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Combined immunotherapy shows promising results against advanced melanoma

June 02, 2013
by Helen Dodson

Read this article on Yale News

Combining two cancer immunotherapy drugs in patients with advanced melanoma produced rates of tumor regression that appeared greater than in prior trials with either drug alone. Data from this Phase 1 clinical trial are being formally presented at the 2013 annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago. The abstract was made public by ASCO in advance of the meeting.

Researchers from Memorial Sloan-Kettering Cancer Center (lead author Jedd Wolchok, M.D., Ph.D.), and Yale Cancer Center (senior author Mario Sznol, M.D.), discussed the safety and activity of combining two immune stimulating antibodies — nivolumab (anti-PD-1) and ipilimumab (anti-CTLA-4, Yervoy) — in treating advanced melanoma. Ipilimumab alone is known to prolong survival and produce durable tumor regressions in some patients, and nivolumab also produced durable tumor regression in a subset of advanced melanoma patients in an early-phase clinical trial. However, combining them produced rapid and deep tumor regressions in approximately 30% of patients, a result that was not observed before with either drug administered individually.

Both CTLA-4 and PD-1 are targets for cancer immunotherapy because they shut down the immune system’s ability to respond to foreign invaders. Antibodies blocking PD-1 or CTLA-4 take the brakes off the immune system and permit the development of strong immune responses against the cancer. Nivolumab targets the PD-1 receptor on the surface of T-cells, and ipilimumab targets the CTLA-4 receptors. Both nivolumab and ipilimumab are manufactured by Bristol Myers Squibb.

Researchers provided data for 86 patients in this Phase 1 trial. They report that responses were generally durable, even in patients whose treatment was terminated early.

According to Sznol, clinical research leader of the melanoma program at Yale Cancer Center, this early success in combining drugs will pave the way for large-scale combination immunotherapy trials. “After many years, we are finally realizing the promise of immunotherapy in providing real and durable benefit for advanced cancer patients. Although this trial was focused on melanoma, the combination will be studied in other cancer types. This is only one of many combinations of agents that will likely lead to even more significant advances in cancer treatment,” Sznol said.

The first author on this study was Jedd Wolchok, M.D., Ph.D., of the Ludwig Center for Cancer Immunotherapy at Memorial Sloan-Kettering Cancer Center. Other authors are Harriet Kluger, M.D., Kathleen Reed, Matthew Burke, and Anne Caldwell of Yale School of Medicine and Yale Cancer Center; Margaret Callahan. M.D., Michael Postow, M.D., Naiyer Rizvi, M.D., Alexander Lesokhin, M.D., Neil Segal, M.D., Charlotte Ariyan, M.D., Ruth-Ann Gordon, Stephanie Kronenberg, and Blessing Agunwamba of Memorial Sloan-Kettering Cancer Center; Xiaoling Zhang of Dako North America; and Israel Lowy, M.D., Hector David Inzunza, M.D., William Feely, Christine Horak, Quan Hong, Alan Korman, John Wiggington, M.D., and Ashok Gupta, M.D. of Bristol-Myers Squibb.

The study was funded by Bristol-Myers Squibb Inc. and Ono Pharmaceutical Company Ltd.

Submitted by Renee Gaudette on June 03, 2013