The US Food and Drug Administration (FDA) has granted accelerated approval for the agency’s first tissue/site agnostic indication to pembrolizumab.1

The agent is now approved for adults and children with unresectable or metastatic, microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) solid tumors that have progressed and for whom there are no alternative treatment options.

This approval is also for those with MSI-I or dMMR colorectal cancer that has progressed after treatment with a fluoropyrimidine, oxaliplatin, and irinotecan.

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The accelerated approved was based on tumor response rate and durability of response, with continued approval contingent on confirmatory clinical trials.2

Results from 149 patients with MSI-H or dMMR cancers enrolled in 5 uncontrolled single-arm clinical trials — 90 with colorectal cancer and 59 with 1 of 14 other cancer types — who received pembrolizumab 200 mg every 3 weeks or 10 mg/kg every 2 weeks for up to 24 months supported the approval.

Objective response rate (ORR), assessed according to RECIST 1.1 by blinded independent central radiologist review, and response duration were the major efficacy outcomes.

The ORR was 39.6% (95% CI, 31.7-47.9), with responses lasting 6 months or more for 78% of patients who responded to pembrolizumab. The ORR was similar among patients diagnosed with colorectal cancer, 36%, or 1 of the 14 other cancer types, 46%. Eleven patients had a complete response and 48 had a partial response.

Of the 149 patients, 135 had tumor status prospectively determined using PCR tests for MSI-H or IHC tests for dMMR. For the other 14 patients, MSH-I status was determined retrospectively.

The most common adverse reactions, reported in 20% or more of patients, were fatigue, pruritus, diarrhea, decreased appetite, rash, pyrexia, cough, dyspnea, musculoskeletal pain, constipation, and nausea.

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The recommended pembrolizumab dose is 200 mg for adults or 2 mg/kg (up to a maximum of 200 mg) for children, administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

The indication includes a “limitation of use”: the safety and effectiveness of pembrolizumab in pediatric patients with MSI-H central nervous system cancers has not been established.


  1. FDA grants accelerated approval to pembrolizumab for first tissue/site agnostic indication [news release]. Silver Spring, MD: US Food and Drug Administration; May 23, 2017. Accessed May 23, 2017.
  2. KEYTRUDA Prescribing information. Whitehouse Station, NJ: Merck & Co, Inc.; May 2017. Accessed May 23, 2017.