Background: Patients with metastatic TNBC have an aggressive disease with limited therapy options. The duration of response with standard chemotherapy is usually short, with median PFS of about 3-4 months, and there is an unmet need for better therapies. Trop-2 is highly expressed in most epithelial cancers, including TNBC ( > 90%). IMMU-132 is a conjugate of a humanized anti-Trop-2 (trophoblast cell-surface antigen) mAb coupled site-specifically to SN-38 (7.6 moles SN-38/IgG), the active metabolite of irinotecan, using a proprietary linker. Methods: In an ongoing Phase I/II clinical trial (ClinicalTrials.gov, NCT01631552), patients with metastatic TNBC patients refractory or relapsing to prior therapies, including topoisomerase inhibitors, received IMMU-132 i.v. on days 1 and 8 of 21-day treatment cycles. Treatment was continued based on tolerance or until progression, with safety and response assessments (RECIST1.1) made every week and at 8-12 weeks, respectively. Dose reductions/delays allowed most patients to continue treatment until progression. Results: As of Feb 2, 2015, a total of 174 pts with relapsed/refractory diverse epithelial tumors have been treated with IMMU-132. Forty-eight pts with TNBC were treated: median age = 51 ys (range, 33-81), median of 4 prior chemotherapies (range, 1-11). In TNBC, Grade 3/4 toxicities included neutropenia (G3, 24%; G4, 6%) and febrile neutropenia (G4, 3%). Other G3 toxicities included diarrhea (3%), anemia (3%), leucopenia (3%), lymphopenia (3%), caecitis (3%). No pt developed antibodies to the conjugate; no one discontinued due to toxicity. Thirty-four TNBC pts had at least 1 response assessment, with an objective response rate (ORR) of 21% (including one complete response), a disease stabilization rate (CR+PR+SD) of 74%, and a clinical benefit ratio with CR+PR+SD ≥ 6 mo = 37% (7 of 15 pt with SD are still on treatment). Conclusions: IMMU-132 therapy is associated with encouraging clinical activity and limited toxicity in patients with metastatic TNBC s/p multiple prior lines of therapy. It warrants further evaluation for this refractory disease. Clinical trial information: NCT01631552