Abstract CT155: Phase 2 study of sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate (ADC), in patients with pretreated metastatic small-cell lung cancer (mSCLC)
Authors: Gray Jhanelle E. , Heist Rebecca S. , Starodub Alexander N. , Camidge D. Ross , Kio Ebenezer , Masters Gregory , Purcell W. Thomas , Guarino Michael J. , Misleh Jamal , Schneider Charles J. , Schneider Bryan J. , Ocean Allyson J. , Johnson Tirrell , Gandhi Leena , Kalinsky Kevin , Govindan Serengulam V. , Maliakal Pius , Mudenda Boyd , Wegener William A. , Sharkey Robert M. , Goldenberg David M. 
Published: July 2017

Abstract
Introduction: Sacituzumab govitecan (IMMU-132) is an antibody-drug conjugate (ADC) delivering SN-38, a topoisomerase-1 inhibitor, to mSCLC cells expressing Trop-2. We are studying the safety/tolerability and efficacy of IMMU-132 in patients with relapsed/refractory mSCLC who had received a platinum-containing first-line regimen.
Experimental Procedure: Patients received 8 or 10 mg/kg IV IMMU-132 on days 1 and 8 of repeated 21-day cycles. Objective tumor response (ORR) was determined by RECISTv1.1 in patients receiving at least one treatment cycle, and progression-free survival (PFS) and overall survival (OS) in all patients by Kaplan-Meier methods. (ClinicalTrials.gov, NCT01631552)
Summary of New Unpublished Data: A total of 53 patients (23/30 M/F, median 63 years old) with 1-7 (median 2) prior lines of therapy were enrolled between November, 2013 and June, 2016. Immunohistochemistry of evaluable archival tumor specimens for Trop-2 expression (N=26) showed 92% positivity (61% moderately to strongly positive). They received up to 32 treatment cycles (median 5); the most frequent Grade &gt;3 adverse events were neutropenia (34%), fatigue (13%) and diarrhea (9%). Four patients did not complete one cycle of treatment. In the other 49 patients (14 at 8 mg/kg, 35 at 10 mg/kg), there were 7 confirmed PRs and 21 SDs as best response. The resulting ORR rate was 14% (7/49), with a median duration and time-to-progression of a response of 4.0 and 7.6 mos, respectively, and the clinical benefit rate (PR+SD &gt;4 mos) was 35% (17/49). The ORR rate was similar in pts who were sensitive (&gt;3 mos response) or resistant (&lt;3 mos) to 1st-line therapy [13% (3/23) vs 15% (4/26), respectively]. In 2nd-line setting, IMMU-132 had a confirmed ORR rate of 14% (3/21), and a clinical benefit rate of 38% (8/21). This compares well to recent results with topotecan having an ORR of 13-16% in 2nd-line. Comparing dose levels, ORR was 17% (6/35) with 10 mg/kg vs 7% (1/14) with 8 mg/kg, with little difference in toxicity. Median PFS and OS in all 53 patients was 3.7 mos (95% CI, 2.0 - 4.3) and 7.0 mos (95% CI, 5.5 - 8.3), respectively, and included 6 long-term survivors (12.7 - 25.4 months). No antibody response to the ADC or antibody was detected despite multiple therapy cycles.
Conclusion: These interim results demonstrate encouraging activity in patients with late-stage mSCLC having a high expression of Trop-2. Even after failing 1st-line platinum chemotherapy or 2nd-line topotecan therapy, IMMU-132 showed promising activity, and has a manageable toxicity profile. IMMU-132 given at 10 mg/kg on day 1 and 8 of a 3-week cycle was selected for further clinical evaluation in this population.
Citation Format: Jhanelle E. Gray, Rebecca S. Heist, Alexander N. Starodub, D. Ross Camidge, Ebenezer Kio, Gregory Masters, W. Thomas Purcell, Michael J. Guarino, Jamal Misleh, Charles J. Schneider, Bryan J. Schneider, Allyson J. Ocean, Tirrell Johnson, Leena Gandhi, Kevin Kalinsky, Serengulam V. Govindan, Pius Maliakal, Boyd Mudenda, William A. Wegener, Robert M. Sharkey, David M. Goldenberg. Phase 2 study of sacituzumab govitecan (IMMU-132), an anti-Trop-2/SN-38 antibody-drug conjugate (ADC), in patients with pretreated metastatic small-cell lung cancer (mSCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr CT155. doi:10.1158/1538-7445.AM2017-CT155