The Food and Drug Administration has granted an accelerated approval to pembrolizumab, a PD-1 inhibitor, for the treatment of patients with advanced or unresectable melanoma that is no longer responding to other drugs.
Pembrolizumab (Keytruda; Merck) is intended for use following treatment with ipilimumab. For BRAF V600-positive patients, the drug should be used after treatment with both ipilimumab and a BRAF inhibitor, according to an FDA press statement.
The approved dose is 2 mg/kg every 3 weeks for patients with unresectable or metastatic melanoma and disease progression following the initial treatments.
According to a Merck press statement, "This indication is approved ... based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established." Additional studies are underway, and continued approval may be contingent upon verification and description of clinical benefit in the confirmatory trials, the statement noted.
The pivotal trial comprised 173 clinical trial participants with advanced melanoma whose disease progressed after prior treatment. All participants were treated with pembrolizumab, either at the recommended dose of 2 mg/kg or at a higher dose of 10 mg/kg. In the half of the participants who received pembrolizumab at the recommended dose of 2 mg/kg, approximately 24% had their tumors shrink. This effect lasted at least 1.4-8.5 months and continued beyond this period in most patients, the FDA statement said.
The drug was discontinued for adverse reactions in 6% of 89 patients who received the recommended dose of 2 mg/kg and 9% of 411 patients across all doses studied. Serious adverse reactions occurred in 36% of patients receiving pembrolizumab. The most common serious adverse reactions reported in 2% or more of patients were renal failure, dyspnea, pneumonia, and cellulitis. Adverse reactions occurring in at least 20% of the 411 patients across doses were fatigue (47%), cough (30%), nausea (30%), pruritus (30%), rash (29%), decreased appetite (26%), constipation (21%), arthralgia (20%), and diarrhea (20%).
The FDA cautions that pembrolizumab also has the potential for severe immune-mediated side effects. In the 411 participants with advanced melanoma, severe immune-mediated side effects involving healthy organs, including the lung, colon, hormone-producing glands, and liver, occurred uncommonly, they said.
It is the sixth drug to be approved for melanoma since 2011, joining ipilimumab (2011), peginterferon alfa-2b (2011), vemurafenib (2011), dabrafenib (2013), and trametinib (2013).
The Melanoma Research Alliance applauded FDA’s action in a press statement.
"The news of FDA’s first approval of an anti-PD-1 drug is extremely exciting and shows just how far the field has come in the last few years," said Debra Black, MRA cofounder. "When we started MRA there was little hope for melanoma patients. Today we are seeing a real sea change, with several new therapies and proof of concept that these new treatments can save lives."