Pipeline

Sacituzumab Govitecan (IMMU-132)

Background

The targeted delivery of drug by an antibody is an exciting approach in cancer treatment that has gained significant interest over the past few years. We believe our ADC programs differ from those of other companies, because we do not use supertoxic drugs, such as calicheamicin. Instead, we specifically look for moderately-toxic drugs, such as SN-38, which we attach at a much higher drug-to-antibody ratio than the ADCs using supertoxic drugs. We believe the use of a less-toxic drug, conjugated to the appropriate tumor-targeting antibody, will permit greater delivery of the drug over repeated cycles of therapy, thereby improving the therapeutic index, which is the ratio of efficacy to toxicity.

Sacituzumab govitecan is an ADC that contains SN-38, the active metabolite of irinotecan, approved by many Health Authorities including the U.S. Food and Drug Administration (FDA) as a chemotherapeutic for patients with cancer. SN-38 cannot be given directly to patients because of its toxicity and poor solubility. Sacituzumab govitecan was created at Immunomedics by conjugating SN-38 site-specifically and at a high ratio of drug to hRS7, our anti-TROP-2 antibody.

TROP-2 is a cell-surface receptor while over-expressed by many human tumors, including cancers of the breast, colon and lung, has limited expression in normal human tissues. hRS7 internalizes into cancer cells following binding to TROP-2, making it a suitable candidate for the delivery of cytotoxic drugs.

Sacituzumab govitecan has received Breakthrough Therapy designation from the FDA for the treatment of patients with triple-negative breast cancer (TNBC) who have failed prior therapies for metastatic disease. The regulatory agency has also granted this ADC Fast Track designation for patients with TNBC, and for patients with small-cell lung cancer (SCLC) or non-small-cell lung cancer (NSCLC). Fast Track designation is designed to expedite the development and review of applications for products intended for the treatment of a serious or life-threatening disease or condition. This ADC has also been designated an orphan drug by the FDA for the treatment of patients with SCLC or pancreatic cancer in the U.S. and by the European Medicines Agency (EMA) for the treatment of patients with pancreatic cancer in the European Union.

Clinical Studies

Solid Cancers

Sacituzumab govitecan is currently being evaluated in a multicenter Phase 2 study in patients with solid cancers. Please refer to the Company Presentation for updated results from this multicenter study.

References
  • Govindan SV, Goldenberg DM. Designing immunoconjugates for cancer therapy. Expert Opin Biol Ther. 2012 Jul;12(7):873-90. doi: 10.1517/14712598.2012.685153. Review.

  • Picozzi VJ, Ocean AJ, Starodub AN, Thomas SS, Maliakal PP, Govindan SV, Hamburger SA, Sharkey RM, Goldenberg DM. IMMU-132, a new antibody-drug conjugate (ADC), evaluated in patients with advanced, metastatic, pancreatic ductal adenocarcinoma (mPC): Results of a Phase I/II trial. Poster presented at American Association for Cancer Research (AACR) Special Conference on Pancreatic Cancer:Innovations in Research and Treatment, Abstr. #B99, May 18-21, 2014.

  • Goldenberg DM, Cardillo TM, Sharkey RM, McBride WJ, Rossi EA, Chang Chien-Hsing, Govindan SV. SN-38 antibody-drug conjugates as a novel platform for solid cancer therapy: preclinical science. American Association for Cancer Research (AACR) 2014 Annual Meeting, Abstr. #2904, April 7, 2014.

  • Starodub AN, Ocean AJ, Shah MA, Vahdat LT, Chuang E, Guarino MJ, Picozzi VJ, Thomas SS, Maliakal PP, Govindan SV, Wegener WA, Sharkey RM, Goldenberg DM. SN-38 antibody-drug conjugate (ADC) targeting Trop-2, IMMU-132, as a novel platform for the therapy of diverse metastatic solid cancers: Initial clinical results. American Association for Cancer Research (AACR) 2014 Annual Meeting, Abstr. #CT206, April 7, 2014.

  • Starodub AN, Ocean AJ, Guarin MJ, Chuang E, Shah MA, Tagawa S, Picozzi VJ, Thomas SS, Maliakal PP, Wegener WA, Sharkey RM, Govindan SV, Goldenberg DM. Safety, efficacy, and pharmacokinetics of a new humanized anti-Trop-2 antibody-SN-38 conjugate (IMMU-132) for the treatment of diverse epithelial cancers: Phase I clinical experience. AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics Meeting. (Abstr. #C67), October 22, 2013.

  • Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Goldenberg DM. Humanized anti-Trop-2 IgG-SN-38 conjugate for effective treatment of diverse epithelial cancers: preclinical studies in human cancer xenograft models and monkeys. Clin Cancer Res. 2011 May 15;17(10):3157-69. doi: 10.1158/1078-0432.CCR-10-2939. Epub 2011 Mar 3. PMID: 21372224.

  • Cardillo TM, Sharkey RM, Rossi DL, Arrojo R, Mostafa A, Goldenberg DM. Synthetic lethality exploitation by an anti-Trop-2-SN-38 antibody-drug conjugate, IMMU-132, plus PARP-inhibitors in BRCA1/2-wild-type triple-negative breast cancer. Clin Cancer Res. 2017 Jan 9. pii: clincanres.2401.2016. doi: 10.1158/1078-0432.CCR-16-2401. [Epub ahead of print]

  • Govindan SV, Sharkey RM, Goldenberg DM. Prospects and progress of antibody-drug conjugates in solid tumor therapies. Expert Opin Biol Ther. 2016 Jul;16(7):883-93. doi:10.1517/14712598.2016.1173203. Review

  • Faltas B, Goldenberg DM, Ocean AJ, Govindan SV, Wilhelm F, Sharkey RM, Hajdenberg J, Hodes G, Nanus DM, Tagawa ST. Sacituzumab Govitecan, a Novel Antibody--Drug Conjugate, in Patients With Metastatic Platinum-Resistant Urothelial Carcinoma. Clin Genitourin Cancer. 2016 Feb;14(1):e75-9. doi: 10.1016/j.clgc.2015.10.002.

  • Sharkey RM, McBride WJ, Cardillo TM, Govindan SV, Wang Y, Rossi EA, Chang CH, Goldenberg DM. Enhanced Delivery of SN-38 to Human Tumor Xenografts with an Anti-Trop-2-SN-38 Antibody Conjugate (Sacituzumab Govitecan). Clin Cancer Res. 2015 Nov 15;21(22):5131-8. doi: 10.1158/1078-0432.CCR-15-0670.

  • Goldenberg DM, Cardillo TM, Govindan SV, Rossi EA, Sharkey RM. Trop-2 is a novel target for solid cancer therapy with sacituzumab govitecan (IMMU-132), an antibody-drug conjugate (ADC). Oncotarget. 2015 Sep 8;6(26):22496-512.

  • Starodub AN, Ocean AJ, Shah MA, Guarino MJ, Picozzi VJ Jr, Vahdat LT, Thomas SS, Govindan SV, Maliakal PP, Wegener WA, Hamburger SA, Sharkey RM, Goldenberg DM. First-in-Human Trial of a Novel Anti-Trop-2 Antibody-SN-38 Conjugate, Sacituzumab Govitecan, for the Treatment of Diverse Metastatic Solid Tumors. Clin Cancer Res. 2015 Sep 1;21(17):3870-8. doi: 10.1158/1078-0432.CCR-14-3321.

  • Cardillo TM, Govindan SV, Sharkey RM, Trisal P, Arrojo R, Liu D, Rossi EA, Chang CH, Goldenberg DM. Sacituzumab Govitecan (IMMU-132), an Anti-Trop-2/SN-38 Antibody-Drug Conjugate: Characterization and Efficacy in Pancreatic, Gastric, and Other Cancers. Bioconjug Chem. 2015 May 20;26(5):919-31. doi: 10.1021/acs.bioconjchem.5b00223.




Immunomedics - Physicians