Merck’s Phase III trial studying Keytruda (pembrolizumab) for unresected locally advanced head and neck squamous cell carcinoma (HNSCC) failed to meet the primary endpoint.
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Merck‘s Phase III trial on Keytruda (pembrolizumab) for unresected, locally advanced head and neck squamous cell carcinoma (HNSCC) failed to meet the primary endpoint of event-free survival (EFS) — an atypical result given that the drug is already approved for several indications.
In the final analysis of the Phase III KEYNOTE-412 trial (randomized, double-blind), patients who received Keytruda showed an improvement in EFS compared to placebo plus chemoradiation therapy. However, Keytruda was unable to meet the statistically significant EFS metric according to the pre-specified plan. The drug’s safety profile remained consistent with previous studies in HNSCC.
As of 2020, there were over 930,000 cases of head and neck cancers worldwide and more than 465,000 related deaths. In the U.S., scientists predict that there will be over 66,000 new cases diagnosed and over 15,000 deaths in 2022 alone.
This is not the first time Keytruda has failed to demonstrate efficacy in a cancer trial, in spite of being the approved checkpoint inhibitor drug for numerous indications. In 2021, Merck had to voluntarily withdraw Keytruda after it failed to meet its primary endpoint in the treatment of metastatic small cell lung cancer. The U.S. Food and Drug Administration found that Keytruda, along with drugs from other companies, had gone through the accelerated pathway without fulfilling post-marketing requirements.
This is Merck’s second clinical setback in one week, as the company announced a halt of its Phase III trial studying Lynparza for colorectal cancer earlier this week.
“There have been limited advances for patients with locally advanced HNSCC, and unfortunately, these results suggest that this disease remains very challenging to treat. We are proud of the significant role Keytruda plays in the treatment of certain later stages of HNSCC, and we are committed to investigating Keytruda-based regimens for this debilitating type of cancer in earlier stages of disease. We are grateful to the patients and investigators for their participation in this study,” Dr. Eliav Barr, senior vice president, head of global clinical development and chief medical officer at Merck Research Laboratories, said in a statement.
Keytruda is an anti-programmed death receptor-1 (PD-1) therapy. The drug, combined with platinum and fluorouracil, is indicated for the first-line treatment of patients diagnosed with metastatic or unresectable, recurrent HNSCC. As a single agent, it is indicated for patients with the same disease whose tumors express PD-L1 and patients with disease progression during or after platinum-containing chemotherapy.
Keytruda is approved as a monotherapy and in combination with other drugs for patients with metastatic or unresectable, recurrent HNSCC in China, Europe, Japan and the United States among other countries. There are currently over 1,700 ongoing studies involving the drug across a wide range of settings. Merck alone has around 20 ongoing registrational trials for multiple types of cancer.
In the U.S., Keytruda is indicated for patients with unresectable or metastatic melanoma, relapsed or refractory classical Hodgkin lymphoma, refractory primary mediastinal large B-cell lymphoma, locally advanced or metastatic urothelial carcinoma, Bacillus Calmette-Guerin-unresponsive, high-risk, non-muscle invasive bladder cancer and several others.
