Keytruda (pembrolizumab)

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

Company:

Approval Status:

Approved September 2014

Specific Treatments:

unresectable or metastatic melanoma

Therapeutic Areas

Find Related Trials for The Following Conditions

General Information

Keytruda (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.

Keytruda is specifically indicated for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor.

Keytruda is supplied as a solution for intravenous infusion. The recommended dose is 2 mg/kg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression or unacceptable toxicity.

Clinical Results

FDA Approval

Keytruda for the treatment of patients with unresectable or metastatic melanoma and disease progression following ipilimumab and, if BRAF V600 mutation positive, a BRAF inhibitor was approved under accelerated approval based on tumor response rate and durability of response. An improvement in survival or disease-related symptoms has not yet been established. Continued approval for this indication may be contingent upon verification and description of clinical benefit in the confirmatory trials. 

The efficacy was Keytruda was evaluated in an open label, randomized, comparative dose trial in subjects with unresectable or metastatic melanoma with progression of disease; refractory to two or more doses of ipilimumab (3 mg/kg or higher) and, if BRAF V600 mutation-positive, a BRAF or MEK inhibitor; and disease progression within 24 weeks following the last dose of ipilimumab.  The subjects were randomized to receive 2 mg/kg (n=89) or 10 mg/kg (n=84) of Keytruda every 3 weeks until unacceptable toxicity or disease progression that was symptomatic, was rapidly progressive, required urgent intervention, occurred with a decline in performance status, or was confirmed at 4 to 6 weeks with repeat imaging. Assessment of tumor status was performed every 12 weeks. The major efficacy outcome measures were confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as assessed by blinded independent central review and duration of response. The ORR was 24% (95% confidence interval: 15, 34) in the 2 mg/kg arm, consisting of 1 complete response and 20 partial responses. Among the 21 subjects with an objective response, 3 (14%) had progression of disease 2.8, 2.9, and 8.2 months after initial response. The remaining 18 subjects (86%) had ongoing responses with durations ranging from 1.4+ to 8.5+ months, which included 8 subjects with ongoing responses of 6 months or longer. One additional subject developed two new asymptomatic lesions at the first tumor assessment concurrent with a 75% decrease in overall tumor burden; Keytruda was continued and this reduction in tumor burden was durable for 5+ months. There were objective responses in subjects with and without BRAF V600 mutation-positive melanoma. Similar ORR results were observed in the 10 mg/kg arm. 

Side Effects

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

  • fatigue
  • cough
  • nausea
  • pruritus
  • rash
  • decreased appetite
  • constipation
  • arthralgia
  • diarrhea

Mechanism of Action

Keytruda (pembrolizumab) is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. 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 unresectable or metastatic melanoma, please visit www.keytruda.com