The investigational antibody-drug conjugate, sacituzumab govitecan, also know as IMMU-132 (Immunomedics), has received Breakthrough Therapy Designation from the U.S. Food and Drug Administration (FDA) for the treatment of patients with triple-negative breast cancer or TNBC who have failed at least 2 prior therapies for metastatic disease.

The Breakthrough Therapy Designation was supported by a Phase II study in patients with metastatic TNBC who had received a median of 5 prior therapies (range, 2 – 12).

Triple-negative breast cancer is a serious disease, with an annual incidence estimated to be about 40,000 people, 20,000 for metastatic TNBC, in the United States. As the name implies, TNBC does not express estrogen, progesterone or the HER2 receptor, and is, therefore, insensitive to most of the available targeted therapies for breast cancer treatment, including HER2-directed therapy such as trastuzumab (Herceptin®; Genentech/Roche), and endocrine therapies such as tamoxifen (Nolvadex®; AstraZeneca) or the aromatase inhibitors. The median overall survival is 6-13 months and the median PFS is usually 3-4 months. There is currently no single standard chemotherapy to treat patients with relapsed/refractory metastatic TNBC. Rapid relapse, with visceral and brain metastases, is very common.

Novel treatment option
Sacituzumab govitecan is a first-in-class antibody-drug conjugate designed to deliver a specific payload of a chemotherapeutic directly to the tumor while reducing overall toxic effects that are usually found with conventional administration of these chemotherapeutic agents.

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The drug candidate is developed by conjugating the moderately-toxic drug, SN-38, site-specifically and at a high ratio of drug to antibody, to a humanized antibody that targets the Trop-2 receptor expressed by many solid cancers.

SN-38 is the active metabolite of irinotecan (Camptosar), which is used to treat certain solid cancers as a part of combination therapies, so its pharmacology and properties are well- known. The ADC has received Fast Track designation from the FDA for the treatment of patients with triple-negative breast cancer, small-cell and non-small-cell lung cancers, and has also been designated an orphan drug for the treatment of patients with small-cell lung or pancreatic cancer in the U.S., and for the treatment of patients with pancreatic cancer in the European Union.

Validating potential
“We believe Breakthrough Therapy Designation for sacituzumab govitecan further validates this potential therapeutic for patients with TNBC, and we are delighted to receive this important recognition,” noted Cynthia L. Sullivan, President and Chief Executive Officer. “We continue to assess partnering opportunities while completing the scale-up manufacturing and regulatory activities for an international, randomized, controlled, registration trial in TNBC, based on the Special Protocol Assessment agreement that was already granted by the FDA,” she added.

“[Sacituzumab govitecan]  is also in Phase II trials in patients with advanced, heavily-pretreated, non-small-cell lung cancer, small-cell lung cancer, and urothelial cancers, where encouraging results have been observed. The Trop-2 receptor targeted by this antibody- drug conjugate has increased expression in a large number of solid cancers. To date, we have enrolled about 300 patients with diverse cancer types,” Sullivan further stated.

Breakthrough Therapy Designation
Breakthrough Therapy Designation was created as part of the 2012 FDA Safety and Innovation Act (FDASIA) to expedite the development and review of a drug that is intended, alone or in combination with one or more other drugs, to treat a serious or life-threatening disease or condition, and preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development.

Expanding portfolio 
In addition to sacituzumab govitecan Immunomedics’ portfolio of investigational products also includes labetuzumab govitecan or  IMMU-130, which is in Phase II trials for a number of solid tumors and metastatic colorectal cancer.

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