ASCO 2024 preview – with more patients Merus claims better efficacy

It took just five days from ASCO unveiling an abstract covering some promising but very preliminary results on Merus’s petosemtamab to the company press releasing a more mature data cut that suggests a home run scenario.

The findings, concerning a 6 March data cutoff, have effectively scooped Merus’s ASCO presentation on 3 June. They show petosemtamab’s headline confirmed ORR number, from a phase 2 Keytruda combo trial in first-line head and neck cancer, climbing from 50% to 62%, beating the sellside’s 60% bar for the bull case. Still, important detail on durability remains under wraps for now.

Moreover, Merus stock fell 9% today, suggesting that investors had become too exuberant last week. The market might also have been spooked by petosemtamab’s safety profile; while this remains better than in Merus’s earlier trials, a deterioration is evident in the results’ latest iteration.

Confirmed ORR

The latest data cut comes from 26 patients, in whom one confirmed complete remission was seen, plus 15 partial responses (three of these unconfirmed).

With Merus stating that all three unconfirmed PRs were confirmed on second scan after the 6 March cutoff a seemingly impressive 62% ORR can be claimed. Merus goes further, seeking to exclude two patients (one revoked consent and the other withdrew owing to toxicity) and thus citing a 67% ORR, but strictly speaking the baseline number for efficacy-evaluable subjects is 26.

Either way, this is an advance on the 50% confirmed ORR reported last week from an ASCO abstract concerning a 6 November cutoff date. That caused Merus stock to surge 36% on Friday, yielding a market cap of around $3.5bn – a surprisingly strong rise given that the results came from just 10 patients.

Other important detail disclosed today includes a benefit holding steady in PD-L1-low (ORR 60%) and PD-L1-high (ORR 71%) patients, and responses being seen in HPV-negative as well as positive tumours. 

With the larger dataset Merus might have hoped to put to bed fears that it’s been overbought. This type of early data release is permitted by ASCO, and was done last week by Iovance, for instance; once the abstract embargo has passed it’s down to the sponsor when to reveal full data.

Infusion reactions

However, the 45-patient strong safety dataset shows a higher rate of infusion-related reactions than in the abstract: 38% at any grade or 7% at grade 3, versus the earlier 27% and 4% respectively. The other note of caution on safety is the one patient discontinuation due to unspecified toxicity before completing two treatment cycles. 

Petosemtamab is a bispecific MAb combining the anti-EGFR mechanism of Lilly’s Erbitux with targeting of LGR5, which is thought to cause EGFR internalisation and degradation, and thus increase potency.

Its toxicity will remain in focus when the data are presented in full at ASCO on Monday, as will the question of how long-lasting the responses have been. As regards durability or relapses, all Merus has said is that 14 of the 16 responders remain on study, but the median follow-up among all 45 is only 3.6 months.

No swimmers plot has been provided so far.

How petosemtamab's 1st-line head & neck Keytruda combo dataset has evolved

Source: ASCO & company release.