21 December 2018 - - The US Food and Drug Administration has approved Keytruda, US-based Merck's (NYSE: MRK) anti-PD-1 therapy, for the treatment of adult and pediatric patients with recurrent locally advanced or metastatic Merkel cell carcinoma, based on the results of the Cancer Immunotherapy Trials Network's CITN-09/KEYNOTE-017 trial, the company said.

In this Phase 2 trial of 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease, Keytruda monotherapy demonstrated an objective response rate of 56% (95% CI, 41-70), with a complete response rate of 24% (95% CI, 13-38) and a partial response rate of 32 % (95% CI, 20-47).

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.

Immune-mediated adverse reactions, which may be severe or fatal, can occur with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation.

Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate.

Keytruda can also cause severe or life-threatening infusion-related reactions. Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman.

The approval was based on data from CITN-09/KEYNOTE-017, a Phase 2, non-randomized, multicenter, open-label trial, initiated and conducted by the Cancer Immunotherapy Trials Network based at the Fred Hutchinson Cancer Research Center and sponsored by the National Cancer Institute, evaluating Keytruda in 50 patients with recurrent locally advanced or metastatic MCC who had not received prior systemic therapy for their advanced disease.

Patients with active autoimmune disease or a medical condition that required immunosuppression were ineligible.

Patients received Keytruda 2 mg/kg every three 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 four 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 nine weeks for the first year and every 12 weeks thereafter.

The major efficacy outcome measures were objective response rate and duration of response as assessed by blinded independent central review per RECIST v1.1.

Among the 50 patients treated, the median age was 71 years (range, 46 to 91 years; 80% age 65 or older); 68% were male; 90% were White; and ECOG performance score was 0 and 1.

Fourteen percent had stage IIIB disease, and 86 % had stage IV.

For patients with local or locoregional disease, 84 % had prior surgery, and 70 % had prior radiation therapy.

In CITN-09/KEYNOTE-017, the ORR was 56% (95% CI, 41-70), with a complete response rate of 24% (95% CI, 13-38) and a partial response rate of 32% (95% CI, 20-47).

Among the responding patients, median DOR was not reached (range, 5.9 to 34.5+ months). Ninety-six percent of responding patients experienced a DOR for six months or longer, and 54 % experienced a DOR for 12 months or longer.

Among the 50 patients with MCC enrolled in CITN-09/KEYNOTE-017, the median duration of exposure to Keytruda was 6.6 months (range, 1 day to 23.6 months).

Adverse reactions occurring in patients with MCC were generally similar to those in patients with melanoma or NSCLC.