General Information

Keytruda (pembrolizumab) is a programmed death receptor-1 (PD 1)-blocking, humanized monoclonal antibody.

Keytruda is specifically approved for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma.

Keytruda is supplied as a solution for intravenous administration. The recommended dose of Keytruda for Merkel cell carcinoma in adults is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression. The recommended dose of Keytruda in pediatric patients is 2 mg/kg (up to a maximum of 200 mg), administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity, or up to 24 months in patients without disease progression.

Clinical Results

FDA Approval

This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials.

The efficacy of Keytruda was investigated in KEYNOTE-017, a multicenter, nonrandomized, open-label trial that enrolled 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease. Patients received Keytruda 2 mg/kg every 3 weeks until unacceptable toxicity or disease progression that was symptomatic, rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at least 4 weeks later with repeat imaging. Patients without disease progression were treated for up to 24 months. Assessment of tumor status was performed at 13 weeks followed by every 9 weeks for the first year and every 12 weeks thereafter. The major efficacy outcome measures were ORR and duration of response as assessed by BICR per RECIST v1.1. The overall tumor response rate was 56%. The median duration was response was not reached. Twenty seven patients (96%) had a duration ≥6 months, while 15 patients (54%) had a duration ≥12 months.

Mechanism of Action

Keytruda (pembrolizumab) is a programmed death receptor-1 (PD 1)-blocking, humanized monoclonal IgG4 kappa antibody. Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors. Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response.