Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial
| Autor: | Jordan Berlin, Takefumi Komiya, Gregory A. Masters, J.M. Lang, Linda T. Vahdat, RL Moroose, E.A. Kio, Kevin Kalinsky, Robert M. Sharkey, Jenny C. Chang, T. Goswami, Vincent J. Picozzi, William A. Wegener, Joyce O'Shaughnessy, Alessandro D. Santin, Alexander Starodub, Q. Hong, Wells A. Messersmith, Allyson J. Ocean, David M. Goldenberg, Jhanelle E. Gray, Pius Maliakal, Aditya Bardia |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Immunoconjugates Lung Neoplasms Population Neutropenia Antibodies Monoclonal Humanized Gastroenterology 03 medical and health sciences 0302 clinical medicine Internal medicine Multicenter trial medicine Humans education education.field_of_study business.industry Endometrial cancer Cancer Hematology Middle Aged medicine.disease 030104 developmental biology Oncology Tolerability 030220 oncology & carcinogenesis Sacituzumab govitecan Camptothecin Female business Febrile neutropenia |
| Zdroj: | Annals of oncology : official journal of the European Society for Medical Oncology. 32(6) |
| ISSN: | 1569-8041 |
| Popis: | Background Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. Patients and methods Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. Results In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). Conclusions SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors. |
| Databáze: | OpenAIRE |
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