EU approves Keytruda for microsatellite instability-high or deficient mismatch repair tumors
Merck Inc., announced that the European Commission has approved Keytruda (pembrolizumab) as monotherapy for the treatment of microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) tumors in adults with: unresectable or metastatic colorectal cancer after previous fluoropyrimidine-based combination therapy; advanced or recurrent endometrial carcinoma, who have disease progression on or following prior treatment with a platinum-containing therapy in any setting and who are not candidates for curative surgery or radiation; unresectable or metastatic gastric, small intestine or biliary cancer, who have disease progression on or following at least one prior therapy.
This is the second approval for Keytruda in Europe based on the MSI-H/dMMR biomarker. Keytruda is also approved for the first-line treatment of metastatic MSI-H or dMMR colorectal cancer in adults.
The approval was based on data from KEYNOTE-164 (NCT02460198) and KEYNOTE-158 (NCT02628067), multicenter, non-randomized, open-label Phase II trials evaluating Keytruda in patients with advanced MSI-H or dMMR solid tumors. The KEYNOTE-164 trial enrolled 124 patients with unresectable or metastatic MSI-H or dMMR colorectal cancer that progressed following prior fluoropyrimidine-based therapy in combination with irinotecan and/or oxaliplatin. The KEYNOTE-158 trial enrolled 355 patients with unresectable or metastatic MSI-H or dMMR solid tumors, including endometrial, gastric, small intestine or biliary cancer. Microsatellite instability or MMR tumor status was determined by prospectively using polymerase chain reaction or immunohistochemistry, respectively.
Patients received Keytruda 200 mg administered intravenously every three weeks until unacceptable toxicity or disease progression. Clinically stable patients with initial evidence of disease progression were permitted to remain on treatment until disease progression was confirmed. Patients without disease progression were treated for up to 24 months (up to 35 cycles). The primary efficacy outcome measure for the trials was objective response rate (ORR) as assessed by blinded independent central review using RECIST v1.1. The secondary efficacy outcome measures for the trials included duration of response (DOR), progression-free survival and overall survival.
The safety of KEYTRUDA as monotherapy has been evaluated in 7,148 patients with advanced melanoma, resected stage III melanoma (adjuvant therapy), non-small cell lung cancer, classical Hodgkin lymphoma, urothelial carcinoma, head and neck squamous cell carcinoma, colorectal cancer, endometrial, gastric, small intestine, biliary, pancreatic cancer or adjuvant therapy of renal cell carcinoma across four doses (2 mg/kg bodyweight [bw] every three weeks, 200 mg every three weeks or 10 mg/kg bw every two or three weeks) in clinical studies.
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