Lambrolizumab (previously known as MK-3475) is a humanized monoclonal immunoglobulin G4 antibody that blocks the programmed death 1 (PD-1) receptor and reactivates an immune response to the cancer cells. The PD-1 receptor limits the body’s immune response against cancer. Researchers have set out to investigate the safety and antitumor activity of 3 dosing regimens of lambrolizumab in a cohort of patients with advanced melanoma (Hamid O, et al. N Engl J Med. 2013;369:134-144).
This multi-institutional, international, phase 1 expansion study included 135 patients with advanced melanoma. Patients who had or had not received treatment with the checkpoint inhibitor ipilimumab were administered the intravenous PD-1 inhibitor lambrolizumab at 10 mg/kg every 2 or 3 weeks or 2 mg/kg every 3 weeks. Tumor responses were assessed every 12 weeks.
The most common adverse events reported with lambrolizumab in this study were fatigue, rash, pruritus, and diarrhea; most of the adverse events were low grade. Drug-related adverse events of any grade were reported by 79% of the patients, with grade 3 or 4 adverse events reported by 13%. The highest incidence of overall treatment-related adverse events was seen among patients receiving the lambrolizumab dose of 10 mg/kg every 2 weeks compared with patients receiving the 10-mg/kg dose every 3 weeks and those receiving 2 mg/kg every 3 weeks (23% vs 4% and 9%, respectively).
The confirmed response rate across the 3 dose cohorts was 38% (95% confidence interval [CI], 25-44), with the highest confirmed response rate observed in the patients receiving the 10- mg/kg dose of lambrolizumab every 2 weeks (52%; 95% CI, 38-66). Previous therapy with ipilimumab did not affect the response to lambrolizumab. The response rate among patients who were previously treated with ipilimumab was 38% (95% CI, 23-55) compared with 37% (95% CI, 26-49) among those who had not received treatment previously. Response rates were durable in the majority of patients who had experienced response at a median follow-up of 11 months; 81% of patients with a response were still continuing treatment as of March 2013. The overall median progression-free survival among the 135 patients was longer than 7 months.
For patients with advanced or progressing melanoma, these findings suggest that treatment with lambrolizumab can result in a high rate of tumor regression, and only limited toxic effects of mainly grade 1 or grade 2.
