FDA Gives Full Approval to Pembrolizumab in dMMR/MSI-H Solid Tumors

The FDA has granted full approval to pembrolizumab (Keytruda) for adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options, according to a press release from Merck.

"This approval reinforces the important role of [pembrolizumab] in certain patients with MSI-H or dMMR solid tumors facing a variety of cancers," according to an expert from Memorial Sloan Kettering Cancer Center.

Use of an FDA-approved test can determine if patients are eligible for treatment. The approval is based on results from the phase 2 KEYNOTE-158 (NCT02628067), KEYNOTE-164 (NCT02460198), and KEYNOTE-051 trials (NCT02332668). These trials collectively analyzed 504 patients across more than 30 different types of cancer.

“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, head of the Division of Solid Tumor Oncology at Memorial Sloan Kettering Cancer Center, said in the press release. “These data also further underscore the need for biomarker testing to identify patients who may be eligible for this therapy.”

In the trials, adults patients received 200 mg of pembrolizumab intravenously every 3 weeks, and pediatric patients received 2 mg/kg of the agent every 3 weeks until unacceptable toxicity, disease progression, or up to 24 months of treatment.

In a pooled analysis done with all 3 trials, the objective response rate (ORR) was 33.3% (95% CI, 29.2%-37.6%), including a complete response rate of 10.3%, and a partial response rate of 23.0%. The median follow-up was 20.1 months.

In 168 patients who were responders, 77% of patients had a lasting response of 12 months or more, with 39% having responses that lasted 36 months or more. The median duration of response was 63.2 months.

Of note, in patients with MSI-H/dMMR colorectal cancer (CRC; n = 124), the ORR was 34% (95% CI, 26%-43%), and the duration of response (DOR) ranged from 4.4 months to 58.5+ months. For patients who did not have CRC (n = 380), the ORR was 33% (95% CI, 28%-38%), and the DOR was 1.9 months to 63.9+ months.

The median duration of exposure in the KEYNOTE-158 and KEYNOTE-164 trials was 6.2 months. In the KEYNOTE-051 trial, the median duration of exposure was 2.1 months.

Reference

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. https://bit.ly/40rC1N4