Pembrolizumab Approved for Advanced Melanoma
FDA on September 4 announced the approval of pembrolizumab, a humanized programmed death receptor-1 (PD-1)–blocking monoclonal antibody product, for the treatment of advanced melanoma in certain patients.
Labeling (PDF) for the biologic states that it is indicated for use in patients with unresectable or metastatic melanoma whose illness has progressed after treatment with ipilimumab and, if a BRAF-V600 mutation is present in the tumor cells, a BRAF inhibitor.
Merck stated that it plans to make the product available within a week under the brand name Keytruda.
The labeling for pembrolizumab states that the antibody binds to PD-1 receptors on T cells and inhibits their interaction with two ligands that are involved in the suppression of T-cell proliferation and cytokine production.
According to FDA and Merck, pembrolizumab is the first product with this mechanism of action to be approved by the agency. The biologic was classified by FDA as a breakthrough therapy on the basis of preliminary clinical evidence that it may offer a substantial improvement over available treatments.
It is not yet known whether pembrolizumab extends the lives of patients with advanced melanoma.
FDA's determination of pembrolizumab's efficacy was based on the results of a study involving 173 patients with advanced melanoma that had progressed after previous therapy. According to FDA, tumor shrinkage occurred among about a quarter of patients treated with 2- or 10-mg/kg doses of pembrolizumab.
The recommended dosage of pembrolizumab is 2 mg/kg infused intravenously over 30 minutes every three weeks until disease progression or unacceptable toxicity occurs. The labeling includes recommendations for reducing the dosage or discontinuing therapy in response to certain adverse events or laboratory test results.
In clinical trials, the most frequently reported adverse events among pembrolizumab recipients were fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, joint pain, and diarrhea.
Rare but serious adverse events attributed to the immune system-mediating effects of pembrolizumab were reported during clinical trials of the biologic. These adverse events affected healthy organs, including the lung, colon, hormone-producing glands, and liver. The labeling recommends corticosteroid therapy for the management of such events if they occur.
An FDA-required Medication Guide (PDF) for pembrolizumab warns patients that they are at risk for immune system-related adverse events during therapy with the biologic.
Pembrolizumab will be supplied as a lyophilized powder in 50-mg single-use vials that should be refrigerated at 2–8 °C until use. Instructions for reconstituting the vial's contents with Sterile Water for Injection, USP, and subsequent dilution into an i.v. bag containing 0.9% Sodium Chloride Injection, USP, are included in the labeling.