(NIEHS, nih.gov)
21 Feb. 2019. A clinical trial shows a treatment combining an antibody and chemotherapy drug invokes a response and longer survival time in many patients with metastatic triple-negative breast cancer. Results from the study appear in today’s issue of the New England Journal of Medicine (registration required).
The trial is testing the drug sacituzumab govitecan being developed by biotechnology company Immunomedics Inc. in Morris Plains, New Jersey. Sacituzumab govitecan is in a class of drugs called antibody-drug conjugates, which join highly-specific synthetic antibodies with other compounds or additives to combine the targeting of antibodies with cancer-killing power of the drugs being delivered, thus avoiding in many people the serious adverse effects of conventional chemotherapy.
In this case, sacituzumab govitecan targets trophoblast cell-surface antigen 2 or Trop-2 proteins that overproduce on the surface of tumor cells in a number of solid-tumor cancers and help drive tumor growth. In sacituzumab govitecan, an antibody called hRS7 targets Trop-2 proteins that combines with SN-38, a metabolite of the drug irinotecan and approved by FDA as a chemotherapy.
The clinical trial testing sacituzumab govitecan enrolled some 500 patients at 12 sites in the U.S. with a range of advanced-stage solid tumor cancers. Participants in the early- and mid-stage trial were already treated with chemo and radiation therapy, and received sacituzumab govitecan once a week for 2 weeks, with a the third week off. This cycle is repeated until the patients show either toxicity from the treatments or the cancer progresses indicating a failure to respond. The study has no placebo or control group.
The journal article reports on results from 108 patients with metastatic triple-negative breast cancer, where the tumors do not express hormonal or HER2 receptor proteins that are targets for most cancer drugs. Among this group, patients previously received as many as 10 conventional treatments, with half of the patients receiving 3 or more. Safety was an issue with some patients, where the most common adverse effects were hair loss, diarrhea, and fatigue. While less than 1 in 10 participants suffered severe or life-threatening adverse effects, 4 patients died during the trial and 3 more discontinued their participation. The most common severe adverse effects were anemia and neutropenia, a low count of neutrophils, a type of white blood cells that fight infections.
Patients were able to continue sacituzumab govitecan treatments for median of 5.1 months, compared to 2.5 months for earlier therapies. Among the participants, one-third of the group (36 of 108, 33%) responded to the treatments, either complete or partial responses. Half or more of the patients survived with no progression of their disease for about 6 months, while half or more of participants reported overall survival after treatment of 13 to almost 14 months.
Kevin Kalinsky, a cancer specialist at Columbia University medical school and senior author of the paper, says in a university statement, “We saw significant tumor shrinkage with the drug, and it took longer for the cancer to progress compared to other drugs commonly used to treat metastatic triple-negative breast cancer.” Kalinksy adds, “Having smaller tumors can be incredibly meaningful to a patient’s quality of life. When tumors shrink, patients are more likely to experience improvement in symptoms, like pain.”
Immunomedics and this drug have a complex history. The company originally licensed the drug, then code-named IMMU-132, to biopharmaceutical company Seattle Genetics in February 2017 in a deal with a potential value of more than $2 billion. Almost immediately, some Immunomedics investors objected to the deal, leading to a lawsuit, temporary restraining order, and delays in implementing the agreement. By May 2017, as reported by Science & Enterprise, Seattle Genetics had enough and canceled the deal, leading to the resignations of Immunomedics’s founder and CEO. The company’s chief financial officer stayed on and raised $125 million in a private stock sale to finance continued development of IMMU-132, including the clinical trial reported today.
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