FDA Grants Traditional Approval to Keytruda for TMB-H Solid Tumors

The U.S. Food and Drug Administration (FDA) has granted traditional approval to Keytruda (pembrolizumab) or Keytruda Qlex (pembrolizumab and berahyaluronidase alfa-pmph) for adults and children with certain unresectable or metastatic solid tumors that have high tumor mutational burden (TMB-H) and have progressed after prior treatment.

The approval, announced Oct. 16, 2026, applies to tumors with at least 13 mutations per megabase (mut/Mb), as determined by an FDA-authorized test. Patients must also have no satisfactory alternative treatment options.

This decision converts Keytruda’s previous accelerated approval for this indication to traditional approval and updates the threshold used to identify eligible patients.

Who May Be Eligible for Keytruda?

Tumor mutational burden measures the number of mutations in a tumor’s DNA. A high tumor mutational burden may help identify cancers that could respond to certain immunotherapies, including Keytruda.

Previously, Keytruda received accelerated approval for adults and children with unresectable or metastatic solid tumors with a TMB of at least 10 mutations per megabase. Under the updated approval, the threshold is now at least 13 mutations per megabase.

The change follows confirmatory data that did not establish sufficient efficacy for patients whose tumors had a TMB between 10 and fewer than 13 mutations per megabase.

The treatment is intended for patients whose cancer has progressed following prior treatment and who do not have satisfactory alternative treatment options. An FDA-authorized test is needed to determine whether a tumor meets the TMB-H threshold.

What Did the Clinical Trial Find?

The FDA evaluated data from the KEYNOTE-158 clinical trial (NCT02628067), which included patients with previously treated, unresectable or metastatic solid tumors.

The analysis included 220 patients whose tumors had a TMB of at least 13 mutations per megabase. Of these patients, 145 were enrolled in Cohort M, which prospectively included patients with TMB-H tumors that were not microsatellite instability-high (MSI-H). The other 75 patients were identified through a planned retrospective analysis of patients enrolled in Cohorts A through J.

Researchers assessed the objective response rate (ORR), or the percentage of patients whose cancer shrank or disappeared following treatment, and duration of response (DOR), which measures how long that response lasted.

Across both groups, the objective response rate was 36%. Among patients who responded to treatment, 58% maintained their response for at least 12 months.

These findings supported the FDA’s decision to grant traditional approval for patients whose tumors meet the updated TMB-H threshold.

What This Approval Means for Patients

This approval provides an established treatment option for eligible patients with certain advanced solid tumors whose cancer has progressed after previous treatment and who have no satisfactory alternative treatment options.

However, the updated approval also changes which patients may qualify for Keytruda under this indication. Previously, tumors with at least 10 mutations per megabase could meet the definition of TMB-H. The threshold is now at least 13 mutations per megabase, meaning some patients who met the previous criteria may no longer qualify.

Patients can ask their health care team whether tumor mutational burden testing has been performed on their cancer and whether their results meet the updated criteria. Eligibility also depends on having unresectable or metastatic disease, progression after prior treatment and no satisfactory alternative treatment options.

Although the clinical trial showed that some patients experienced tumor shrinkage and long-lasting responses, Keytruda does not work for everyone. Patients should discuss the potential benefits, risks and other available treatment options with their oncologist.

What Should Patients Know About Keytruda’s Safety?

The safety profile of Keytruda when used alone for this indication was consistent with its established safety profile.

However, treatment can cause serious side effects. The FDA prescribing information includes warnings for immune-mediated adverse reactions, infusion-related reactions, complications associated with allogeneic hematopoietic stem cell transplantation and embryo-fetal toxicity.

Immune-mediated reactions occur when the immune system attacks healthy tissues and may affect different parts of the body. Patients should discuss potential side effects and individual risk factors with their health care team and report new or worsening symptoms during treatment.

How Is Keytruda Given?

For adults receiving Keytruda alone for this indication, the recommended dose is 200 milligrams every three weeks or 400 milligrams every six weeks. Treatment may continue until the cancer progresses, side effects become unacceptable or the patient reaches 24 months of treatment.

For children, the recommended dose is 2 milligrams per kilogram of body weight every three weeks, up to a maximum of 200 milligrams. Treatment may continue until disease progression, unacceptable toxicity or a maximum of 24 months.

For information about dosing and administration of Keytruda Qlex, patients and health care professionals should consult its prescribing information.