FDA Approves Keytruda to Treat Tumor Mutational Burden-High Solid Tumors

June 17, 2020

The Food and Drug Administration approved the second biomarker-based indication for Keytruda to treat adult and pediatric patients with unresectable or metastatic TMB-H solid tumors across cancer types, including rare cancers.

The Food and Drug Administration (FDA) approved Keytruda (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic tumor mutational burden-high (TMB-H) solid tumors, according to Merck — the agent’s manufacturer.

Moreover, the agency approved FoundationOne® CDx test as the companion diagnostic to identify patients with solid tumors that are TMB-H who may benefit from treatment with Keytruda alone.

Of note, the anti-PD-1 therapy is approved for those who have progressed following prior treatment and who have no satisfactory alternative treatment options.

“As physicians, we are always looking to find new options for patients, especially in the second-line or higher treatment setting,” Dr. Roy S. Herbst, 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 a press 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 TMB-H tumors across cancer types, including rare cancers.”

The FDA granted accelerated approval to Keytruda for this indication based on tumor response rate and durability of response from a prospectively-planned retrospective analysis of 10 cohorts of patients with various previously treated unresectable or metastatic solid tumors with TMB-H that were enrolled in the multicenter, non-randomized, open-label KEYNOTE-158 trial.

Major efficacy outcome measures included overall response rate and duration of response in patients treated with 200 mg of Keytruda every three weeks.

Of 102 patients treated, 29% experienced a response to treatment (30 patients) — including 4% with a complete response and 25% with a partial response. In addition, 57% of patients who experienced a response to treatment had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer.

After a median follow-up of 11.1 months, the median duration of response had not been reached.

In a pre-specified analysis of 70 patients with TMB of 13 or more, 37% of patients demonstrated a response to treatment with Keytruda (26 patients), including 3% with a complete response and 34% with a partial response. In addition, 58% had ongoing responses of 12 months or longer, and 50% had ongoing responses of 24 months or longer.

The median duration of response in this subgroup was also not reached.

The most common side effects were fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, constipation, pain and abdominal pain.

Because this is granted under accelerated approval by the FDA, continued approval for this indication of Keytruda may be contingent upon verification and description of clinical benefit in confirmatory trials.


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