Preliminary data from an ongoing Phase IB expansion study presented at ASCO's annual meeting and published in the NEJM demonstrated that Merck & Co.'s experimental anti-PD-1 antibody lambrolizumab, also known as MK-3475, helped reduce the size of tumours in patients with advanced melanoma. Merck Research Laboratories president Roger Perlmutter said that "based on these data and additional findings from our ongoing studies, Merck plans to initiate late-stage clinical trials of lambrolizumab in advanced melanoma, and non-small-cell lung cancer in the third quarter of 2013." If the therapy proves successful, the company could file for regulatory approval in 2015.
Lambrolizumab obtained breakthrough therapy status from the FDA in April. In the study, 135 patients with advanced melanoma were administered one of three dosing regimens of lambrolizumab until disease progression or unacceptable toxicity. The regimens included two 10-milligram doses, one given every two weeks and the other every three weeks, and a 2-milligram dose administered every three weeks. Tumour response was assessed every 12 weeks by an independent radiographic review.
Merck said the interim overall confirmed response rate for lambrolizumab treatment was 38 percent across all dosing regimens, with the highest overall response rate measuring 52 percent in the 10-milligram every two weeks dosing regimen. Ten percent of patients in this dose group were complete responders, the company added. The duration of confirmed responses after the first 12-week evaluation ranged from greater than 28 days to up to more than 8 months at the time of the analysis. Gary Gilliland, head of oncology research at Merck, said 80 percent of responding patients were continuing treatment at the time of data analysis in March. Merck noted that the median duration of response had not been reached with a median follow-up time of 11 months. Merck has not yet reported overall survival data for lambrolizumab.
The most common treatment-related adverse events included fatigue, rash, pruritus and diarrhea, but most were of modest severity, according to the researchers. The dosing regimen that triggered the highest response rate also had the highest incidence of treatment-related adverse events. Lead researcher Antoni Ribas noted that 13 percent of patients had more serious side effects, including inflammation of the lung or kidney, and thyroid problems.
Gilliland noted that "we continue to make significant progress in our clinical development programme for lambrolizumab in multiple indications." Merck plans to study the drug in patients with advanced melanoma who did not improve following treatment with Bristol-Myers Squibb's Yervoy (ipilimumab), which works by a different mechanism than blocking PD-1. The company also plans to evaluate lambrolizumab in various combinations with other drugs, including chemotherapy and other immunotherapies, as well as agents that target certain molecular features of tumours, Gilliland added.
Separately, Bristol-Myers Squibb presented early-stage data at the ASCO meeting regarding its anti-PD-1 antibody nivolumab for advanced melanoma, in which the overall response rate was 31 percent. Further, the overall response rate was 41 percent among a subset of patients given a particular dose that will be tested in subsequent trials.
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