FDA approves Keytruda (pembrolizumab) for advanced non-small cell lung cancer.

First drug approved in lung cancer for patients whose tumors express PD-L1.

October 2, 2015

The U.S. Food and Drug Administration granted accelerated approval for Keytruda (pembrolizumab) to treat patients with advanced (metastatic) non-small cell lung cancer (NSCLC) whose disease has progressed after other treatments and with tumors that express a protein called PD-L1. Keytruda is approved for use with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, the first test designed to detect PD-L1 expression in non-small cell lung tumors.


Pembrolizumab is a humanized monoclonal antibody that blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2. Pembrolizumab is an IgG4 kappa immunoglobulin with an approximate molecular weight of 149 kDa.


Mechanism of Action

Binding of the PD-1 ligands, PD-L1 and PD-L2, to the PD-1 receptor found on T cells, inhibits T cell proliferation and cytokine production. Upregulation of PD-1 ligands occurs in some tumors and signaling through this pathway can contribute to inhibition of active T-cell immune surveillance of tumors.



Pembrolizumab is a monoclonal antibody that binds to the PD-1 receptor and blocks its interaction with PD-L1 and PD-L2, releasing PD-1 pathway-mediated inhibition of the immune response, including the anti-tumor immune response. In syngeneic mouse tumor models, blocking PD-1 activity resulted in decreased tumor growth.

Safety & Efficacy

The safety of Keytruda was studied in 550 patients with advanced NSCLC.

The most common side effects of Keytruda included fatigue, decreased appetite, shortness of breath or impaired breathing (dyspnea) and cough.

Keytruda also has the potential to cause severe side effects that result from the immune system effect of Keytruda (known as “immune-mediated side effects”).

The effectiveness of Keytruda for this use was demonstrated in a subgroup of 61 patients enrolled within a larger multicenter, open-label, multi-part study.

The subgroup consisted of patients with advanced NSCLC that progressed following platinum-based chemotherapy or, if appropriate, targeted therapy for certain genetic mutations (ALK or EGFR).

This subgroup also had PD-L1 positive tumors based on the results of the 22C3 pharmDx diagnostic test.

Study participants received 10 mg/kg of Keytruda every two or three weeks. The major outcome measure was overall response rate (percentage of patients who experienced complete and partial shrinkage of their tumors).

Tumors shrank in 41 percent of patients treated with Keytruda and the effect lasted between 2.1 and 9.1 months.

In the 550 study participants with advanced NSCLC, severe immune-mediated side effects occurred involving the lungs, colon and hormone-producing glands.

Other uncommon immune-mediated side effects were rash and inflammation of blood vessels (vasculitis).

Women who are pregnant or breastfeeding should not take Keytruda because it may cause harm to a developing fetus or newborn baby.

Across clinical studies, a disorder in which the body’s immune system attacks part of the peripheral nervous system (Guillain-Barre Syndrome) also occurred.


 Administer 2 mg/kg as an intravenous infusion over 30 minutes every 3 weeks.

 Reconstitute and dilute prior to intravenous infusion.


For injection: 50 mg, lyophilized powder in single-use vial for reconstitution.


Immune-mediated adverse reactions: Administer corticosteroids based on the severity of the reaction.

Immune-mediated pneumonitis: Withhold for moderate, and permanently discontinue for severe or life-threatening pneumonitis.

Immune-mediated colitis: Withhold for moderate or severe, and permanently discontinue for life-threatening colitis.

Immune-mediated hepatitis: Monitor for changes in hepatic function. Based on severity of liver enzyme elevations, withhold or discontinue.

Immune-mediated hypophysitis: Withhold for moderate, withhold or discontinue for severe, and permanently discontinue for life-threatening hypophysitis.

 Immune-mediated nephritis: Monitor for changes in renal function. Withhold for moderate, and permanently discontinue for severe or life-threatening nephritis.

Immune-mediated hyperthyroidism and hypothyroidism: Monitor for changes in thyroid function. Withhold for severe and permanently discontinue for life-threatening hyperthyroidism.

Embryofetal Toxicity: KEYTRUDA may cause fetal harm. Advise females of reproductive potential of the potential risk to a fetus.


Most common adverse reactions (reported in ≥20% of patients) included fatigue, cough, nausea, pruritus, rash, decreased appetite, constipation, arthralgia, and diarrhea.

Keytruda was approved under the agency’s accelerated approval program, which allows the approval of a drug to treat a serious or life-threatening disease based on clinical data showing the drug has an effect on a surrogate endpoint reasonably likely to predict clinical benefit to patients. This program provides earlier patient access to promising new drugs while the company conducts confirmatory clinical trials. An improvement in survival or disease-related symptoms in patients being treated with Keytruda has not yet been established.

Keytruda is marketed by Merck & Co., based in Whitehouse Station, New Jersey and the PD-L1 IHC 22C3 pharmDx diagnostic test is marketed by Dako North America Inc. in Carpinteria, California.


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