FDA grants pembrolizumab traditional approval for TMB-H solid tumors, ORR 36 percent
The FDA converted pembrolizumab's accelerated approval in TMB-H solid tumors to traditional approval on October 16, 2026, citing an objective response rate of 36 percent in 220 patients. The approval defines TMB-H as 13 mut/Mb or higher.
Machine-summarized from the primary sources listed below; not independently reported. How we use automation
On October 16, 2026, the FDA granted traditional approval to pembrolizumab (Keytruda, Merck) and to pembrolizumab and berahyaluronidase alfa-pmph (Keytruda Qlex, Merck) for adult and pediatric patients with unresectable or metastatic TMB-H solid tumors, the FDA said. Across 220 patients with tumors at 13 mut/Mb or higher, the objective response rate was 36 percent (95% CI: 30, 43). The approval converts an accelerated approval and sets the TMB-H cutoff at 13 mut/Mb.
| Tumor type | Responders | Objective response rate | 95% CI |
|---|---|---|---|
| Cervical cancer | 11 of 28 | 39% | 22%, 59% |
| Small cell lung cancer | 9 of 25 | 36% | 18%, 57% |
| Endometrial cancer | 10 of 19 | 53% | 29%, 76% |
| Breast cancer | 7 of 18 | 39% | 17%, 64% |
| Neuroendocrine cancer | 8 of 17 | 47% | 23%, 72% |
| Colorectal cancer | 1 of 10 | 10% | 0.3%, 45% |
| Skin squamous cell carcinoma | 6 of 8 | 75% | 35%, 97% |
From the Keytruda label on DailyMed (version published Nov 02, 2026), as cited in the FDA notice of October 16, 2026.
Why it matters
Previously, pembrolizumab held an accelerated approval in unresectable or metastatic TMB-H solid tumors defined as 10 mut/Mb or higher, the FDA said. The agency said this approval amends the indication to define TMB-H as 13 mut/Mb or higher, as efficacy to support traditional approval was not confirmed in patients with TMB of 10 to <13 mut/Mb. The Keytruda label, version published Nov 02, 2026, now lists the indication as section 1.18, for tumors as determined by an FDA-authorized test that have progressed following prior treatment and have no satisfactory alternative treatment options. The FDA Accelerated Approval Program page states that if the confirmatory trial shows clinical benefit, the FDA grants traditional approval.
Response and duration of response
The FDA page gives October 16, 2026 as the approval date and lists these results for the major efficacy outcome measures, objective response rate (ORR) and duration of response (DOR), assessed by BICR according to RECIST v1.1:
- 220 patients with tumors at 13 mut/Mb or higher received at least one dose: 145 in Cohort M and 75 in Cohorts A to J.
- ORR across both groups was 36% (95% CI: 30, 43).
- 58% of patients had a DOR of 12 months or longer.
The label adds that the complete response rate was 7% and the partial response rate was 29%. Duration of response was analyzed in 79 patients. Median duration of response was NR (not reached), with a range of 1.9+ to 112.8+ months, and 32% of responders had a duration of 24 months or longer. Median follow-up time was 17.3 months.
Response by tumor type
The label table lists the objective response rate by tumor type for tumors at 13 mut/Mb or higher.
- Cervical cancer: 11 of 28 patients responded (39%; 95% CI 22%, 59%).
- Small cell lung cancer: 9 of 25 (36%; 95% CI 18%, 57%).
- Endometrial cancer: 10 of 19 (53%; 95% CI 29%, 76%).
- Breast cancer: 7 of 18 (39%; 95% CI 17%, 64%).
- Neuroendocrine cancer: 8 of 17 (47%; 95% CI 23%, 72%).
- Colorectal cancer: 1 of 10 (10%; 95% CI 0.3%, 45%).
- Skin squamous cell carcinoma: 6 of 8 (75%; 95% CI 35%, 97%).
Trial design and patients
Efficacy was evaluated in two groups of patients in KEYNOTE-158 (NCT02628067). Cohort M prospectively enrolled patients with tumors that were TMB-H and not microsatellite instability-high (MSI-H). Cohorts A through J were a prospectively planned retrospective analysis of patients with TMB-H tumors identified within 10 cohorts of patients with various previously treated unresectable or metastatic solid tumors.
Patients in Cohorts A to J received pembrolizumab 200 mg every three weeks. Patients in Cohort M received 400 mg intravenously every six weeks. Treatment continued until unacceptable toxicity or documented disease progression. The label says the trial excluded patients who previously received an anti-PD-1 or other immune-modulating monoclonal antibody, or who had an autoimmune disease or a medical condition that required immunosuppression. Tumor mutational burden was identified using the FoundationOne assay.
The label describes the 220 patients with TMB-H tumors:
- median age of 63 years (range: 27 to 89), with 44% age 65 or older
- 39% male and 62% White
- 41% with ECOG PS of 0 and 59% with ECOG PS of 1
- 59% had at least two prior lines of therapy
Dosage and safety
The recommended dose of pembrolizumab monotherapy for the updated indication is 200 mg every three weeks or 400 mg every six weeks until disease progression, unacceptable toxicity, or up to 24 months. For pediatric patients the dose is 2 mg/kg every three weeks (up to a maximum of 200 mg) on the same stopping terms. The FDA said the safety profile for the updated indication was consistent with the known safety profile of pembrolizumab monotherapy.
The prescribing information includes warnings and precautions for immune-mediated adverse reactions, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.
What remains uncertain
- Efficacy to support traditional approval was not confirmed in patients with TMB of 10 to <13 mut/Mb, the FDA said.
- Full prescribing information for Keytruda and Keytruda Qlex is to be posted on Drugs@FDA, the FDA said.