Merck’s Keytruda Fails Pivotal Bladder Cancer Study, Sinks First-Line Hopes

Xconomy New York — 

Merck’s blockbuster cancer immunotherapy pembrolizumab (Keytruda) has failed a pivotal study testing it in an aggressive form of bladder cancer.

The Merck (NYSE: MRK) drug  was being evaluated in urothelial carcinoma, a form of cancer that starts in the cells that line the inside of the bladder. It’s the most common type of bladder cancer, and pembrolizumab is already approved to treat it when it can’t be surgically removed or when patients need an alternative to chemotherapy. The failure in the latest bladder cancer test dashes the Kenilworth, NJ-based pharmaceutical giant’s hopes of expanding use of the drug to make it a first choice for treating bladder cancer that has advanced or spread.

The Phase 3 study, KEYNOTE-361, enrolled 1,010 patients randomly assigned to receive pembrolizumab plus chemotherapy, pembrolizumab alone, or chemotherapy. The goals were to show improvement in how long patients lived overall as well as how long they lived without the cancer worsening.

Patients in the group that received the Merck drug plus chemotherapy showed improvement on both study measures compared to those treated with chemotherapy alone. But the change was not enough to be statistically significant, Merck reported after the market close Tuesday. The company added that the patient group that received pembrolizumab alone was not formally evaluated because the study goals were not reached in the drug combination arm of the study.

Pembrolizumab is a type of immunotherapy called a checkpoint inhibitor. It was designed to block the PD-1 pathway, which cancers use to hide from the immune system. Since notching its first FDA approval in melanoma in 2014, the drug has gone on to win the regulatory nod for a slew of cancers. For 2019, Merck reported that pembrolizumab tallied $11.1 billion in sales, a 55 percent increase over the prior year.

Merck has been trying to expand use of pembrolizumab, by itself and in combination with other cancer therapies. Those efforts include adding on to the approved applications of the drug in bladder cancer. Rival companies are also trying to expand use of their immunotherapies to first-line treatment of bladder cancer. Last year, Roche reported Phase 3 data showing that its drug, atezolizumab (Tecentriq), beat chemotherapy alone in treating patients whose urothelial cancer has advanced or spread. But there have also been failures. In March, AstraZeneca (NYSE: AZN) reported that its drug durvalumab (Imfinzi) flunked a Phase 3 test in urothelial cancer that can’t be removed surgically.

Merck says it is continuing to test pembrolizumab by itself and in combination with other therapies in bladder cancer, including metastatic muscle-invasive bladder cancer and non-muscle invasive bladder cancer.

In the pembrolizumab clinical trial results released Tuesday, Merck said that the safety profile of the drug was consistent with earlier studies. The pharmaceutical giant said the study results will be presented at an upcoming medical meeting.

Image: iStock/Michael Vi