7 July 2021 - - The US Food and Drug Administration has approved an expanded label for Keytruda, US-based pharmaceutical company Merck's (NYSE: MRK) anti-PD-1 therapy, as monotherapy for the treatment of patients with locally advanced cutaneous squamous cell carcinoma that is not curable by surgery or radiation, the company said.

This approval is based on data from the second interim analysis of the Phase 2 KEYNOTE-629 trial, in which Keytruda demonstrated an objective response rate of 50% (95% CI, 36-64), including a complete response rate of 17% and a partial response rate of 33% in the cohort of patients with locally advanced disease.

Among the 27 responding patients, 81% had a duration of response of six months or longer, and 37% had a DOR of 12 months or longer.

In June 2020, Keytruda was granted its first indication in cSCC, as monotherapy for the treatment of patients with recurrent or metastatic disease that is not curable by surgery or radiation.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue and can affect more than one body system simultaneously.

Immune-mediated adverse reactions can occur at any time during or after treatment with Keytruda, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, dermatologic reactions, solid organ transplant rejection, and complications of allogeneic hematopoietic stem cell transplantation. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated adverse reactions.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of Keytruda. Based on the severity of the adverse reaction, Keytruda should be withheld or permanently 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. For more information, see "Selected Important Safety Information" below.

The approval was based on data from KEYNOTE-629 (ClinicalTrials.gov, NCT03284424), a multicenter, multi-cohort, non-randomized, open-label trial that enrolled patients with recurrent or metastatic cSCC or locally advanced cSCC. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression.

Patients received Keytruda 200 mg intravenously every three weeks until documented disease progression, unacceptable toxicity or a maximum of 24 months.

Patients with initial radiographic disease progression could receive additional doses of Keytruda during confirmation of progression unless disease progression was symptomatic, rapidly progressive, required urgent intervention, or occurred with a decline in performance status.

Assessment of tumor status was performed every six weeks during the first year and every nine weeks during the second year.

The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Among the 54 patients with locally advanced cSCC treated, the study population characteristics were: median age of 76 years (range, 35 to 95), 80% age 65 or older; 72% male; 83% white, 13% race unknown; 41% Eastern Cooperative Oncology Group performance status of 0 and 59% ECOG PS of 1.

Twenty-two percent received one or more prior lines of therapy; 63% received prior radiation therapy.

The ORR was 50% (95% CI, 36-64), including a complete response rate of 17% and a partial response rate of 33%, for patients treated with Keytruda.

After a median follow-up of 13.4 months, the median DOR had not yet been reached (range, 1.0+ to 17.2+ months).

Among the 27 responding patients, 81% had a DOR of six months or longer, and 37% had a DOR of 12 months or longer.

Among the 159 patients with advanced cSCC (recurrent or metastatic or locally advanced disease) enrolled in KEYNOTE-629, the median duration of exposure to Keytruda was 6.9 months (range, 1 day to 28.9 months).

Adverse reactions occurring in patients with recurrent or metastatic cSCC or locally advanced cSCC were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer treated with Keytruda as a single agent. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence included lymphopenia and decreased sodium.

Keytruda is an anti-programmed death receptor-1 therapy that works by increasing the ability of the body's immune system to help detect and fight tumor cells. Keytruda is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Merck has the industry's largest immuno-oncology clinical research program. There are currently more than 1,500 trials studying Keytruda across a wide variety of cancers and treatment settings.

The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient's likelihood of benefitting from treatment with Keytruda, including exploring several different biomarkers.