Keytruda Granted Full Approval for Advanced MSI-H or dMMR Solid Tumors

Keytruda is a programmed death receptor-1 (PD-1)-blocking antibody.

The Food and Drug Administration (FDA) has granted full approval to Keytruda® (pembrolizumab) for the treatment of adult and pediatric patients with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors, as determined by an FDA-approved test, that have progressed following prior treatment and who have no satisfactory alternative treatment options. 

Keytruda was previously granted accelerated approval for this indication. The conversion to regular approval was based on data from the phase 2 KEYNOTE-158 trial ( Identifier: NCT02628067), the KEYNOTE-164 trial ( Identifier: NCT02628067), and the KEYNOTE-051 trial ( Identifier: NCT02628067), which included 504 patients with over 30 types of cancer.

KEYNOTE-158 enrolled 373 patients with advanced MSI-H/dMMR non-colorectal cancers who had disease progression following prior therapy. KEYNOTE-164 included 124 patients with advanced MSI-H/dMMR colorectal cancer that progressed following treatment with fluoropyrimidine and either oxaliplatin or irinotecan with or without anti-VEGF/EGFR mAb-based therapy. KEYNOTE-051 included 7 pediatric patients with MSI-H/dMMR cancers.

Adult patients received pembrolizumab 200mg intravenously every 3 weeks (pediatric patients received 2mg/kg every 3 weeks) until acceptable toxicity, disease progression or a maximum of 24 months. The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR).

In a pooled analysis of the trials, the ORR was 33.3% (95% CI, 29.2-37.6) at a median follow-up time of 20.1 months (range, 0.1 to 71.4 months); 10.3% of patients had a complete response and 23.0% of patients had a partial response. Among the 168 responders, 77% had responses lasting at 12 months or longer and 39% had responses lasting 36 months or longer. The median DOR was 63.2 months (range, 1.9+ to 63.9+ months).

Among patients with MSI-H/dMMR colorectal cancer (n=124), the ORR was 34% (95% CI, 26-43) with a DOR ranging from 4.4 to 58.5+ months. Among those with other MSI-H/dMMR non-colorectal solid tumors (n=380), the ORR was 33% (95% CI, 28-38) with a DOR ranging from 1.9+ to 63.9+ months.

Non-colorectal solid tumors included endometrial cancer, gastric or gastroesophageal junction cancer, small intestinal cancer, brain cancer, ovarian cancer, biliary cancer, pancreatic cancer, sarcoma, breast cancer, cervical cancer, neuroendocrine cancer, prostate cancer, adrenocortical cancer, mesothelioma, thyroid cancer, small cell lung cancer, bladder cancer, salivary cancer, renal cell cancer and other cancers.

“This approval reinforces the important role of Keytruda in certain patients with MSI-H or dMMR solid tumors facing a variety of cancers,” said Dr Luis A. Diaz, Jr, head of the Division of Solid Tumor Oncology, Memorial Sloan Kettering Cancer Center. “These data also further underscore the need for biomarker testing to identify patients who may be eligible for this therapy.”


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. Accessed March 30, 2023.