ASCO 2024 preview – Merus’s home run remains unconfirmed

Whether Merus’s phase 2 study of petosemtamab has hit the sellside’s bull scenario or just met the base case comes down to how strictly you define a remission. One of the six responses in petosemtamab’s first-line head and neck cancer Keytruda combo trial hasn’t been confirmed, according to an ASCO abstract that has just gone live.

Though the results concern just 10 patients, for biotech investors they represent one of ASCO’s most closely watched datasets. Merus’s bispecifics strategy has had a recent setback, with the EGFR x cMet targeting MAb MCLA-129 disappointing in NSCLC in December, but since then the group’s stock has nearly doubled, largely on the promise of petosemtamab.

In recent weeks analysts from Needham, Truist and BMO all set 50% ORR as a likely base case for Merus to hit in the phase 2 trial, while also writing that 60% was possible in a knockout scenario. Notably, however, none of the banks stated whether their expectations related to all responses or just those that were confirmed on second scan.

November cutoff

The issue will remain live at ASCO, where more detail, and perhaps a more mature dataset, might be given. For now all investors have to go on is the abstract, unveiled today along with all non-late-breaking ASCO presentations, and concerning a 6 November 2023 cutoff.

Among the 10 front-line patients eligible for Keytruda, who were given Keytruda plus petosemtamab, there was one confirmed complete remission and two confirmed partial responses. Three further PRs were unconfirmed at the cutoff date, but two of these were confirmed subsequently.

On a purely mathematical basis therefore this gives a 50% confirmed ORR, meeting baseline expectations, while 60%, including the unconfirmed response, is a home run. The basis for such benchmarks was Keytruda’s monotherapy activity – 19% ORR in PD-L1-positive first-line patients – plus the 37% ORR number petosemtamab had put up in second-line head and neck cancer.

Safety positive

If the efficacy data do give cause for celebration, then another positive sign will be seen on petosemtamab’s toxicity side. Earlier Merus studies had seen 75% of patients reporting infusion reactions, but ASCO’s 26-patient safety dataset shows these occurring in 27% of patients at any grade, or in 4% at grade 3. 

The thinking behind petosemtamab is that it combines the anti-EGFR mechanism of Lilly’s Erbitux with targeting of the leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), which is thought to cause EGFR internalisation and degradation, increasing potency. An earlier phase 1/2 study had set 1.5mg as the recommended phase 2 dose, and this was given in the current trial.

With Merus now valued at $2.6bn expect the sellside to perform extensive mathematical gymnastics over this 10-patient dataset.