Keytruda (pembrolizumab) is a programmed death receptor-1 (PD-1)-blocking antibody.
Keytruda is specifically indicated as monotherapy for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) [≥10 mutations/megabase (mut/Mb)] solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options.
Keytruda is supplied as an injection for intravenous administration. The recommended dose for TMB-H Cancer is 200 mg every 3 weeks or 400 mg every 6 weeks for adults; 2 mg/kg (up to 200 mg) every 3 weeks for pediatrics. Administer Keytruda as an intravenous infusion over 30 minutes.
The FDA approved Keytruda for TMB-H cancer 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 accelerated approval was based on data from a prospectively-planned retrospective analysis of 10 cohorts (A through J) of patients with various previously treated unresectable or metastatic solid tumors with TMB-H, who were enrolled in KEYNOTE-158, a multicenter, non-randomized, open-label trial evaluating Keytruda (200 mg every three weeks). The trial excluded patients who previously received an anti-PD-1 or other immune-modulating monoclonal antibody, or who had an autoimmune disease, or a medical condition that required immunosuppression. Tumor response was assessed every nine weeks for the first 12 months and every 12 weeks thereafter. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) in the patients who received at least one dose of Keytruda 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.
In KEYNOTE-158, 1,050 patients were included in the efficacy analysis population. TMB was analyzed in the subset of 790 patients with sufficient tissue for testing based on protocol-specified testing requirements. Of the 790 patients, 102 (13%) had tumors identified as TMB-H, defined as TMB ≥10 mut/Mb.
In the 102 patients whose tumors were TMB-H, Keytruda demonstrated an ORR of 29%, with a complete response rate of 4% and a partial response rate of 25%. After a median follow-up time of 11.1 months, the median DOR had not been reached. Among the 30 responding patients, 57% had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer.
In a pre-specified analysis of patients with TMB ≥13 mut/Mb (n=70), Keytruda demonstrated an ORR of 37%, with a complete response rate of 3% and a partial response rate of 34%. After a median follow-up time of 11.1 months, the median DOR had not been reached. Among the 26 responding patients, 58% had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer. In an exploratory analysis in 32 patients whose cancer had TMB ≥10 mut/Mb and <13 mut/Mb, the ORR was 13%, including two complete responses and two partial responses.
Adverse effects associated with the use of Keytruda may include, but are not limited to, the following:
For additional information regarding Keytruda or TMB-H cancer, please visit the Keytruda website.