FDA Grants Full Approval to Merck’s Keytruda for MSI-H/dMMR Solid Tumors

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The FDA has granted full approval to pembrolizumab (Keytruda; Merck) for the treatment of adults and children with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, determined by an FDA-approved test, that have progressed following prior treatment and have no satisfactory alternative treatment options.

This is the first full approval for an immunotherapy based on a predictive biomarker, regardless of solid tumor type.

“This approval reinforces the important role of Keytruda 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 a statement. “These data also further underscore the need for biomarker testing to identify patients who may be eligible for this therapy.”

The full approval was based on results from the phase 2 KEYNOTE-158 (NCT02628067), KEYNOTE-164 (NCT02460198), and KEYNOTE-051 (NCT02332668) trials, which included data on 504 adult and children across more than 30 types of cancer.

KEYNOTE-164 enrolled 124 individuals with advanced MSI-H/dMMR colorectal cancer that progressed following treatment with fluoropyrimidine and either irinotecan or oxaliplatin with or without anti-VEGF/EGFR mAb-based therapy. KEYNOTE-158 enrolled 373 individuals with advanced MSI-H/dMMR non-colorectal cancers who had disease progression following prior therapy.

Additionally, KEYNOTE-051 enrolled 7 children with MSI-H/dMMR cancers.

In the pooled analysis of the 3 trials, pembrolizumab demonstrated an overall response rate (ORR) of 33.3%, including a complete response rate of 10.3% and partial response rate of 23%. There was a median follow-up time of 20.1 months.

Of the responding patients, 77% had responses lasting 12 months or longer and 39% lasting 36 months or longer. The median duration of response (DOR) was 63.2 months.

For individuals with MSI-H/dMMR colorectal cancer, the ORR was 34% with a DOR ranging from 4.4 to 58.5 months or more.

“Today’s approval builds on the 2017 accelerated approval of Keytruda as the first immunotherapy with a tumor agnostic indication and supports the role of Keytruda as an effective immunotherapy option based on a pan-tumor predictive biomarker,” Scot Ebbinghaus, MD, vice president of global clinical development at Merck Research Laboratories, said in the statement. “This milestone reflects Merck’s longstanding commitment to biomarker research and personalizing treatment strategies for patients.”

For other MSI-H/dMMR non-colorectal solid tumors, the ORR was 33%, with a DOR ranging from 1.9 to 63.9 months or more.

For the KEYNOTE-158 and KEYNOTE-164 studies, the median duration of exposure to pembrolizumab was 6.2 months, while the median duration of exposure was 2.1 months for the KEYNOTE-051 study.

Adults received pembrolizumab in the 200-mg dosage, administered intravenously every 3 weeks, while children received 2 mg/kg every 3 weeks.

In the KEYNOTE-158 and KEYNOTE-164 studies, the assessment of tumor status was performed every 9 weeks through the first year and then every 12 weeks after.

In KEYNOTE-051, the assessment of tumor status was performed every 8 weeks for 24 weeks and then every 12 weeks after.

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. Merck. News release. March 29, 2023. Accessed March 30, 2023. https://www.merck.com/news/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/