The FDA has approved Keytruda, Merck’s anti-PD-1 therapy, in both three and six week dosing options as monotherapy for the treatment of patients with recurrent or metastatic cutaneous squamous cell carcinoma (cSCC) that is not curable by surgery or radiation. This approval is based on data from the Phase 2 KEYNOTE-629 trial, in which Keytruda demonstrated meaningful efficacy and durability of response, with an objective response rate (ORR) of 34% (95% CI, 25-44), including a complete response rate of four percent and a partial response rate of 31 percent. Among responding patients, 69% had ongoing responses of six months or longer. After a median follow-up time of 9.5 months, the median duration of response (DOR) had not been reached (range, 2.7 to 13.1+ months).

“Cutaneous squamous cell carcinoma is the second most common form of skin cancer,” said Dr. Jonathan Cheng, vice president, clinical research, Merck Research Laboratories. “In KEYNOTE-629, treatment with Keytruda resulted in clinically meaningful and durable responses. Today’s approval is great news for patients with cSCC and further demonstrates our commitment to bringing new treatment options to patients with advanced, difficult-to-treat cancers.”

About the Study

The efficacy of Keytruda was investigated in patients with recurrent or metastatic cSCC enrolled in KEYNOTE-629 (NCT03284424), a multi-center, multi-cohort, non-randomized, open-label trial. The trial excluded patients with autoimmune disease or a medical condition that required immunosuppression. The major efficacy outcome measures were ORR and DOR as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1, modified to follow a maximum of 10 target lesions and a maximum of five target lesions per organ.

Among the 105 patients treated, 87 percent received one or more prior lines of therapy and 74 percent received prior radiation therapy. Forty-five percent of patients had locally recurrent only cSCC, 24 percent had metastatic only cSCC and 31 percent had both locally recurrent and metastatic cSCC. The study population characteristics were: median age of 72 years (range, 29 to 95); 71 percent age 65 or older; 76 percent male; 71 percent White; 25 percent race unknown; 34 percent Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 and 66% ECOG PS of 1.

Keytruda demonstrated an ORR of 34 percent (95% CI, 25-44) with a complete response rate of  four percent and a partial response rate of 31 percent. Among the 36 responding patients, 69 percent had ongoing responses of six months or longer. After a median follow-up time of 9.5 months, the median DOR had not been reached (range, 2.7 to 13.1+ months).

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.

Among the 105 patients with cSCC enrolled in KEYNOTE-629, the median duration of exposure to Keytruda was 5.8 months (range, 1 day to 16.1 months). Patients with autoimmune disease or a medical condition that required systemic corticosteroids or other immunosuppressive medications were ineligible. Adverse reactions occurring in patients with cSCC were similar to those occurring in 2,799 patients with melanoma or non-small cell lung cancer (NSCLC) treated with KEYTRUDA as a single agent. Laboratory abnormalities (Grades 3-4) that occurred at a higher incidence included lymphopenia (11 percent).

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