Labetuzumab Govitecan (IMMU-130)
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.
Our second investigational solid-tumor ADC involves our anti-CEACAM5 antibody, labetuzumab, conjugated to SN-38. The agent is currently being studied in patients with metastatic colorectal cancer (mCRC) who have received at least one prior irinotecan-containing regimen and had an elevated blood titer of carcinoembryonic antigen (CEA). Several dosing schedules were evaluated in three Phase I studies. Labetuzumab govitecan showed therapeutic activity in all three trials, but a more frequent dosing schedule, with administrations of the ADC once or twice-weekly for two weeks followed by a week off, appeared to be more active in patients with mCRC than when administered every other week.
In the current Phase 2 study, patients with metastatic colorectal cancer are being treated in three-week cycles, receiving IMMU-130 either once weekly or twice-weekly for the first two weeks followed by one week of rest. Please refer to the Company Presentation for updated results from this multicenter study.
- 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.
- Segal NH, Dotan E, Berlin JD, Storadub AN, Guarino MJ, Saltz LB, Maliakal PP, Govindan SV, Wegener WA, Sharkey RM, Goldenberg DM. IMMU-130, an SN-38 antibody-drug conjugate (ADC) targeting CEACAM5, is therapeutically active in metastatic colorectal cancer (mCRC): Initial clinical results of two Phase I studies. . American Association for Cancer Research (AACR) 2014 Annual Meeting, Abstr. #CT211, April 7, 2014.
- Segal NH, Verghis J, Govindan S, Maliakal P, Sharkey RM, Wegener WA, Goldenberg DM, Saltz LB. Initial results of a new antibody-drug conjugate (ADC), IMMU-130 (labetzumab-SN38), in patients with metastatic colorectal cancer (mCRC). European Cancer Congress (Abstr. # 2359), September 29, 2013.
- Segal NH, Verghis J, Govindan S, Maliakal P, Sharkey RM, Wegener WA, Goldenberg DM, Saltz LB. A Phase I study of IMMU-130 (labetuzumab-SN38) anti-CEACAM5 antibody-drug conjugate (ADC) in patients with metastatic colorectal cancer (mCRC). Proc. Amer. Assoc. Cancer Res. 104th Annual Meeting, 54 (Suppl Late-Breaking): 54-55 (Abstr. #LB-159), 2013.
- Govindan SV, Cardillo TM, Moon SJ, Hansen HJ, Goldenberg DM. CEACAM5-targeted therapy of human colonic and pancreatic cancer xenografts with potent labetuzumab-SN-38 immunoconjugates. Clin Cancer Res. 2009 Oct 1;15(19):6052-61. doi: 10.1158/1078-0432.CCR-09-0586. Epub 2009 Sep 29.