ESMO 2024 preview – TIGIT gets its late-breaker

One of the main beneficiaries of this week’s disclosure of ESMO late-breaker titles was the depressed biotech iTeos, whose stock climbed 10% on Tuesday on confirmation that the Galaxies Lung-201 trial of its anti-TIGIT MAb belrestotug has secured such a spot.

That study has been said to have met “predefined efficacy criteria” – a somewhat half-hearted phrase that raised questions over the extent of any success. Scoring an ESMO late-breaker suggests that the data are indeed positive, though enthusiasm should be tempered by the fact that another late-breaker features a failed trial of AstraZeneca’s Truqap.

Of course, it’s possible that investigators from the Truqap trial, CAPitello-290, have found a new subgroup on which to spin it positively, but ESMO has historically featured failures as well as successes in prestigious sessions. CAPitello-290, in first-line triple-negative breast cancer, was toplined a bust for OS in all-comers as well as in cancers with PIK3CA/AKT1/PTEN alterations.

For followers of the TIGIT mechanism iTeos’s belrestotug is one of the few remaining hopes, and enthusiasm has been given a boost by GSK, its big pharma partner, starting the phase 3 Galaxies Lung-301 study – in the first-line NSCLC setting of Galaxies Lung-201. GSK licensed belrestotug for $625m in 2021, so much is riding on the ESMO late-breaker.

Lag3

Another immuno-oncology mechanism with lots to prove is Lag3, and beyond the regulatory success in first-line melanoma of Bristol Myers Squibb’s Opdualag there has been little to shout about.

Relativity-104, Opdualag’s long-delayed phase 2 NSCLC study, will feature in an ESMO late-breaker, and there’s a common theme here with belrestotug: Opdualag’s phase 3 trial in this NSCLC setting, Relativity-1093, is also just now getting under way.

Immutep’s Lag3 project eftilagimod, has also scored an ESMO late-breaker; this is a soluble Lag3 protein rather than being an antagonist MAb like Opdualag’s Lag3 component, relatlimab. The subject of eftilagimod’s late-breaker is the failed Tacti-003 trial in first-line head and neck cancer, so like with CAPitello-290 ESMO is choosing to highlight negative data.

Combos and others

Meanwhile, in immuno-oncology combos the focus will fall on late-breakers featuring Jiangsu Hengrui’s anti-PD-L1/TGFβ fusion protein retlirafusp alfa, and Qilu’s QL1706, a fixed-dose combination of iparomlimab and tuvonralimab.

The former is weighed down by disappointments among rivals combining activity on TGFβ and immune checkpoints, most notably Merck KGaA/GSK’s bintrafusp alfa, which used the same approach as retlirafusp alfa. Data on the Jiangsu Hengrui molecule will come from a phase 3 first-line gastric cancer study; a separate phase 3 test, in the perioperative setting, was terminated.

Qilu describes QL1706 as a “bifunctional Mabpair” product, though this still comprises two separate antibodies, against PD-1 and CTLA-4. Last year’s ESMO brought data in cervical cancer, and this year will be the turn of first-line liver cancer; both trials included a combo with Avastin.

And for small biotech watchers perhaps the most intriguing ESMO late-breaker concerns Scorpion’s STX-478, a mutant-selective PI3Kα inhibitor whose development the private company now ranks above former lead assets targeting EGFR-mutated NSCLC.

The latter is an extremely competitive space that has seen setbacks at Black Diamond, Blueprint, Theseus and others. Selective PI3Kα inhibition, however, has come into focus, with Lilly recently persevering in its quest to identify a new H1047R mutant-selective project after the discontinuation of LOXO-783.

Selected ESMO 2024 late-breakers*

Note: *excludes those at the presidential session, covered separately. Source: ESMO.

ESMO will take place in Barcelona, Spain, on 13-17 September 2024.