Today, the FDA approved the immunotherapy drug pembrolizumab (Keytruda®), made by Merck, as second-line treatment for patients with lung cancer, the leading cause of cancer-related death in the U.S. and the world. Pembrolizumab is an immunotherapy drug known as a checkpoint inhibitor that acts to “release the brakes” on the immune system, allowing it to mount a stronger and more effective attack against cancer. The particular braking molecule targeted by this drug is called PD-1.
Pembrolizumab is approved for the treatment of both squamous and non-squamous non-small cell lung cancer (NSCLC) that is no longer responding to standard-of-care chemotherapy. Together, these types account for the vast majority of lung cancer cases. Another PD-1-targeting drug, nivolumab (Opdivo®), made by Bristol-Myers Squibb, was approved earlier in 2015 as second-line treatment of squamous cell NSCLC.
Today’s approval was based on results from a phase I trial (KEYNOTE-001) that looked at the drug’s safety in 550 patients with advanced NSCLC. The efficacy of the drug for the treatment of chemo-resistant lung cancer was shown in a smaller group of 61 patients with this condition.
The FDA approved pembrolizumab under its accelerated approval program, which allows early approval of promising drugs based on surrogate endpoints that are reasonably likely to predict clinical benefit to patients. In this case, the surrogate endpoint was overall response rate (ORR)—the percentage of patients who experienced complete and partial shrinkage of their tumors. Tumors shrank in 41 percent of patients treated with pembrolizumab and the effect lasted between 2.1 and 9.1 months. An improvement in overall survival (OS) has not yet been demonstrated. The FDA awarded pembrolizumab a “Breakthrough Therapy” designation in October 2014 for the treatment of NSCLC.
In order to be eligible for treatment with this drug, patients must have tumors that contain a protein marker called PD-L1. This protein, made by some cancer cells and immune cells, is the binding partner of the PD-1 “brake” on immune system. Pembrolizumab acts to block this interaction, allowing the immune system to remain active and fight the cancer. Data from the study presented at this year’s meeting of the American Association of Cancer Research (AACR) indicate that patients with higher levels of PD-L1 in their tumors tend to respond better.
Lung cancer experts lauded today's approval. “This important news means that we now have a new immunotherapy option to help patients with squamous and non-squamous metastatic non-small cell lung cancer with disease progression on or after platinum-containing chemotherapy and whose tumors express PD-L1,” said Naiyer Rizvi, M.D., a lung cancer immunotherapy expert at Columbia University Medical Center, and a principal investigator for the pembrolizumab clinical trials, in a press release. “The durability of response with immune checkpoint inhibitors is exciting and has given new options for our patients.”
The FDA’s approval of pembrolizumab comes just a day after the regulatory agency approved a 2-drug immunotherapy combination for patients with advanced melanoma. A big week for immunotherapy and a big week for patients!