Interim Data for MK-3475 Shows Expanded Benefit in Advanced Melanoma

These survival findings were the first from the ongoing trial, which also showed that 41% of patients enrolled in the study saw tumor shrinkage. The phase Ib PN 001 trial is a single-arm, open-label study evaluating MK-3475 monotherapy in more than 1000 patients with diverse late-stage cancers.

"New agents are needed for patients with advanced melanoma," Caroline Robert, MD, head of Dermatology at Gustave Roussy, Cancer Campus, Grand Paris, said in a press release. "I am excited by the results seen for MK-3475 to date as a single agent and believe these findings support further study both as a monotherapy and in combination in various solid tumors."

The study enrolled 135 patients with advanced melanoma. In the dose finding trial, patients received MK-3475 at 10mg/kg every 2 weeks, 10mg/kg every 3 weeks or 2mg/kg every 3 weeks.

The objective response rate (ORR) across all doses improved with longer duration of follow-up. At the time of the analysis, the ORR was 41% with a 9% complete response rate, as evaluated by a blinded central review committee using RECIST 1.1 criteria. The previously reported ORR across all doses was 38% (CI 95%; 25% to 44%; per RECIST criteria).

The majority of responses to MK-3475 treatment occurred within the first 12 weeks, but changes from partial to complete response continued to occur after 6 months of treatment and as late as 48 and 70 weeks.

Treatment-related adverse events rates 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—4 treatment-related adverse events that occurred in more than one patient were AST increase, fatigue, rash and renal failure (n = 2 each).

Median duration of response and median overall survival have yet to be reached for any dose evaluated.

"These results provide further insight into the therapeutic properties of MK-3475 in patients with advanced melanoma," Roger M. Perlmutter, MD, president of Merck Research Laboratories, said in a press release. Merck is the company developing the drug."Simply put, our data make us hopeful that this novel investigational therapy could potentially provide meaningful benefits to patients suffering from this malignant disease."

MK-3475, a monoclonal IgG4 antibody, is in a class of agents that target PD-1, an inhibitory T-cell co-receptor. It is designed to restore the natural ability of the immune system to recognize and target cancer cells by selectively achieving dual ligand blockade (PD-L1 and PD-L2) of the PD-1 protein.Blocking the PD-1 protein enables activation of the immune system¹s T-cells that target cancer by essentially releasing a brake on the immune system.

In April 2013, MK-3475 received Breakthrough Therapy Designation by the FDA for the treatment of patients with advanced melanoma.