Pembrolizumab Receives Full FDA Approval for Treatment of Select Patients With dMMR/MSI-H Solid Tumors


The FDA has granted full approval to pembrolizumab (Keytruda) for certain adult and pediatric patients with advanced MSI-H or dMMR solid tumors.

The FDA has granted full regular approval to pembrolizumab (Keytruda) for the treatment of adult and pediatric patients with unresectable mismatch repair deficient (dMMR) or microsatellite instability-high tumors (MSI-H) tumors who have disease progression on prior treatment and for whom other satisfactory treatment options do not exist. dMMR and MSI-H status must be confirmed by an FDA-approved test according to the indication.1

The approval is based on data from KEYNOTE-158 (NCT02628067), which evaluated the agent in advanced solid tumors, KEYNOTE-164 (NCT02460198), which evaluated the agent in patients with previously treated, locally advanced unresectable or metastatic colorectal cancer (CRC), and KEYNOTE-051 (NCT02332668), which evaluated pediatric patients with advanced solid tumors or lymphoma.1

In May 2017, the FDA granted accelerated approval to the PD-1 inhibitor for the same indication, marking the first tumor agnostic approval from the agency. At the same time, the agent was also approved for patients with dMMR/MSI-H CRC that had progressed following treatment with fluoropyrimidine, oxaliplatin, and irinotecan.2

In a pooled analysis of 504 patients from the 3 trials, at a median follow-up of 20.1 months (range, 0.1-71.4), the objective response rate (ORR) was 33.3% (95% CI, 29.2%-37.6%). This included a complete response rate of 10.3% and a partial response rate of 23.0%. Among responders the median duration of response (DOR) was 63.2 months with 77% of responders having a response lasting at least 12 months and 39% having a response that lasted at least 36 months.1

Among 124 patients with dMMR/MSI-H CRC, the ORR was 34% (95% CI, 26%-43%). The duration of response ranged from 4.4 months to ongoing responses observed at 58.5 months.1 In 2020, pembrolizumab was approved for the frontline treatment of this patient population based on data from the KEYNOTE-177 trial (NCT02563002).3

The expanded indication adds to the FDA approval of pembrolizumab for the treatment of patients with dMMR/MSI-H advanced endometrial cancer based on data from KEYNOTE-158, granted in March of 2022.4

Supporting the approval of all other tumor types beyond CRC, the collective ORR was 33% (95% CI, 28%-38%) with a DOR ranging from 1.9 months to ongoing at 63.9 months. In terms of exposure to the therapy, the median duration of exposure was 6.2 months (range, 1 day to 53.5 months) in KEYNOTE-158 and KEYNOTE-164 and was 2.1 months (range, 1 day to 25 months) in KEYNOTE-051.1

The administration of pembrolizumab for adult patients was 200 mg intravenously every 3 weeks until unacceptable toxicity, disease progression, or a maximum of 2 years. For pediatric patients the dose was 2 mg/kg every 3 weeks. Of note, the trials excluded patients with autoimmune disease or a medical condition that required immunosuppression.1

Select safety warnings include severe and fatal immune-mediated adverse reactions including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, nephritis with renal dysfunction, dermatologic adverse reactions, and cardiac events.1

“This approval reinforces the important role of [pembrolizumab] in certain patients with MSI-H or dMMR solid tumors facing a variety of cancers,” Luis A. Diaz, Jr, MD, said in a news release.1 “These data also further underscore the need for biomarker testing to identify patients who may be eligible for this therapy.” Diaz is the head of the Division of Solid Tumor Oncology, and the Grayer Family Chair at Memorial Sloan Kettering Cancer Center in New York, New York.


  1. FDA converts to full approval indication for Keytruda (pembrolizumab) for certain adult and pediatric patients with advanced microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors. News release. Merck. March 29, 2023. Accessed March 29, 2023.
  2. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication. FDA. Updated May 30, 2017. Accessed March 29 2023.
  3. FDA approves pembrolizumab for first-line treatment of MSI-H/dMMR colorectal cancer. FDA. Updated June 30, 2020. Accessed March 29, 2023.
  4. FDA approves pembrolizumab for advanced endometrial carcinoma. FDA. March 21, 2022. Accessed March 29, 2023.
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