FDA grants accelerated approval to Keytruda for solid tumors with specific biomarker

The FDA today granted accelerated approval to pembrolizumab for adults and children with unresectable or metastatic, microsatellite instability–high or mismatch repair–deficient solid tumors.

This indication for pembrolizumab (Keytruda, Merck) — the FDA’s first tissue/site-agnostic approval — includes patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, as well as patients with colorectal cancer that has progressed following treatment with fluoropyrimidine, oxaliplatin and irinotecan.

Approximately 5% of patients with metastatic colorectal cancer have microsatellite instability–high or mismatch repair–deficient tumors, which contain abnormalities that hinder the repair of cell DNA. Other than colorectal tumors, these biomarkers are commonly observed in endometrial and other gastrointestinal cancers, and less commonly in cancers of the breast, prostate, bladder, thyroid gland and other sites.

“This is an important first for the cancer community,” Richard Pazdur, MD, acting director of the office of hematology and oncology products in the FDA’s Center for Drug Evaluation and Research and director of the FDA’s Oncology Center of Excellence, said in a press release. “Until now, the FDA has approved cancer treatments based on where in the body the cancer started — for example, lung or breast cancers. We have now approved a drug based on a tumor’s biomarker without regard to the tumor’s original location.”

The FDA based the accelerated approval in part on data from five uncontrolled, multicohort, multicenter, single-arm clinical trials designed to evaluate pembrolizumab in 149 patients — including 90 patients with colorectal cancer and 59 patients diagnosed with one of 14 other malignancies.

Patients received either 200 mg pembrolizumab every 3 weeks or 10 mg/kg pembrolizumab every 2 weeks for a maximum of 24 months or until unacceptable toxicity or disease progression.

Researchers reported an objective response rate of 39.6% (95% CI, 31.7-47.9) — including 11 complete responses and 48 partial responses — which appeared similar irrespective of malignancy (colorectal cancer, 36%; other cancer type, 46%). Seventy-eight percent of responding patients had responses that lasted for 6 months or longer.

The most common adverse reactions included fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation and nausea.

Immune-mediated side effects consisted of pneumonitis, colitis, hepatitis, endocrinopathies and nephritis.

In the prescribing information, a “limitation of use” label notes the safety and effectiveness of pembrolizumab in pediatric patients with microsatellite instability–high central nervous system cancers have not been established.

The FDA recommended a dose of 200 mg for adults or 2 mg/kg (up to a maximum of 200 mg) for children, administered as an IV infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.