US FDA traditional approval — 2026-10-16 (converted from accelerated approval) Approved in Japan — February 2022 (TMB ≥10 cutoff) Evidence: phase 2 KEYNOTE-158, 220 patients
On October 16, 2026, the US FDA granted traditional (full) approval to the immunotherapy Keytruda (pembrolizumab) for TMB-high solid tumors. Among 220 patients whose tumors carried a high tumor mutational burden (TMB), 36% saw their tumors shrink, and 58% of those responders kept their response for more than a year. With this approval, the eligibility cutoff was set at 13 mutations per megabase instead of 10.
TMB-high tumors carry many mutations, and the approval is now full
Tumor mutational burden (TMB) is a number that shows how many mutations a cancer cell's genes carry, measured in mutations per megabase (mut/Mb). Cancer cells with many mutations make many abnormal protein fragments, which makes them easier for immune cells to recognize. That is why PD-1 inhibitors, which release the brakes on the immune system, tend to work well in these cancers.
Keytruda received accelerated approval in the US in June 2020 for solid tumors with TMB of 10 or more. Accelerated approval allows a drug onto the market based on early data, with benefit to be confirmed later. Now that the confirmatory data have been reviewed, the indication has become a traditional approval. Because efficacy sufficient for full approval was not confirmed in patients with TMB of 10 to under 13, the cutoff was raised to 13 or more. In effect, the label now points more precisely to the patients who benefit most.
This is a "tumor-agnostic" approval: eligibility depends on a genetic feature rather than the organ where the cancer started. Similar approvals exist for immunotherapy in MSI-H or dMMR cancers; see our article on dostarlimab for rectal cancer.
Who is eligible: TMB of 13 or more after prior treatment
Under the FDA label, patients must meet all of the following:
- Adults or children with a solid tumor that cannot be removed by surgery or has spread
- TMB of 13 mut/Mb or more on an FDA-authorized test
- Disease that progressed after prior treatment, with no satisfactory alternative treatment options
The supporting KEYNOTE-158 trial included patients with anal, biliary, cervical, endometrial, neuroendocrine, salivary gland, small-cell lung, thyroid and vulvar cancers, as well as mesothelioma. Cohort M enrolled only patients whose tumors were TMB-high and not MSI-high from the start. This means a tumor can qualify through a high TMB even when it is not MSI-high.
TMB is measured with a gene panel test on tumor tissue. A widely used example is FoundationOne CDx, which reads more than 300 genes at once. If you have already had a panel test, check whether the report lists a TMB value.
Results: 36% of 220 patients responded, and 58% of responders lasted over a year
The full approval is based on 220 patients in KEYNOTE-158 with TMB of 13 or more: 145 from Cohort M, enrolled as TMB-high from the outset, and 75 from Cohorts A–J identified in a pre-planned analysis. Tumor response was judged on scans by a blinded independent central review.
| Measure | Result |
|---|---|
| Patients evaluated | 220 (Cohort M 145, Cohorts A–J 75) |
| Objective response rate | 36% (95% CI 30–43%) |
| Response lasting 12 months or more | 58% of responders |
| Eligibility cutoff | TMB ≥13 mut/Mb (previously ≥10 under accelerated approval) |
| Dosing | Adults 200 mg every 3 weeks or 400 mg every 6 weeks, up to 24 months |
Sources: US FDA approval notice (2026-10-16), The ASCO Post (2026-10-22). The objective response rate is the share of patients whose tumors shrank by a set amount on scans.
A KEYNOTE-158 analysis published in Lancet Oncology in 2020 also found a response rate of 29% in patients with high TMB, compared with 6% in those with lower TMB. The 3-year survival rate was 32% in the high-TMB group versus 22% in the lower-TMB group. These are meaningful results in a trial where many patients had already received several lines of treatment.
Dr. Chinmay Jani of Sylvester Comprehensive Cancer Center said the decision adds evidence that TMB is a useful marker of immunotherapy benefit across many tumor types.
Side effects and management: spotting immune-related effects early
The FDA stated that safety in these patients was consistent with the known profile of Keytruda alone. Because Keytruda activates the immune system, immune cells can sometimes attack healthy organs, causing immune-related side effects. Common examples are thyroid changes, pneumonitis (interstitial lung disease), diarrhea or colitis, raised liver enzymes and skin rash.
Most of these can be managed with steroids or hormone replacement when found early. Contact your care team right away, rather than waiting for the next visit, if you develop shortness of breath or a lasting cough, diarrhea several times a day, severe fatigue or skin changes. The label also lists infusion reactions, complications after stem cell transplant and harm to an unborn baby as precautions.
Where it is available: full approval in the US, approved in Japan since 2022
- United States: traditional approval on October 16, 2026, covering both intravenous Keytruda and subcutaneous Keytruda Qlex.
- Japan: approved in February 2022 for advanced or recurrent TMB-high solid tumors that progressed after chemotherapy, when standard treatment is difficult. Japan's cutoff at approval was TMB 10 or more, and FoundationOne CDx was approved in November 2021 as the test to select patients. Whether the new US cutoff will be reflected in Japan can be checked in announcements from Japan's Pharmaceuticals and Medical Devices Agency (PMDA).
- Gene panel testing in Japan: since June 2019, patients with solid tumors who have finished, or are about to finish, standard treatment can receive gene panel testing under public health insurance (National Cancer Center Japan).
For general information on care in Japan, see Other medical information; for treatments that use immune cells, see Types of immune cell therapy compared.
What to check and questions for your doctor
- Does my gene panel report include a TMB value? Is it 13 or more?
- If I have not been tested, which test can measure my TMB?
- Is my cancer also MSI-high or dMMR?
- Besides Keytruda, what other treatments could I consider at this stage?
- Which symptoms of immune-related side effects should I report first?
Frequently asked questions
What does TMB-high mean?
It means the cancer cells carry many gene mutations. Under the new US approval, TMB-high means 13 mut/Mb or more. Cancers with many mutations are easier for immune cells to recognize, so immunotherapy tends to work better.
How well does Keytruda work in TMB-high solid tumors?
Among 220 patients with TMB of 13 or more, 36% had tumor shrinkage, and 58% of responders kept their response for at least a year. These patients had already progressed after earlier treatment.
Why was the TMB cutoff changed from 10 to 13?
After reviewing further data, efficacy sufficient for full approval was not confirmed in patients with TMB of 10 to under 13. The cutoff was therefore set at 13 or more, where the benefit is clear.
Can I receive Keytruda for TMB-high cancer in Japan?
Yes. Japan approved it in February 2022 for TMB-high solid tumors that progressed after chemotherapy. Eligibility depends on gene panel results and your doctor's assessment.
Related: FDA approves atezolizumab for dMMR colon cancer · New head and neck cancer drug petosemtamab · All articles by cancer type
Sources
- U.S. FDA — FDA grants traditional approval to pembrolizumab or pembrolizumab and berahyaluronidase alfa-pmph for TMB-H solid tumors (2026-10-16)
fda.gov
Checked: 2026-11-01 - The ASCO Post — FDA grants traditional approval to pembrolizumab for TMB-H solid tumors (2026-10)
ascopost.com
Checked: 2026-11-01 - CancerNetwork — FDA approves pembrolizumab in metastatic TMB-H solid tumors (2026-10-22)
cancernetwork.com
Checked: 2026-11-01 - ESMO OncologyPRO — High TMB proposed as pembrolizumab biomarker for advanced solid cancers (KEYNOTE-158, Lancet Oncology 2020)
oncologypro.esmo.org
Checked: 2026-11-01 - PMDA — Keytruda review report, 2022 (TMB-High solid tumor indication approved February 2022) (Japanese-language document)
pmda.go.jp
Checked: 2026-11-01 - Chugai — FoundationOne CDx approved in Japan to identify TMB-High solid tumors (2021-11-16)
1stoncology.com
Checked: 2026-11-01 - National Cancer Center Japan — OncoGuide NCC Oncopanel System covered by National Health Insurance (2020-04-01)
ncc.go.jp
Checked: 2026-11-01 - ClinicalTrials.gov — NCT02628067: KEYNOTE-158
clinicaltrials.gov/study/NCT02628067
Checked: 2026-11-01
Written by the FTH editorial team. Sources checked 2026-11-01 · Medical review: not applicable
This article is general information based on public sources and does not replace diagnosis or treatment. Please discuss treatment decisions with your medical team.
