• Alexander N Starodub, Allyson J Ocean, Manish A Shah, Michael J Guarino, Vincent J Picozzi, Linda T Vahdat, Sajeve S Thomas, Serengulam V Govindan, Pius P Maliakal, William A Wegener, Steven A Hamburger, Robert M Sharkey, and David M Goldenberg.
• Indiana University Health Goshen Center for Cancer Care, Goshen, Indiana.
• Clin Cancer Res. 2015 Sep 1; 21 (17): 3870-8.

PurposeSacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) targeting Trop-2, a surface glycoprotein expressed on many epithelial tumors, for delivery of SN-38, the active metabolite of irinotecan. This phase I trial evaluated this ADC as a potential therapeutic for pretreated patients with a variety of metastatic solid cancers.Experimental DesignSacituzumab govitecan was administered on days 1 and 8 of 21-day cycles, with cycles repeated until dose-limiting toxicity or progression. Dose escalation followed a standard 3 + 3 scheme with 4 planned dose levels and dose delay or reduction allowed.ResultsTwenty-five patients (52-60 years old, 3 median prior chemotherapy regimens) were treated at dose levels of 8 (n = 7), 10 (n = 6), 12 (n = 9), and 18 (n = 3) mg/kg. Neutropenia was dose limiting, with 12 mg/kg the maximum tolerated dose for cycle 1, but too toxic with repeated cycles. Lower doses were acceptable for extended treatment with no treatment-related grade 4 toxicities and grade 3 toxicities limited to fatigue (n = 3), neutropenia (n = 2), diarrhea (n = 1), and leukopenia (n = 1). Using CT-based RECIST 1.1, two patients achieved partial responses (triple-negative breast cancer, colon cancer) and 16 others had stable disease as best response. Twelve patients maintained disease control with continued treatment for 16 to 36 weeks; 6 survived 15 to 20+ months. No preselection of patients based on tumor Trop-2 expression was done.ConclusionsSacituzumab govitecan had acceptable toxicity and encouraging therapeutic activity in patients with difficult-to-treat cancers. The 8 and 10 mg/kg doses were selected for phase II studies.©2015 American Association for Cancer Research.

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