ASCO: Merus bispecific garners attention after abstract drop

Among the myriad of new studies highlighted in the newly published ASCO abstracts, Merus’ seems to have struck a chord with its phase 2 trial of bispecific antibody petosemtamab in head and neck cancer.

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 head and neck squamous cell carcinoma (HNSCC). Netherlands-based Merus is hoping to be the first to bring a drug in the class through development.

The abstract shows that out of 10 patients who were evaluable for efficacy at the data cut-off last November, there was one complete response, five partial responses, and three patients with stable disease, meaning only one subject showed no response to the regimen. There was also a “favourable” safety profile in 26 patients enrolled as of the cut-off date, with no significant overlapping toxicities observed, according to the study investigators. Updated results will be presented when ASCO starts next week.

Shares in Merus on the Nasdaq rose sharply in pre-market trading after the drop, reflecting that there are few effective therapies for this type of cancer and the petosemtamab/Keytruda combination’s 60% response rate seems to be way ahead of what would be expected with current regimens.

At last year’s AACR cancer congress, Merus reported a near-36% response rate with petosemtamab as a monotherapy in previously treated HNSCC patients, setting up a phase 3 trial in that setting that is due to start shortly. Earlier this month, the FDA granted a breakthrough designation to the drug for recurrent or metastatic HNSCC with disease progression after platinum-based chemotherapy and PD-1/PD-L1 antibody treatment.

The combination data is a key development for Merus, not least because Keytruda is a well-established first-line therapy for HNSCC, having been approved for that indication in 2019.

“We believe petosemtamab continues to demonstrate potential best-in-class safety and efficacy in head and neck cancer,” said Merus' chief executive, Bill Lundberg.

“We are encouraged with the well-tolerated safety profile of the combination of petosemtamab and pembrolizumab, particularly with a low rate of grade 3 or greater adverse events, and a low rate of infusion-related reactions observed,” he added.

Merus is also carrying out a study to identify the best dose of petosemtamab (1,100 mg or 1,500 mg) to take forward into phase 3, with results due later this year, and is planning a study of the drug in combination with chemo as a second-line treatment for colorectal cancer – another disease that has seen few therapeutic advances in recent years.