Merck & Co announced a significant setback in its efforts to expand the use of its flagship immunotherapy drug Keytruda for early-stage head and neck cancer treatment. The Phase 3 KEYNOTE-412 trial, involving 780 patients with newly diagnosed head and neck squamous cell carcinoma (HNSCC), failed to demonstrate statistically significant improvement in event-free survival, its primary endpoint.
Trial Design and Results
The randomized study evaluated Keytruda (pembrolizumab) in combination with cisplatin and radiotherapy, followed by approximately one year of Keytruda maintenance therapy. This regimen was compared against a control arm receiving placebo plus cisplatin and radiotherapy, with placebo during the maintenance phase. Although patients receiving the PD-1 inhibitor showed slight improvements, the difference did not reach statistical significance.
"There have been limited advances for patients with locally advanced HNSCC, and unfortunately, these results suggest that this disease remains very challenging to treat," stated Dr. Eliav Barr, head of global clinical development at Merck.
Current Treatment Landscape
Keytruda currently holds approvals for HNSCC in more advanced disease settings. Since 2016, it has been authorized as a second-line treatment option for patients with recurrent or relapsed metastatic HNSCC following chemotherapy. In 2019, its indication expanded to include first-line treatment for metastatic HNSCC patients, either as monotherapy or in combination with chemotherapy, specifically for tumors expressing elevated PD-L1 biomarker levels.
Challenges in HNSCC Immunotherapy
The KEYNOTE-412 results reflect a broader pattern of challenges in developing immunotherapy treatments for head and neck cancer. Bristol-Myers Squibb's Opdivo (nivolumab) remains the only other immunotherapy approved for HNSCC, limited to second-line use after chemotherapy. Notable failures in this space include BMS's unsuccessful attempt to advance an Opdivo-Yervoy combination therapy to first-line treatment, and Merck KGaA/Pfizer's Bavencio (avelumab), which did not meet its endpoints in a Phase 3 study for locally-advanced HNSCC.
Despite this setback, Merck maintains its commitment to investigating Keytruda-based regimens for earlier stages of HNSCC, acknowledging the significant unmet need in this difficult-to-treat cancer type.
