FDA approves Keytruda for tumor mutational burden-high solid tumors
The FDA approved a second biomarker-based indication for the anti-PD-1 therapy pembrolizumab.
The accelerated approval applies to use of pembrolizumab (Keytruda, Merck) for adults or children with unresectable or metastatic tumor mutational burden-high solid tumors that progressed after prior treatment, and for whom no satisfactory alternative treatment options exist.
Tumor mutational burden-high status — which must be determined by an FDA-approved test — is defined as 10 or more mutations per megabase.
“For the second time, Keytruda monotherapy is now approved based on a biomarker rather than the location in the body where the tumor originated,” Scot W. Ebbinghaus, MD, vice president for clinical research at Merck Research Laboratories, said in a company-issued press release. “We’re pleased that our collaborative efforts to advance biomarker research have resulted in our ability to provide a new treatment option that addresses a high unmet medical need for these patients with cancer.”
The FDA also approved FoundationOne CDx (Foundation Medicine) as a companion diagnostic to identify patients with solid tumors that are tumor mutational burden-high who may benefit from pembrolizumab monotherapy.
The agency based the approvals on results of a prospectively planned retrospective analysis of the nonrandomized, open-label KEYNOTE-158 trial.
The analysis included 102 patients (median age, 61 years; range, 27-80; 34% male; 81% white) with previously treated unresectable or metastatic tumor mutational burden-high solid tumors as determined by the FoundationOne CDx assay.
No patients had received prior anti-PD-1 or immune-modulating monoclonal antibody therapy. Patients had ECOG performance status of 0 (41%) or 1 (58%), and 56% had received at least two prior lines of therapy.
All patients received pembrolizumab dosed at 200 mg every 3 weeks. They underwent tumor response assessment every 9 weeks for the first 12 months, and every 12 weeks thereafter.
Objective response rate and duration of response as assessed by blinded independent central review served as primary efficacy outcomes.
Researchers reported an ORR of 29% (95% CI, 21-39), including a 4% complete response rate and 25% partial response rate.
After median follow-up of 11.1 months, median duration of response had not been reached (range, 2.2+ months to 34.8%+ months).
Fifty-seven percent of patients who responded to therapy had ongoing responses of 12 months or longer, and 50% had ongoing responses for 24 months or longer.
The most common adverse events reported among pembrolizumab-treated patients included fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain and abdominal pain.
“As physicians, we are always looking to find new options for patients, especially in the second-line or higher treatment setting,” Roy S. Herbst, MD, PhD, Ensign professor of medicine (medical oncology) and professor of pharmacology at Yale School of Medicine, chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital, and associate cancer center director for translational research at Yale Cancer Center, said in the release. “It’s great to see the use of innovative biomarkers and immunotherapy come together with this approval and encouraging that we now have an option for patients with tumor mutational burden-high tumors across cancer types, including rare cancers.”
The FDA previously approved pembrolizumab for treatment of adults and children with previously treated microsatellite instability-high metastatic tumors regardless of tumor type or site.