Pembrolizumab approved for advanced TMB-H solid tumors
medwireNews: Pembrolizumab has been given accelerated approval by the US FDA for the treatment of unresectable or metastatic solid malignancies with a high tumor mutational burden (TMB-H).
The PD-1 inhibitor may be given to adult and pediatric patients who have progressed after initial therapy, have no further treatment options, and show a TMB of 10 mutations/Mb or higher on the simultaneously approved companion diagnostic test.
However, the prescribing information has a “Limitation of Use” reminding physicians that “the safety and effectiveness of pembrolizumab in pediatric patients with TMB-H central nervous system cancers have not been established.”
This latest pembrolizumab approval follows the earlier tumor-agnostic approval for use in solid tumors that are microsatellite instability-high or have mismatch repair deficiency.
The decision is based on a retrospective analysis of data from the multi-tumor KEYNOTE-158 trial, where 29% of 102 TMB-H patients achieved an objective response, with 57% of responses ongoing at 1 year. Data from other cohorts of the study led to pembrolizumab approval for patients with metastatic small-cell lung cancer and those with advanced cervical cancer or primary mediastinal large B-cell lymphoma.
The recommended dose of pembrolizumab for TMB-H adult patients is 200 mg every 3 weeks or 400 mg every 6 weeks until unacceptable toxicity or disease progression, and 2 mg/kg to a maximum of 200 mg every 3 weeks for children.
The most common adverse events (AEs) associated with pembrolizumab include fatigue, musculoskeletal pain, and gastrointestinal side effects, as well as immune-mediated AEs of pneumonitis, colitis, hepatitis, endocrinopathy, nephritis, and skin reactions.
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