The FDA has 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.

Keytruda works by targeting the cellular pathway known as PD-1/PD-L1 (proteins found on the body’s immune cells and some cancer cells). By blocking the pathway, Keytruda may help the body’s immune system fight the cancer cells. In 2014, Keytruda was approved to treat patients with advanced melanoma following treatment with ipilimumab, a type of immunotherapy. Another drug, Opdivo (nivolumab), manufactured by Bristol-Myers Squibb, also targets the PD-1/PD-L1 pathway and was approved to treat squamous non-small cell lung cancer (a certain kind of NSCLC) in 2015.

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

Study participants received 10mg/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% of patients treated with Keytruda and the effect lasted between 2.1 and 9.1 months.

The FDA granted Keytruda Breakthrough Therapy designation for the indication because Merck demonstrated through preliminary clinical evidence that the drug may offer a substantial improvement over available therapies. The drug also received Priority Review status, which is granted to drugs that, at the time the application was submitted, have the potential to be a significant improvement in safety or effectiveness in the treatment of a serious condition.