ASCO 25: Merus bispecific scores again in HNSCC

For the second year running, data at ASCO on Merus' bispecific antibody petosemtamab in head and neck cancer has drawn the eye, as the company talks up its potential to become a new standard of care.

The results show an impressive 63% objective response rate (ORR) in 43 evaluable patients in a phase 2 trial, as of a 27th February data cutoff, along with 79% overall survival (OS) rate at 12 months and median progression-free survival (PFS) of nine months.

The study is looking at the combination of petosemtamab – which targets EGFR and LGR5 – with MSD's PD-1 inhibitor Keytruda (pembrolizumab) as a first-line treatment for metastatic, PD-L1-positive head and neck squamous cell carcinoma (HNSCC). The drug showed efficacy in patients with both HPV-positive and HPV-negative disease, according to Netherlands-based Merus.

Shares in the company rocketed as investors responded to the data and the potential for petosemtamab to become the first drug in the class to make it through development and onto the market. If approved, it would offer an improvement over Keytruda as a standard way to treat people newly diagnosed with HNSCC.

At the same time, shares in another company developing a bispecific for this type of cancer, Boston-based Bicara Therapeutics, fell sharply after an abstract of a phase 1/1b trial of its EGFRxTGF-beta drug ficerafusp alfa pointed to a 64% ORR in an HPV-negative population only.

Merus' chief executive, Bill Lundberg, said: "By essentially every metric, we believe these interim data are significantly better than pembrolizumab monotherapy, the control arm of our ongoing phase 3 trial, and underscore the opportunity petosemtamab holds to become a new standard of care, if approved, in head and neck cancer."

The company is hoping to share top-line data from "one or both" of its phase 3 trials of petosemtamab in 2026, he added.

The LiGeR-HN1 study started dosing patients last September and is comparing first-line use of the bispecific plus Keytruda to Keytruda alone in PD-L1-positive HNSCC. Meanwhile, the LiGeR-HN2 trial, comparing petosemtamab to investigators' choice of methotrexate, docetaxel, or cetuximab as a second- or third-line therapy for relapsed/refractory HNSCC patients, started dosing last summer. Both indications have breakthrough designations from the FDA.

Merus thinks petosemtamab has blockbuster sales potential across HNSCC and other potential indications, including metastatic colorectal cancer, a programme that could yield initial clinical data before the end of the year.