The Chinese National Medical Products Administration (NMPA) has approved Keytruda (pembrolizumab) as a first-line treatment for locally advanced or metastatic non-small cell lung cancer (NSCLC), Merck (known as MSD outside the U.S. and Canada) announced.

The approval covers patients who have tumors with at least 1% of cells producing the PD-L1 protein, no tumor mutations in the EGFR or ALK genes, and who have received no prior treatment.

An immune checkpoint inhibitor, Keytruda works by preventing the interaction between the PD-1 receptor in immune T-cells and its ligand PD-L1 in cancer cells. This interaction is frequently used by cancer cells to evade anti-tumor immune responses. By preventing it, Keytruda boosts T-cells’ ability to detect and fight tumor cells.

“Keytruda is now the first anti-PD-1 therapy approved in China as both a monotherapy and in combination with chemotherapy in the first-line setting for appropriate patients with advanced non-small cell lung cancer,” Jonathan Cheng, MD, Merck Research Laboratories’ vice president of oncology clinical research, said in a press release.

The approval was based on the results of the KEYNOTE-042 Phase 3 trial (NCT02220894) and an extension of this study in Chinese patients (NCT03850444), in which Keytruda outperformed chemotherapy in extending patients’ lives.

Results of the China extension study were presented for the first time in a poster, titled “KEYNOTE-042 CHINA STUDY: First-line pembrolizumab vs chemotherapy in Chinese patients with advanced NSCLC with PD-L1 TPS ≥1%,” (abstract MA11.02; see page 101), at the IASLC 2019 World Conference on Lung Cancer (WCLC), held recently in Barcelona, Spain.

The international, multi-center, open-label, randomized KEYNOTE-042 study compared the safety and effectiveness of Keytruda and platinum-based chemotherapy in 1,274 patients with locally advanced or metastatic NSCLC. These patients had PD-L1 positive tumors, no tumor mutations in the EGFR or ALK genes, and had received no prior treatment.

The trial’s main goal was to assess whether Keytruda increased overall survival more than chemotherapy in individuals whose tumors had at least 50% PD-L1-positive cells, those with at least 20% PD-L1-positive cells, and in patients with at least 1% PD-L1-positive cells. That reflected the entire study population.

Compared with chemotherapy, Keytruda significantly prolonged the survival of patients whose tumors had at least 50% (20.0 months vs. 12.2. months), 20% (17.7 months vs. 13.0 months), and 1% (16.7 months vs. 12.1 months) PD-L1-positive cells.

The randomized, open-label China extension study had an identical design to the KEYNOTE-042 study. It recruited 262 Chinese people, 92 of whom had participated in KEYNOTE-042, with locally advanced or metastatic NSCLC and PD-L1 positive tumors.

Participants were randomly assigned to receive either 200 mg of Keytruda for up to 35 cycles (128 patients) or chemotherapy for up to six cycles (134 patients). A total of 204 patients (77.9%) had tumors with at least 20% PD-L1-positive cells, and 146 people (55.7%) had at least 50% PD-L1-positive cells.

As in the global study, Keytruda led to a significant improvement in overall survival compared with chemotherapy in all groups of patients included in the extension study. Survival increased from 14 to 20 months in patients with a PD-L1 score of 50% or more; from 13.7 to 20 months in people with 20% or more PD-L1-positive cells; and from 13.7 to 20 months in the entire study population.

Severe and life-threatening adverse events associated with treatment occurred in fewer patients receiving Keytruda (17%) than in those given chemotherapy (68%).

These findings were consistent with previous results of the global KEYNOTE-042 study, supporting the approval of first-line use of Keytruda for PD-L1-positive advanced or metastatic NSCLC in China.

“New treatment options that can help improve survival outcomes are desperately needed in China, as lung cancer remains the leading cause of cancer deaths in this country,” said Yi-Long Wu, honorary director of the Guangdong Lung Cancer Research Institute, and tenured professor of Guangdong Provincial People’s Hospital.

This approval comes a few months after NMPA’s approval of Keytruda in combination with chemotherapy as first-line treatment for metastatic non-squamous NSCLC patients.

“In China, we launched Keytruda one year ago, and already it has had an impact on patient care in the approved indications,” said Joseph Romanelli, MSD’s president in China.