The U.S. Food and Drug Administration (FDA) designating as a Fast Track development program the investigation of sacituzumab govitecan (IMMU-132), Immunomedics, Inc. lead antibody-drug conjugate (ADC), for the treatment of patients with triple-negative breast cancer or TNBC who have failed prior therapies for metastatic disease.

The Fast Track programs, established under the FDA Modernization Act of 1997, are designed to facilitate drug development and to expedite the review of new drugs that are intended to treat serious or life threatening conditions. Compounds selected must demonstrate the potential to address unmet medical needs. The Fast Track designation allows for close and frequent interaction with the agency. A designated Fast Track drug may also be considered for priority review with a shortened review time, rolling submission, and accelerated approval if applicable. The designation does not, however, guarantee approval or expedited approval of any application for the product.

Sacituzumab govitecan
Sacituzumab govitecan is a novel antibody-drug conjugate or ADC developed by Immunomedics, a clinical-stage biopharmaceutical company. The drug conjugates the moderately-toxic drug, SN-38, site-specifically and at a high ratio of drug to antibody hRS7, a humanized antibody that binds to the trophoblast cell-surface antigen (TROP-2), also known as the epithelial glycoprotein-1 antigen or EGP-1.

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TROP-2 is expressed by many human tumors, such as cancers of the breast, cervix, colon and rectum, kidney, liver, lung, ovary, pancreas, and prostate, but with only limited expression in normal human tissues. The antibody, hRS7, internalizes into cancer cells following binding to TROP-2, making it a suitable candidate for the delivery of cytotoxic drugs.

The moderately-toxic drug SN-38 is the active metabolite of irinotecan, also know as Camptosar, an anti-cancer or antineoplastic chemotherapy drug classified as a plant alkaloid and topoisomerase I inhibitor. The drug, a part of combination therapies, is used to treat certain solid cancers. It is the a standard therapy for patients with metastatic colorectal cancer, but has major gastrointestinal and hematological toxicities. The pharmacology and properties of the drug are well-known.

By attaching SN-38 to tumor-targeting antibodies, delivery of SN-38 to the tumor may be increased several-fold while mitigating systemic toxicity. Preclinical studies have indicated that sacituzumab govitecan delivers up to 135-times the amount of SN-38 to a human pancreatic tumor xenograft than when irinotecan is given. In various animal models of human cancers, the antibody-drug conjugate significantly improved survival and tumor regression.

Trial results
Based on the Immunomedics’ current results with patients having advanced triple-negative breast cancer, which is a serious and life-threatening disease for which there are few therapy options, as well as the company’s clinical development plans for this ADC, Immunomedics gained this designation.

Most difficult type of breast cancer to treat
Triple-negative breast cancer represents breast cancers that are negative for estrogen and progesterone receptors, as well as human epidermal growth factor receptor 2, or HER2. This type of breast cancer comprises about 15-20% of all invasive breast cancers and is more prevalent in young and African-American women.

Despite the fact that initial responses with chemotherapy are high, triple-negative breast cancer characteristically has a high recurrence rate and is perhaps the most difficult type of breast cancer to treat successfully with current cytotoxic agents. According to a published report, the median survival for patients with metastatic triple-negative breast cancer is estimated to be 13 months.[1] There are currently no targeted treatments available for triple-negative breast cancer.

Patients with triple-negative breast cancer enrolled to-date have had a median of 4 prior therapies (range, 1-15), including combinations of conventional and experimental drugs. To-date, approximately 30% of assessable patients has shown an objective response rate (complete and partial remissions) by computed tomography, where shrinkage of tumors ranging from 30% to 100% has been observed. The major toxicity is neutropenia, which has been manageable by dose reductions or giving myeloid growth factors. Unlike the parent drug of SN-38, irinotecan, sacituzumab govitecan has not caused severe diarrhea.

Other solid tumors
Immunomedics is also evaluating this ADC in other solid tumors showing objective responses, such as in patients with small-cell and non-small cell lung, colorectal, esophageal, and urinary bladder cancers.

Previously, FDA also granted Fast Track status to sacituzumab govitecan for the therapy of patients with small-cell lung cancer, which also constitutes an unmet medical need and where sacituzumab govitecan has induced objective responses. Sacituzumab govitecan has also been designated an orphan drug by FDA for the treatment of patients with small-cell lung or pancreatic cancers.

Commenting on tis news, Immunomedics’ president and Chief Executive Officer, Cynthia L. Sullivan, said: “We are pleased to receive this Fast Track designation from FDA. We plan to discuss with FDA and our medical advisers the registration pathway for this valuable agent in breast cancer, and talks with potential licensing partners are continuing,” she reiterated. “We are close to completing enrollment of about 50 patients with metastatic triple negative breast cancer, while we continue to study other indications as well,” Sullivan advised.