ASCO 2024 abstract movers – Merus convinces, at first

Merus appears to have done enough with its 10-patient strong abstract on petosemtamab plus Keytruda in front-line head and neck cancer to secure its place as one of the winners of Thursday's ASCO abstract drop: its stock closed up 36% on 24 May.

However, the news is less good for Immunocore, whose anti-PRAME project brenetafusp has underwhelmed, especially given the high bar set by Immatics. Friday morning’s 12% slump made Immunocore one of the more significant ASCO fallers, though the shares later recovered, and the move was overshadowed by the collapse in Verastem, which had initially impressed with an ASCO abstract but then crashed 66%.

For Merus a confirmed 50% ORR in petosemtamab’s Keytruda combo trial met analysts’ base case expectations, but this was always going to be about the one additional unconfirmed response, which would have taken the ORR to 60%. Truist Securities analysts wrote: “Given how early it is at the data cutoff we think it is likely that this patient will be confirmed with subsequent follow-up."

Nevertheless, Merus shares later fell when the company press released a more mature data cut, and the results will continue to be scrutinised when presented in full at ASCO. Not only is the dataset tiny, Keytruda plus Erbitux has previously shown a 45% ORR in a 33-patient first-line cohort of a phase 2 academic-sponsored study, so the relevance of the petosemtamab result, and Merus’s ability to replicate it in larger studies, will be debated.

Little gloss

For its part Immunocore put little gloss on a disappointing update concerning its anti-PRAME soluble T-cell receptor IMC-F106C, now known as brenetafusp, focusing on 31 post-checkpoint cutaneous melanoma patients.

Back at ESMO in 2022 the group made the classic mistake of cherrypicking data for an abstract featuring this project across several tumours, and when the 38% ORR cited in the abstract fell to 23% on full presentation its shares fell heavily. Now brenetafusp seems to have disappointed again, its ASCO abstract showing an ORR of 13% in cutaneous melanoma.

True, this is a heavily pretreated population, with all patients having failed on PD-(L)1 therapy, and 88% on CTLA-4 blockade, but the bar has been set high by Immatics, which is developing the anti-PRAME engineered T-cell receptor IMA203. Earlier this month IMA203 yielded a 55% confirmed ORR among 29 evaluable melanoma patients, most of whom had cutaneous disease.

All responses to brenetafusp came among 26 patients deemed to be PRAME expressers. After the January 2022 US approval of Kimmtrac Immunocore needs further wins to support a $2.4bn valuation, and the brenetafusp data don’t seem convincing enough.

Another cell therapy company in need of further wins after an initial approval is Iovance, whose TIL therapy Amtagvi secured US approval at last in February, for PD-(L)1-progressed melanoma.

Now Iovance has front-line use in its sights, and for this reason is running the phase 3 Tilvance-301 Keytruda combo trial. Its ASCO presentation concerns the phase 2 IOV-COM-202 study, which investors see as a benchmark in this setting, and the company yesterday press-released an April data update, versus the ASCO abstract's December 2023 cutoff.

The headline numbers are a 65% ORR, and 30% rate of complete remissions, among 23 patients. This appears favourable on a cross-trial basis versus Keytruda monotherapy in the front-line Keynote-006 study (34% ORR and 6% CR rate) and Opdivo plus Yervoy in Checkmate-067 (50% ORR and 9% CR rate), though this morning Iovance’s stock remained virtually unmoved.

And Candel Therapeutics, which last November slashed 50% of its staff, lost 27% after an initial premarket rise on an ASCO poster abstract covering the oncolytic virus aglatimagene besadenovec in post-checkpoint NSCLC. Though the group claimed “improved survival” this is an uncontrolled study with no comparator, and its abstract revealed no responses.

Selected ASCO share price movers

Source: ASCO abstracts.

Note: this is an updated version of a story published earlier. The ASCO annual meeting takes place in Chicago on 31 May to 4 June.