Additional Interim Data for Lambrolizumab Show Survival Benefit for Patients With Advanced Melanoma
Additional data for the investigational anti–PD-1 immunotherapy lambrolizumab (MK-3475) were presented yesterday at the 10th International Congress of the Society for Melanoma Research in Philadelphia. In patients with advanced melanoma, lambrolizumab demonstrated an estimated 1-year overall survival rate of 81% across all monotherapy doses evaluated.
This additional analysis provides approximately 5 months of follow-up for objective response rate beyond the interim results for lambrolizumab from the 135 patients in the advanced melanoma cohort presented at the 2013 ASCO Annual Meeting and published in the The New England Journal of Medicine. This is the first time overall survival data have been presented from the cohort of 135 patients with advanced melanoma enrolled in the ongoing phase IB PN 001 trial for lambrolizumab.
“New agents are needed for patients with advanced melanoma,” said Caroline Robert, MD, PhD, Head of Dermatology at Gustave Roussy, Cancer Campus, Grand Paris. “I am excited by the results seen for [lambrolizumab] to date as a single agent and believe these findings support further study both as a monotherapy and in combination in various solid tumors.”
PN 001 Trial
PN 001 is an ongoing multicenter, single-arm, open-label phase IB study evaluating lambrolizumab monotherapy in more than 1,000 patients with diverse late-stage cancers, predominantly lung and melanoma. Three dosing regimens of lambrolizumab were evaluated including 10 mg/kg every 2 weeks, 10 mg/kg every 3 weeks, or 2 mg/kg every 3 weeks. The primary endpoint of the study is overall response rate, and the secondary endpoints are progression-free survival and overall survival as measured by immune-related response criteria and centrally evaluated RECIST criteria.
The objective response rate across all doses improved with longer duration of follow-up; at the time of this analysis, the objective response rate was 41% (95% confidence interval [CI] = 32%–51%) per RECIST 1.1 criteria compared with the previously reported objective response rate of 38% (95% CI = 25%–44%).
While the majority of responses to lambrolizumab treatment occurred early (within the first 12 weeks), responses and changes from partial to complete response continued to occur after 6 months of treatment. Partial and complete responses occurred as late as 48 and 70 weeks. Of these patients experiencing partial or complete response, 88% showed no evidence of disease progression. Similar response rates were observed between ipilimumab (Yervoy)-pretreated and ipilimumab-naive patients.
At this analysis, the maximum ongoing duration of response recorded was 65 weeks (range 8+ to 65+). The disease control rate across doses for patients in the melanoma cohort was 61% (95% CI = 52%–70%) and median progression-free survival at time of analysis was 36 weeks. Median duration of response and median overall survival have yet to be reached for any dose evaluated.
The rates of treatment-related adverse events were consistent with those previously observed and included fatigue (37%), pruritus (26%), rash (22%), diarrhea (21%), arthralgia (17%), vitiligo (14%), headache (13%), nausea (12%), asthenia (11%), myalgia (11%), and AST increase (10%). Grade 3 to 4 treatment-related adverse events that occurred in more than one patient were AST increase, fatigue, rash and renal failure (n = 2 each).
Future Trials
A phase II registration trial (PN 002) comparing two doses of lambrolizumab vs chemotherapy in patients with advanced melanoma that has progressed after prior therapy has completed enrollment, and a phase III registration trial of lambrolizumab vs ipilimumab in ipilimumab-naive patients with advanced melanoma is ongoing. Merck plans to initiate combination trials this year and in early 2014 in melanoma and other cancers.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
