FDA Grants Breakthrough Therapy Designation for Sacituzumab Govitecan for the Treatment of TNBC

Antibody-drug conjugate for treatment of patients with triple-negative breast cancer who have failed at least 2 prior therapies for metastatic disease

On 5 February 2016, Immunomedics, Inc. announced that its lead investigational antibody-drug conjugate, sacituzumab govitecan, or IMMU-132, has received Breakthrough Therapy Designation from the US Food and Drug Administration (FDA) for the treatment of patients with triple-negative breast cancer (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).

The company stated that they continue to assess partnering opportunities while completing the scale-up manufacturing and regulatory activities for an international, randomised, controlled, registration trial in TNBC, based on the Special Protocol Assessment agreement that was already granted by the FDA.

IMMU-132 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 (ADC) has increased expression in a large number of solid cancers. To date, about 300 patients with diverse cancer types have been enrolled.

Breakthrough Therapy Designation was created as part of the 2012 FDA Safety and Innovation Act 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.

Sacituzumab govitecan, or IMMU-132, is a first-in-class ADC developed by the company 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, 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 US, and for the treatment of patients with pancreatic cancer in the European Union.

The company stated that a press release, in addition to historical information, may contain forward-looking statements.

Immunomedics is a clinical-stage biopharmaceutical company developing monoclonal antibody-based products for the targeted treatment of cancer, autoimmune disorders and other serious diseases. Immunomedics’ most advanced candidate is 90Y-clivatuzumab tetraxetan. This radiolabeled antibody is in an international phase III registration trial in patients with advanced pancreatic cancer. It is expected that patient enrollment should be completed in calendar year 2016. Immunomedics’ portfolio of investigational products also includes ADCs and their most advanced ADCs are sacituzumab govitecan (IMMU-132) and labetuzumab govitecan (IMMU-130), which are in phase II trials for a number of solid tumours and metastatic colorectal cancer. Immunomedics has a research collaboration with Bayer to study epratuzumab as a thorium-227-labeled antibody. Immunomedics has other ongoing collaborations in oncology with independent cancer study groups. The IntreALL Inter-European study group is conducting a large, randomised phase III trial combining epratuzumab with chemotherapy in children with relapsed acute lymphoblastic leukemia at clinical sites in Australia, Europe, and Israel. Immunomedics also has a number of other product candidates that target solid tumours and hematologic malignancies, as well as other diseases, in various stages of clinical and preclinical development.