Merck, Pfizer’s Bavencio flunks head and neck cancer trial

Merck KGaA and Pfizer’s checkpoint inhibitor Bavencio has failed a phase 3 trial in head and neck cancer, blocking their hopes of extending use of the latecomer drug.

The JAVELIN Head and Neck 100 study compared Bavencio (avelumab) to placebo given on top of chemoradiotherapy in previously-untreated patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN).

The study was abandoned after it became clear it was unlikely to show a significant improvement on the time to disease progression or death for the checkpoint inhibitor compared to control.

Head and neck cancer is the sixth most common cancer in the world, with almost two-thirds of patients diagnosed when they have locally advanced disease, and there have been few treatment advances for this group over the last decade, said the two companies.

PD-L1 inhibitor Bavencio is already approved to treat a rare form of skin cancer called Merkel cell carcinoma and as a second-line therapy for urothelial carcinoma – the most common form of bladder cancer – and as a combination with Pfizer’s Inlyta (axitinib) for previously-untreated advanced renal cell carcinoma.

Approval in first-line SCCHN treatment would open up a sizeable new patient population for the drug, given there are around 150,000 new cases diagnosed in the US, Japan and Europe a year, but the trial failure scuppers Merck and Pfizer’s ambitions in this area for the time being.

The two partners are continuing to look at combinations of Bavencio with other drugs in the SCCHN setting, including a phase 3 trial (REACH) pairing the PD-L1 inhibitor with Merck’s antibody drug Erbitux (cetuximab) in patients with locally advanced tumours.  

Other checkpoint inhibitors are already approved for SCCHN, but these are so far limited for use in only metastatic disease. JAVELIN Head and Neck 100 is the first late-stage trial to report data for a checkpoint inhibitor in combination with chemoradiotherapy in locally-advanced SCCHN, according to Merck and Pfizer.

Last year, Merck & Co/MSD’s PD-1 inhibitor Keytruda (pembrolizumab) became the first drug in the PD-/PD-L1 category to be given a green light by the FDA as a first-line monotherapy for metastatic or unresectable PD-L1-positive SCCHN and with chemotherapy for ‘all-comer’ patients, based on the results of the KEYNOTE-048 trial.

Keytruda is also approved for use alongside chemotherapy for people with SCCHN that has returned or spread despite prior treatment, as has Bristol-Myers Squibb’s PD-1 inhibitor Opdivo (nivolumab).

Germany’s Merck has been predicting a sizeable uptick in sales for Bavencio in 2020 after reporting just €103 million in sales for the drug last year, while co-marketing partner Pfizer hasn’t revealed sales in 2019.

Merck books the bulk of Bavencio sales however under the terms of its 2014 alliance with Pfizer on the drug, which saw the US drugmaker pay $850 million upfront for rights and up to $2 billion in milestone payments. It expects the increase to come largely from increased use in bladder and kidney cancer.

Bavencio has previously also missed the mark in late-stage trials involving patients with non-small cell lung cancer (NSCLC), ovarian cancer and stomach cancer.