The European Commission (EC) has approved Keytruda (pembrolizumab), Merck's anti-PD-1 therapy, at a dose of 2 mg/kg every three weeks, for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) in patients whose tumors express PD-L1 and who have received at least one prior chemotherapy regimen. Patients with EGFR or ALK positive tumor mutations should also have received approved therapy for these mutations prior to receiving Keytruda. The EC approval allows marketing of Keytruda in all 28 EU member states.

The approval is based on findings from KEYNOTE-010, a pivotal study which showed Keytruda significantly improved overall survival (OS) compared to standard of care chemotherapy.

“This approval provides an important new treatment regimen for patients in Europe with advanced lung cancer, one of the most common and challenging cancers,” said Dr. Roger Dansey, senior vice president and therapeutic area head, oncology late-stage development, Merck Research Laboratories. “In the KEYNOTE-010 trial, patients with advanced lung cancer who had failed prior regimens experienced improved overall survival when treated with Keytruda as compared with those treated with traditional chemotherapy.”

“The survival benefit for Keytruda observed in previously-treated patients who express PD-L1 is promising,” said Dr. Luis Paz-Ares, chair of the medical oncology department, Hospital Universitario, Madrid, Spain. “There is a significant unmet need for lung cancer patients, and with this approval, we now have a new personalized treatment option which uses biomarker testing to predict which patients are most likely to benefit from treatment.”

KEYNOTE-010 is a global, open-label, randomized, pivotal phase 2/3 study evaluating Keytruda (pembrolizumab) (2 mg/kg or 10 mg/kg every three weeks) compared to standard of care chemotherapy (docetaxel, 75 mg/m2 every three weeks) in 1,033 patients with squamous and non-squamous NSCLC who experienced disease progression after platinum-containing systemic therapy and whose tumors expressed PD-L1. The primary endpoints were OS and progression-free survival (PFS) and were assessed based on patients with any level of PD-L1 expression (greater than or equal to one percent) and in patients whose tumors express higher levels of PD-L1 (greater than or equal to 50 per cent) – as reflected by tumor proportion score (TPS).

In the total study population (all levels of PD-L1 expression), both doses of Keytruda studied significantly improved OS compared with docetaxel. Specifically, Keytruda resulted in a 29 per cent improvement in OS for the 2 mg/kg dose (HR 0.71 [95% CI, 0.58-0.88; P=0.001]) and a 39 percent improvement in OS for the 10 mg/kg dose (HR 0.61 [95% CI, 0.49-0.75; P<0.001]), compared to docetaxel. Median OS for Keytruda was 10.4 months (95% CI, 9.4-11.9) and 12.7 months (95% CI, 10.0-17.3), respectively, compared to 8.5 months for docetaxel (95% CI, 7.5-9.8).

Among patients with higher levels of PD-L1 expression (a TPS score of 50 percent or greater), OS was superior for both Keytruda doses compared with docetaxel. Specifically, Keytruda improved OS by 46 percent for the 2 mg/kg dose (HR 0.54 [95% CI, 0.38-0.77; P=0.001]) and by 50 percent for the 10 mg/kg dose (HR 0.50 [95% CI, 0.36-0.70; P<0.001]), compared to docetaxel. Median OS for Keytruda (2 mg/kg and 10 mg/kg, respectively) was 14.9 months (95% CI, 10.4 to not reached) and 17.3 months (95% CI, 11.8 to not reached), compared to 8.2 months for docetaxel (95% CI, 6.4-10.7).

Among patients in the total study population treated with Keytruda (2 mg/kg and 10 mg/kg, respectively), median PFS was 3.9 months (95% CI, 3.1-4.1) and 4.0 months (95% CI, 2.6-4.3), compared to 4.0 months for docetaxel (95% CI, 3.1-4.2). Keytruda numerically reduced the risk of progression or death (PFS) at both doses (HR 0.88 [95% CI, 0.73-1.04] for 2 mg/kg; HR 0.79 [95% CI, 0.66-0.94] for 10 mg/kg). PFS results in the overall population were not statistically significant for either dose based on protocol-specified statistical testing requirements.

Patients with higher levels of PD-L1 expression who were treated with Keytruda had significantly prolonged PFS compared to docetaxel (HR 0.58 [95% CI, 0.43-0.77; P=0.001] for 2 mg/kg; HR 0.59 [95% CI, 0.45-0.78; P<0.001] for 10 mg/kg). Among patients treated with Keytruda (pembrolizumab) (2 mg/kg and 10 mg/kg, respectively), median PFS was 5.2 months (95% CI, 4.0-6.5) and 5.2 months (95% CI, 4.1-8.1), compared to 4.1 months for docetaxel (95% CI, 3.6-4.3).

The safety analysis supporting the European approval of Keytruda was based on 2,799 patients with advanced melanoma or NSCLC across three doses (2 mg/kg every three weeks or 10 mg/kg every two or three weeks) in studies KEYNOTE-001, KEYNOTE-002 and KEYNOTE-010 combined. The most common adverse reactions (>10%) with Keytruda were fatigue (24%), rash (19%), pruritus (18%), diarrhea (12%), nausea (11%) and arthralgia (10%). The majority of adverse reactions reported were of Grade 1 or 2 severity. The most serious adverse reactions were immune-related adverse reactions and severe infusion-related reactions.

“We are thrilled that the European Union will now have a new treatment option for certain patients with advanced non-small cell lung cancer who have not responded to chemotherapy,” said Stefania Vallone, president, Lung Cancer Europe. “Lung cancer represents the leading cause of cancer death worldwide, and this milestone underscores the importance of innovation and commitment to developing new treatments that can have a positive impact for patients living with this disease.”

Keytruda is a humanized monoclonal antibody that works by increasing the ability of the body’s immune system to help detect and fight tumor cells. Keytruda blocks the interaction between PD-1 and its ligands, PD-L1 and PD-L2, thereby activating T lymphocytes which may affect both tumor cells and healthy cells.

Keytruda is indicated for the treatment of patients with unresectable or metastatic melanoma.

Keytruda (pembrolizumab) is also indicated for the treatment of patients with advanced non-small cell lung cancer (NSCLC) whose tumors express PD-L1 as determined by an FDA-approved test with disease progression on or after platinum-containing chemotherapy. Patients with EGFR or ALK genomic tumor aberrations should have disease progression on FDA-approved therapy for these aberrations prior to receiving Keytruda.

Keytruda is administered at a dose of 2 mg/kg as an intravenous infusion over 30 minutes every three weeks for the approved indications.