Currently Enrolling Trials
Keytruda (pembrolizumab) is a programmed death receptor-1 (PD 1)-blocking, humanized monoclonal antibody.
Keytruda is specifically indicated for the treatment of patients with metastatic SCLC with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. Merck voluntarily withdrew this approval in March of 2021 after a post-marketing study failed to reach both primary endpoints, a contingency for full approval.
Keytruda is supplied as an injection for intravenous administration. The recommended dose is 200 mg every 3 weeks.
The FDA granted accelerated approval to Keytruda for this indication based on tumor response rate and durability of response data from KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1). Full approval is contingent on completing a post-marketing evaluation demonstrating the superiority of Keytruda to other products in extending overall survival (OS).
KEYNOTE-158 (cohort G) and KEYNOTE-028 (cohort C1) were both multicenter, multi-cohort, non-randomized, open-label trials evaluating Keytruda in patients with SCLC who had disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy. The trials excluded patients with autoimmune disease or a medical condition that required immunosuppression. Among the 83 patients enrolled in the trials and who were evaluated for efficacy, 64% received two prior lines of therapy and 36% received three or more lines of therapy; 60% received prior thoracic radiation therapy; 51% received prior radiation therapy to the brain.
Patients evaluated for efficacy received either Keytruda 200 mg intravenously every three weeks (n=64) or 10 mg/kg intravenously every two weeks (n=19). Treatment with Keytruda continued 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, was rapidly progressive, required urgent intervention or occurred with a decline in performance status. The major efficacy outcome measures were objective response rate (ORR) and duration of response (DOR) as assessed by 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.
Keytruda demonstrated an ORR of 19%, with a complete response rate of 2% and a partial response rate of 17%. Among the 16 responding patients, 94% had a DOR of six months or longer, 63% had a DOR of 12 months or longer and 56% had a DOR of 18 months or longer. Responses ranged from 4.1 to 35.8+ months.
In January 2020, KEYNOTE-604, the confirmatory Phase III trial required for continued approval, hit one of the dual primary endpoints, progression-free survival (PFS), but didn’t reach statistical significance for the other primary endpoint of OS. Merck will voluntarily withdraw the U.S. indication for Keytruda for the treatment of patients with metastatic small cell lung cancer (SCLC) with disease progression on or after platinum-based chemotherapy and at least one other prior line of therapy.
Adverse effects associated with the use of Keytruda for small cell lung cancer may include, but are not limited to, the following:
- musculoskeletal pain
- decreased appetite
- 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.
For additional information regarding Keytruda or previously treated metastatic small cell lung cancer, please visit the Keytruda website.