Abstract Background: mTNBC has an aggressive course with limited therapeutic options. Sacituzumab govitecan (IMMU-132) is a novel antibody drug conjugate consisting of SN-38, the active metabolite of the topoisomerase I inhibitor, irinotecan, conjugated to a humanized mAb targeting Trop-2, which is highly expressed in most epithelial cancers, including TNBC. A phase I/II basket trial (NCT01631552) was conducted in patients (pts) with multiple, advanced epithelial cancers. We previously reported preliminary results in mTNBC (N=69; objective response rate [ORR] = 30%, Bardia et al., JCO 2017;35:2141-2148). In 2016, sacituzumab govitecan was granted Breakthrough Designation based on this encouraging data, and we resumed enrollment in a more defined patient population (≥3rd-line setting in mTNBC). Methods: Pts received sacituzumab govitecan on days 1 & 8 of a 21-day cycle until progression or unacceptable toxicity. Eligibility included > 2 prior lines of therapy for metastatic disease, measurable disease by CT or MRI and prior taxane. Efficacy was assessed locally by RECIST 1.1 and confirmed by independent centralized blinded review. ORR, DOR, progression-free survival (PFS) and overall survival (OS) were determined. Adverse events (CTCAE v4.0), immunogenicity, and Trop-2 expression in archived tumor samples, when available, were evaluated. Results: 110 mTNBC pts (109 female, 1 male; median age 55 yrs, range 31-81), including 53 from the previously reported cohort of 69 pts who had received ≥2 prior regimens for metastatic disease, were accrued between 7/2013 and 2/2017. As of data cutoff on 6/30/2017, 71 are deceased, 23 in long-term follow-up, and 16 still on treatment. All pts were treated at the 10 mg/kg IMMU-132 dose level, receiving 14.5 median doses (range 1-88). Treatment was well tolerated, with no treatment-related deaths, 2 treatment discontinuations for toxicity, and no anti-drug antibodies detected. Grade ≥ 3 toxicity (≥10%) included neutropenia, 39%; leukopenia, 14%; anemia, 10%; the incidence of febrile neutropenia was low (7%). By local radiologist assessment, the ORR is 34% (37/110), including 3 CRs and 34 PRs, the clinical benefit rate (CBR: CR+PR+SD>6 mo.) is 46%, the KM median DOR and PFS are 7.6 mo. (95% CI: 4.8 to 11.3) and 5.5 mo. (95% CI: 4.8 to 6.6), respectively, including 10% (11 pts) with long-term PFS (12 to 30+ mo.), and the KM median OS is 12.7 mo. (95% CI: 10.8 to 13.6). Results of the independent central blinded review along with sensitivity analyses of prior treatment regimens, including checkpoint inhibitor use, and exploratory biomarker analysis of Trop-2 expression will be presented at the meeting. Conclusions: Sacituzumab govitecan demonstrated significant clinical activity as a single agent in the ≥3rd-line setting for patients with relapsed/refractory mTNBC. Given the high unmet medical need, data from this trial is being submitted for consideration of accelerated approval, and a global confirmatory randomized Phase III trial (NCT02574455) is underway. Additional studies including rational combinations are currently being evaluated for mTNBC and other breast cancer subsets. Citation Format: Bardia A, Vahdat LT, Diamond J, Kalinsky K, O'Shaughnessy J, Moroose RL, Isakoff SJ, Tolaney SM, Santin AD, Abramson V, Shah NC, Govindan SV, Maliakal P, Sharkey RM, Wegener WA, Goldenberg DM, Mayer IA. Sacituzumab govitecan (IMMU-132), an anti-Trop-2-SN-38 antibody-drug conjugate, as ≥3rd-line therapeutic option for patients with relapsed/refractory metastatic triple-negative breast cancer (mTNBC): efficacy results [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr GS1-07.
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Feb 20, 2023
