer Research, Oncology |
| الوصف: |
Background NEO201 is a humanized IgG1 monoclonal antibody (mAb) generated against tumor-associated antigens from patients with colorectal cancer. NEO-201 binds to core 1 or extended core 1 O-glycans expressed by its target cells. Here, we present outcomes from a phase I trial of NEO-201 in patients with advanced solid tumors that have not responded to standard treatments. Methods This was a single site, open label 3 + 3 dose escalation clinical trial. NEO-201 was administered intravenously every two weeks in a 28-day cycle at dose level (DL) 1 (1 mg/kg), DL 1.5 (1.5 mg/kg) and DL 2 (2 mg/kg) until dose limiting toxicity (DLT), disease progression, or patient withdrawal. Disease evaluations were conducted after every 2 cycles. The primary objective was to assess the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of NEO-201. The secondary objective was to assess the antitumor activity by RECIST v1.1. The exploratory objectives assessed pharmacokinetics and the effect of NEO-201 administration on immunologic parameters and their impact on clinical response. Results Seventeen patients (11 colorectal, 4 pancreatic and 2 breast cancers) were enrolled; 2 patients withdrew after the first dose and were not evaluable for DLT. Twelve of the 15 patients evaluable for safety discontinued due to disease progression and 3 patients discontinued due to DLT (grade 4 febrile neutropenia [1 patient] and prolonged neutropenia [1 patient] at DL 2, and grade 3 prolonged (> 72 h) febrile neutropenia [1 patient] at DL 1.5). A total of 69 doses of NEO-201 were administered (range 1–15, median 4). Common (> 10%) grade 3/4 toxicities occurred as follows: neutropenia (26/69 doses, 17/17 patients), white blood cell decrease (16/69 doses, 12/17 patients), lymphocyte decrease (8/69 doses, 6/17 patients). Thirteen patients were evaluable for disease response; the best response was stable disease (SD) in 4 patients with colorectal cancer. Analysis of soluble factors in serum revealed that a high level of soluble ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1186/s13046-023-02649-6 |
| DOI: |
10.1186/s13046-023-02649-6.pdf |
| DOI: |
10.1186/s13046-023-02649-6/fulltext.html |
| الإتاحة: |
https://doi.org/10.1186/s13046-023-02649-6Test |
| حقوق: |
https://creativecommons.org/licenses/by/4.0Test ; https://creativecommons.org/licenses/by/4.0Test |
| رقم الانضمام: |
edsbas.B0622A01 |
| قاعدة البيانات: |
BASE |
