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

Abstract

Purpose: We evaluated a Trop-2-targeting antibody conjugated with SN-38 in metastatic small cell lung cancer (mSCLC) patients.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.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 the 10-mg/kg group); the median response duration, 5.7 months; the clinical benefit rate (CBR ≥4 months), 34%; median PFS, 3.7 months; and 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 first-line therapy, but no difference between first-line chemosensitive versus chemoresistant patients in the overall population. There was a statistically significant higher OS in those patients who received prior topotecan versus 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.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 first-line chemotherapy. Additional studies as a monotherapy or combination therapy are warranted. Clin Cancer Res; 23(19); 5711-9. ©2017 AACR.

• Authors: Jhanelle E Gray, Rebecca S Heist, Alexander N Starodub, D Ross Camidge, Ebenezer A Kio, Gregory A Masters, W Thomas Purcell, Michael J Guarino, Jamal Misleh, Charles J Schneider, Bryan J Schneider, Allyson Ocean, Tirrell Johnson, Leena Gandhi, Kevin Kalinsky, Ronald Scheff, Wells A Messersmith, Serengulam V Govindan, Pius P Maliakal, Boyd Mudenda, William A Wegener, Robert M Sharkey, David M Goldenberg
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 23 Issue 19 Pg. 5711-5719 (Oct 01 2017) ISSN: 1557-3265 [Electronic] United States
• PMID: 28679770 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article)
• Copyright: ©2017 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antigens, Neoplasm
• Cell Adhesion Molecules
• Immunoconjugates
• TACSTD2 protein, human
• Topoisomerase I Inhibitors
• DNA Topoisomerases, Type I
• sacituzumab govitecan
• Camptothecin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antigens, Neoplasm (immunology)
• Camptothecin (administration & dosage, adverse effects, analogs & derivatives, immunology)
• Cell Adhesion Molecules (antagonists & inhibitors, immunology)
• DNA Topoisomerases, Type I (genetics, immunology)
• Disease-Free Survival
• Drug-Related Side Effects and Adverse Reactions (classification, pathology)
• Female
• Humans
• Immunoconjugates (administration & dosage, adverse effects, chemistry)
• Kaplan-Meier Estimate
• Male
• Middle Aged
• Molecular Targeted Therapy
• Small Cell Lung Carcinoma (drug therapy, immunology, pathology)
• Topoisomerase I Inhibitors (administration & dosage, adverse effects)