- Merck & Co.’s cancer immunotherapy Keytruda has come up short in two Phase 3 trials, one in prostate cancer and another in advanced lung cancer, the company said Tuesday, limiting two avenues for further widening of the drug’s use.
- In prostate cancer, Keytruda in combination with another drug called Xtandi and hormone therapy didn’t stop progression or improve survival in advanced patients better than Xtandi and hormone therapy alone. In lung cancer, Keytruda and chemotherapy didn’t improve survival in advanced patients with a certain mutation following treatment with a targeted therapy.
- With biosimilar competition arriving for AbbVie’s inflammatory disease drug Humira, Keytruda is on track to become the world’s top-selling drug. Broadening its use remains important for Merck as Keytruda nears the end of its own patent-protected exclusivity, which is expected to come in 2028.
Merck’s strategy is centered on managing Keytruda’s life cycle and filling its pipeline to offset the eventual entry of biosimilar competitors. Continued expansion of Keytruda’s use is one part of that strategy, and the drugmaker is usually successful at it.
In the case of prostate cancer, however, that strategy is looking doubtful. The KEYNOTE-641 trial enrolled men with prostate cancer whose disease had spread and become resistant to testosterone-suppressing treatment. It tested a combination of Keytruda, Xtandi and a hormone-suppressing treatment against Xtandi and hormone suppression alone.
After evaluating the data, study monitors found the Keytruda combination wasn’t slowing the spread of tumors any better than the comparison treatment, and that patients receiving the Keytruda combination weren’t living any longer.
No other drug in Keytruda’s class has won U.S. approval yet in this disease. Pfizer and Astellas’ Xtandi and another drug called Zytiga from Johnson & Johnson were launched more than a decade ago and substantially improved patients’ outlook in what is typically a slow-progressing disease. More recently, drugs called PARP inhibitors have improved upon Xtandi and Zytiga, with AstraZeneca awaiting a Food and Drug Administration decision on Lynparza plus Zytiga and Pfizer having succeeded in late-stage testing of a Talzenna and Xtandi combination.
In lung cancer, where Keytruda has become the biggest selling drug as a first-line treatment that helps most patients, Merck has been seeking to extend its reach. Specifically, the drugmaker is studying the medicine in patients whose tumors have epidermal growth factor receptor mutations, which account for about 10% to 15% of all non-small cell lung cancer. In first-line treatment, these patients usually get targeted drugs like Roche’s Tarceva or AstraZeneca’s Tagrisso, but their cancer can become resistant to those therapies.
In KEYNOTE-789, Merck tested Keytruda plus a chemotherapy combination against chemotherapy alone in people whose lung cancer had progressed on targeted therapy. At an interim analysis, the Keytruda combination hadn’t delayed progression, and on Tuesday, Merck revealed it didn’t help patients live longer as defined by the statistical test in KEYNOTE-789.
“Science is rarely a straight line, and while we are disappointed in these study results, our research to investigate Keytruda in many difficult-to-treat types of cancer continues in earnest,” said Eliav Barr, Merck’s head of global clinical development, in a statement.