Lambrolizumab produced a high rate of sustained tumor regression when tested among 135 patients with advanced melanoma in a multi-institutional, international, phase I expansion study reported in The New England Journal of Medicine. At a median follow-up of 11 months, responses were durable in the majority of patients. Toxic effects were mainly limited to grade 1 or 2.
Previously known as MK-3475, lambrolizumab is an antibody against the programmed death 1 (PD-1) receptor. Patients with advanced melanoma, both those who had received prior treatment with the immune checkpoint inhibitor ipilimumab (Yervoy) and those who had not, were given lambrolizumab intravenously at a dose of 10 mg/kg every 2 or 3 weeks or 2 mg/kg every 3 weeks.
The confirmed response rate across all dose cohorts was 38% (95% confidence interval [CI] = 25–44), with the highest confirmed response rate observed in the 10 mg/kg every 2 weeks cohort (52%; 95% CI = 38–66). “The response rate did not differ significantly between patients who had received prior ipilimumab treatment and those who had not (confirmed response rate = 38% [95% CI = 23–55] and 37% [95% CI = 26–49], respectively),” the investigators observed. Among the responders, 81% (42 of 52) were still receiving treatment at the time of analysis in March 2013.
Drug-related adverse events of any grade were reported by 79% of patients, with grade 3 or 4 adverse events reported by 13%. “Common adverse events attributed to treatment were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade,” the authors reported.
“The cohort with the maximum administered dose of lambrolizumab [10 mg/kg every 2 weeks] showed the highest response rate of 52%. This cohort also showed the highest rate of drug-related adverse events, although this may be due in part to a longer duration of therapy,” the authors wrote.
“Although cross-study comparison of adverse event rates should be viewed with caution, it seems that in comparison to anti-CTLA-4 therapy, lambrolizumab therapy was associated was associated with a lower incidence and a different spectrum of immune-related adverse events, possibly owing to a distinct mechanism of action with a more targeted effort on tumor-specific T cells,” the researchers noted.
“The study was sponsored by Merck Sharpe and Dohme, which provided the study drug and worked closely jointly with the senior academic authors to design the study, collect the data, and interpret the study results,” the authors acknowledged. ■
Hamid O, et al: N Engl J Med 369:134-144, 2013.