Keytruda (pembrolizumab)

The following drug information is obtained from various newswires, published medical journal articles, and medical conference presentations.

Company:

Approval Status:

Approved September 2017

Specific Treatments:

PD-L1 expressing gastric or gastroesophageal junction adenocarcinoma

Therapeutic Areas

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General Information

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

Keytruda is specifically indicated for patients with recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 [Combined Positive Score (CPS) ≥1] as determined by an FDA-approved test, with disease progression on or after two or more prior lines of therapy including fluoropyrimidine- and platinum-containing chemotherapy and if appropriate, HER2/neu-targeted therapy.

Keytruda is supplied as a solution for intravenous administration. The recommended dose of Keytruda for gastric cancer 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. 

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 FDA approval of Keytruda was based on KEYNOTE-059, a multicenter, non-randomized, open-label multi-cohort trial that enrolled 259 patients with gastric or gastroesophageal junction (GEJ) adenocarcinoma who progressed on at least 2 prior systemic treatments for advanced disease. Previous treatment must have included a fluoropyrimidine and platinum doublet. Patients received Keytruda 200 mg 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 every 6 to 9 weeks. The major efficacy outcome measures were ORR according to RECIST v1.1, modified to follow a maximum of 10 target lesions and a maximum of 5 target lesions per organ, as assessed by blinded independent central review, and duration of response. Among the 259 patients, 55% (n = 143) had tumors that expressed PD-L1. For the 143 patients, the ORR was 13.3%; 1.4% had a complete response and 11.9% had a partial response. Among the 19 responding patients, the duration of response ranged from 2.8+ to 19.4+ months, with 11 patients (58%) having responses of 6 months or longer and 5 patients (26%) having responses of 12 months or longer.

Side Effects

Adverse effects associated with the use of Keytruda may include, but are not limited to, the following:

fatigue

musculoskeletal pain

decreased appetite

pruritus

diarrhea

nausea

rash

pyrexia

cough

dyspnea

constipation

pain

abdominal pain

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. 

Additional Information

For additional information regarding Keytruda or PD-L1 expressing gastric or gastroesophageal junction adenocarcinoma, please visit https://www.keytruda.com/