CHICAGO -- An investigational immune therapy was safe and well tolerated in patients with advanced melanoma, a researcher reported here.
In addition, lambrolizumab had a 38% response rate and several patients saw their tumors disappear, according to Antoni Ribas, MD, PhD, of the Jonsson Comprehensive Cancer Center at the University of California Los Angeles.
The drug, which is aimed at reviving the immune response to cancer, also appeared to yield long-lasting responses, Ribas reported at the annual meeting of the American Society of Clinical Oncology and online in the New England Journal of Medicine.
The drug is the second entry in a class that is attracting increasing interest, namely blockade of the PD-1/PD-L1 immune checkpoint, which renders tumor cells immune to the attack of activated T cells.
PD-1, on the surface of killer T cells, is activated by a corresponding molecule, PD-L1, on the surface of tumor cells, with the effect of turning off the immune response to the cancer.
In essence, the T cells are muzzled so that they cannot attack the tumor.
Earlier, researchers reported here that the first entrant in the field, nivolumab, also had a good safety profile and durable responses among patients with advanced melanoma.
Taken together, the results show "the effectiveness of this approach in patients with advanced melanoma," commented Lynn Schuchter, MD, of the University of Pennsylvania in Philadelphia, a melanoma expert who speaks on the topic for ASCO.
Time will tell whether the drugs have different properties, if one is better than another, and if so in what patients, she told MedPage Today. But she called the PD-1 approach a "remarkable advance" for melanoma patients.
The PD-1 immune checkpoint can also be attacked from the other side, and drugs are under development that block the PD-L1 molecule on tumor cells.
Ribas and colleagues tested lambrolizumab in a large international multi-center phase I trial, aimed at establishing the safety and tolerability of the drug in several dosing regimens -- 10 mg per kg body weight every 2 or 3 weeks or 2 mg/kg every 3 weeks.
They included 135 patients with advanced disease, including those who had been previously treated with the immune checkpoint inhibitor ipilimumab (Yervoy) and those who had not.
The researchers also assessed tumor responses every 12 weeks, Ribas and colleagues reported.
Overall, the drug had on limited toxicity; common adverse events attributed to the drug included fatigue, rash, pruritus, and diarrhea, but most of the adverse events were grades 1 and 2.
Remarkably, however, the overall objective response rate, confirmed by radiology, was 38% across all dose cohorts, and 52% in the 52 patients who received the highest dose of 10 mg/kg every 2 weeks.
Moreover, responses were durable -- 42 of the 52 patients who responded were still on treatment when the data were analyzed in March 2013.
Overall, the median progression-free survival among the 135 patients was longer than 7 months.
Prior exposure to ipilimumab had no effect on the benefit of the therapy, Ribas and colleagues reported.
"The striking anticancer activity observed with lambrolizumab requires confirmation in larger studies," they wrote.
The study was supported by by Merck Sharp and Dohme. Ribas reported financial links with Merck, as well as with Amgen, GlaxoSmithKline, Novartis, Roche, and MedImmune.
Michael Smith
North American Correspondent
North American Correspondent for MedPage Today, is a three-time winner of the Science and Society Journalism Award of the Canadian Science Writers' Association. After working for newspapers in several parts of Canada, he was the science writer for the Toronto Star before becoming a freelancer in 1994. His byline has appeared in New Scientist, Science, the Globe and Mail, United Press International, Toronto Life, Canadian Business, the Toronto Star, Marketing Computers, and many others. He is based in Toronto, and when not transforming dense science into compelling prose he can usually be found sailing.
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