SMR 2014: More Good News on Pembrolizumab for Melanoma Patients Without Other Options

Source:, November 2014

Results of a head-to-head comparison of pembrolizumab and standard chemotherapy in patients with advanced melanoma, including those who had experienced disease progression following ipilimumab, showed superior clinical response with pembrolizumab that was durable.

The findings of the KEYNOTE-002 study presented Sunday at the Society for Melanoma Research (SMR) 2014 International Congress marked another important result for pembrolizumab. Marketed as Keytruda by Merck, the monoclonal antibody targeting PD-1 received accelerated FDA approval in early September for patients with metastatic melanoma whose disease has progressed on prior therapies.1

Adil Daud, MD, of the University of California at San Francisco, underscored that limited treatment options are available for patients with melanoma whose disease has progressed on ipilimumab or BRAF inhibitors.

In the 3-arm phase 2 study, patients received pembrolizumab at 2 mg/kg (n = 180), 10 mg/kg (n = 181), or chemotherapy (n = 179). At 6 months, the progression-free survival (PFS) rates were 34% and 38% for the 2 mg/kg and 10 mg/kg doses, respectively. Compared with chemotherapy, the lower dose demonstrated a 43% improvement in PFS and the 10 mg/kg dose showed a 50% improvement. The study was designed with co-primary endpoints to assess PFS and overall survival (OS). OS data are anticipated in 2015.2

Given the response rates with pembrolizumab, Dr Daud called this a “highly positive study.” He noted that no significant difference was noted in response between the 2 dose levels. Of note, he said, patients who stayed on pembrolizumab for a longer time showed lower toxicity. No Grade 4 adverse events were seen.

He pointed out that the overall response rate was 5 to 6 times higher with pembrolizumab over chemotherapy. “The benefit from pembrolizumab was seen regardless of BRAF status,” Dr Daud said.

Pembrolizumab is a highly selective humanized monoclonal IgG4 antibody directed against the PD-1 receptor on the cell surface. The drug blocks the PD-1 receptor, preventing binding and activation of PD-L1 and PD-L2. This mechanism causes the activation of T-cell mediated immune responses against tumor cells.

Multiple clinical trials are currently underway exploring pembrolizumab across a variety of tumor types, including a phase 2 and 3 study investigating the agent for advanced melanoma. At this point, over 30 studies are exploring the drug.2


1. FDA approves Keytruda for advanced melanoma [press release]. Silver Spring, MD: FDA newsroom; September 4, 2014.
2. Inman S. Pembrolizumab improves PFS ORR versus chemotherapy in Phase II melanoma study. Onclive. Published November 16, 2014.

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