Combination of drugs produces dramatic tumor responses in advanced melanoma patients

The combination of the immunotherapy drug ipilimumab and the investigational antibody drug nivolumab led to long-lasting tumor shrinkage in more than half of patients with metastatic melanoma, according to results from a Phase I trial simultaneously published online on Sunday, June 2, in The New England Journal of Medicine and presented by Memorial Sloan-Kettering Cancer Center researchers at the 49th Annual Meeting of the American Society of Clinical Oncology (ASCO).

Several patients experienced of more than 80 percent within 12 weeks of receiving the drugs, and the shrinkage was long lasting. Further, 40 percent of patients who received varying concurrent dosages had an objective response—meaning at least a 50 percent reduction in . Side effects from the drug combination were manageable and often reversible.

"We are very excited about the response rates these patients have experienced. This kind of deep and rapid has never been seen in melanoma using immunotherapy, and suggests that these two drugs could be better used in combination than alone," said Jedd D. Wolchok, MD, PhD. Dr. Wolchok, a medical oncologist at the Ludwig Center for at Memorial Sloan-Kettering, is lead author on The New England Journal of Medicine paper and also presented the findings at ASCO.

Dr. Wolchok and his team combined ipilimumab and nivolumab because promising results in preclinical testing suggested the drugs impact the immune system in a complementary way. By blocking the inhibitory marker CTLA-4, ipilimumab, which the FDA approved for advanced melanoma in 2011, activates the immune system, prompting to start attacking the tumor. Blocking PD-1 further activates T cells in a different manner, allowing them to continue the attack.

"Previous studies had shown that ipilimumab alone could prolong overall survival in advanced melanoma patients, and nivolumab alone could produce durable tumor responses in melanoma and other cancers, so the combination of the two drugs was quite logical and well supported by preclinical and clinical trial data," he said.

However, Dr. Wolchok notes that not all patients respond to immunotherapy and determining why some patients do not is becoming an extremely important part of advancing this field.

Because of the strong Phase I findings, researchers will begin testing the combination this June as a therapy for patients newly diagnosed with advanced melanoma in a randomized Phase III trial led by Memorial Sloan-Kettering and taking place at more than 150 institutions worldwide.

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