Merck has reported positive data from a pivotal Phase II trial (KEYNOTE-002) of its anti-PD-1 therapy pembrolizumab in patients with ipilimumab-refractory advanced melanoma.
Pembrolizumab is a humanised monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2.
The global, randomised Phase II KEYNOTE-002 trial evaluated pembrolizumab at doses of 2mg/kg every three weeks and 10mg/kg every three weeks compared to investigator’s choice chemotherapy (paclitaxel plus carboplatin, paclitaxel, carboplatin, dacarbazine or temozolomide) in these patients.
The trial showed that pembrolizumab improved the primary endpoint of progression-free survival (PFS), compared to chemotherapy.
In the trial, 83% of patients had the most advanced stage of disease (M1c) and 73% of patients had received at least two prior systemic therapies including ipilimumab.
The co-primary endpoints of the trial were PFS and overall survival, while secondary endpoints included overall response rate (ORR), duration of response and safety; and health-related quality of life (HRQoL) as a pre-specified exploratory endpoint.
Merck Research Laboratories vice-president of global clinical development for oncology Dr Eric Rubin said: "These findings demonstrate pembrolizumab was superior to chemotherapy in helping more patients with ipilimumab-refractory advanced melanoma achieve progression-free survival.
"The comparative efficacy and safety data from the pivotal KEYNOTE-002 study validate and extend the findings from our earlier study in these difficult-to-treat patients, and we look forward to sharing data on overall survival at a future congress."
The company said that the objective of the pre-specified analysis was to assess the superiority of either dose of Keytruda over chemotherapy for PFS.
The trial was designed with co-primary endpoints of PFS and overall survival and an evaluation of overall survival is planned at the pre-specified final analysis in 2015.
In a pre-specified analysis for HRQoL, patients treated with pembrolizumab reported a significantly smaller decrement in health status/quality of life score compared to those treated with chemotherapy.
Image: Melanoma in skin biopsy with H&E stain — this case may represent superficial spreading melanoma. Photo: courtesy of KGH.