Therapy of Small-cell Lung Cancer (SCLC) With a Topoisomerase-I-inhibiting Antibody-Drug Conjugate (ADC) Targeting Trop-2, Sacituzumab Govitecan

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small-cell lung cancer (mSCLC) patients. <p>Experimental Design: Sacituzumab govitecan was studied in patients with pretreated (median, 2; range, 1-7) mSCLC who received either 8 or 10 mg/kg i.v. on days 1 and 8 of 21-day cycles. The primary endpoints were safety and objective response rate (ORR); duration of response, progression-free survival (PFS), and overall survival (OS) were secondary endpoints.</p> <p>Results: Sixty percent of patients showed tumor shrinkage from baseline CTs. On an intention-to-treat basis (N= 50), the ORR was 14% (17% for 10 mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR>4 months), 34%; median PFS, 3.7 months; median OS, 7.5 months. There was a suggested improvement in PR, CBR, and PFS with sacituzumab govitecan in second-line patients who were sensitive to frontline therapy, but no difference between frontline chemosensitive vs chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan vs no topotecan therapy in a small subgroup. Grade >3 adverse events included neutropenia (34%), fatigue (13%), diarrhea (9%), and anemia (6%). Trop-2 tumor staining was not required for patient selection. No antibodies to the drug conjugate or its components were detected on serial blood collections.</p> <p>Conclusions: Sacituzumab govitecan appears to have a safe and effective therapeutic profile in heavily-pretreated, mSCLC patients, including those who are chemosensitive or chemoresistant to frontline chemotherapy. Additional studies as a monotherapy or combination therapy are warranted.

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