Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas.

Salvatore Lopez, Emanuele Perrone, Stefania Bellone, Elena Bonazzoli, Burak Zeybek, Chanhee Han, Joan Tymon-Rosario, Gary Altwerger, Gulden Menderes, Anna Bianchi, Luca Zammataro, Aranzazu Manzano, Paola Manara, Elena Ratner, Dan-Arin Silasi, Gloria S. Huang, Masoud Azodi, Peter E. Schwartz, Francesco Raspagliesi, Roberto AngioliNatalia Buza, Pei Hui, Heather M. Bond, Alessandro D. Santin

Research output: Contribution to journalArticlepeer-review

Abstract

BACKGROUND: Uterine and ovarian carcinosarcomas (CS) are rare cancers with poor prognosis. Sacituzumab-govitecan (SG) is a new class of antibody-drug-conjugate (ADC) targeting the human-trophoblast-cell-surface marker (Trop-2) conjugated with the active metabolite of irinotecan (SN-38). We evaluated the efficacy of SG against biologically aggressive CS. METHODS: Trop-2 expression was evaluated in 10 formalin-fixed-paraffined-embedded (FFPE) CS by immunohistochemistry and 9 primary CS cell-lines by flow-cytometry. One Trop-2 low/negative (SARARK14) and two Trop-2 positive (SARARK4, SARARK9) cell-lines were tested in cell-viability assays . The in vivo antitumor activity of SG was tested in xenografts models (ie, SARARK9) with strong Trop-2 expression. RESULTS: Strong/diffuse staining was seen in 303/10) of FFPE tumors and 333/9) of primary CS cell lines. Trop-2 positive cell-lines (SARARK4, SARARK9) showed higher sensitivity to SG in vitro when compared to Trop-2 low/negative (SARARK14) cell lines. In xenografts, twice-weekly intravenous administration of SG for three weeks showed a significant tumor growth inhibition when compared to control, to ADC control and to the naked AB (p=0.004, p=0.007 and p=0.0007, respectively). SG significantly improved overall survival at 90 days when compared to control groups (ptextless0.0001). CONCLUSION: SG may represent a novel class of active drugs for carcinosarcomas patients overexpressing Trop-2.
Original languageEnglish
Pages (from-to)560-570
Number of pages11
JournalOncotarget
Volume11
Issue number5
DOIs
Publication statusPublished - Feb 1 2020

Keywords

  • IMMU-132
  • sacituzumab govitecan
  • trop-2
  • uterine carcinosarcoma

Fingerprint Dive into the research topics of 'Preclinical activity of sacituzumab govitecan (IMMU-132) in uterine and ovarian carcinosarcomas.'. Together they form a unique fingerprint.

Cite this