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

Clin Cancer Res. 2017 Oct 1;23(19):5711-5719. doi: 10.1158/1078-0432.CCR-17-0933. Epub 2017 Jul 5.


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.

Publication types

  • Clinical Trial, Phase I
  • Clinical Trial, Phase II

MeSH terms

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


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