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

作者：Aditya Bardia, Wells A. Messersmith, Ebenezer A. Kio, Jordan D. Berlin, Linda T. Vahdat, Gregory A. Masters, R.L. Moroose, Alessandro Davide Santin, Kevin M. Kalinsky, Vincent J. Picozzi, Joyce A O'Shaughnessy, Jhanelle E. Gray, Takefumi Komiya, Joshua Michael Lang, Jenny C. Chang, Alexander Starodub, David M. Goldenberg, Robert M. Sharkey, Pius P. Maliakal, Q. Hong, William A. Wegener, Trishna Goswami, Allyson J. Ocean · 发表于：Annals of Oncology · 年份：2021 · DOI：10.1016/j.annonc.2021.03.005 · 被引用次数：400 · 研究领域：HER2/EGFR in Cancer Research、Advanced Breast Cancer Therapies、Cancer Cells and Metastasis

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...