Bid to expand Keytruda use in head and neck cancer therapy fails

While immunotherapies have transformed treatment of many types of cancer, they do sometimes fail to have an impact – as Merck & Co has just observed in a study of Keytruda in head and neck cancer.

The PD-1 inhibitor missed the mark in the phase 3 KEYNOTE-412 trial in 780 newly-diagnosed patients with head and neck squamous cell carcinoma (HNSCC), a notoriously hard-to-treat form of cancer.

The study compared Keytruda (pembrolizumab) given with cisplatin and radiotherapy – followed by maintenance therapy with Keytruda for around a year – to placebo plus cisplatin and radiotherapy and placebo during the maintenance phase.

The primary endpoint of the study was even-free survival, but there was no statistically significant difference between the groups on this measure even though patients on the PD-1 therapy did slightly better, said Merck in a statement.

Keytruda has been approved since 2016 as a second-line option after chemotherapy for patients with more advanced disease, i.e. recurrent or relapsed HNSCC that has metastasised to other parts of the body

In 2019, it moved into the first-line setting for these patients, given either alone or in combination with chemo in patients with metastatic HNSCC whose tumours express elevated levels of the PD-L1 biomarker.

The outcome of KEYNOTE-412 dashes Merck's hopes of extending Keytruda's indications in HNSCC to non-metastatic disease in an all-comer population, regardless of PD-L1 status.

"There have been limited advances for patients with locally advanced HNSCC, and unfortunately, these results suggest that this disease remains very challenging to treat," said Eliav Barr, Merck's head of global clinical development.

At the moment the only other immunotherapy approved to treat HNSCC is Bristol-Myers Squibb's Opdivo (nivolumab), which can be used as a second-line option after chemotherapy.

BMS' attempts to move into the first-line setting with a combination of Opdivo and CTLA4 inhibitor Yervoy (ipilimumab) were unsuccessful, while Merck KGaA/Pfizer's Bavencio (avelumab) also missed the mark in a phase 3 study in locally-advanced HNSCC.

Merck says it is committed to "investigating Keytruda-based regimens for this debilitating type of cancer in earlier stages of disease."

That includes the phase 3 KEYNOTE-689 study of the immunotherapy as neoadjuvant and adjuvant treatment of locally advanced HNSCC that can be treated with surgery, which is scheduled to complete in 2025.