SITC 2024 preview – duelling TIGIT duds

The failed Keyvibe-008 study of Merck & Co's anti-TIGIT MAb vibostolimab has unexpectedly been selected to feature as an an oral presentation at a late-breaking clinical trial session of the SITC conference, which starts this week.

A second surprise is Arcus/Gilead's rival anti-TIGIT MAb, domvanalimab, whose discontinued ARC-10 trial has secured another late-breaking SITC presentation, though only as a poster. Among antibody approaches the conference's other late-breaking posters include a CCR8 blocker and two bispecifics that hit Claudin18.2; both approaches are of interest across biotech.

The rise of CCR8 blockade has been low-key, but it has seen buy-in from the likes of Amgen, Roche, AbbVie and Bristol Myers Squibb. The late-breaking focus at SITC (Society for Immunotherapy of Cancer) meeting will be a phase 1 solid tumour study of QLP2117, a MAb originated by China's Qilu Pharmaceutical. Positive data could lend CCR8 antagonism much-needed validation.

Underwhelming TIGIT

Such validation has been hard to come by in the case of TIGIT blockade, an approach that has already hugely underwhelmed, notwithstanding the promise that remains most notably in liver cancer.

Merck's vibostolimab, given with chemo as part of a fixed-dose combo with pembrolizumab, blew up in first-line SCLC when its Keyvibe-008 trial was halted for futility in August. The SITC late-breaker will thus offer a postmortem, and a particular focus will fall on immune system-mediated adverse events, said to have increased when the Keyvibe-008 flop was revealed.

Gilead/Arcus's Arc-10 trial hasn't formally been deemed a failure, but its discontinuation in January strongly suggests this outcome. Arc-10 tested domvanalimab plus zimberelimab in first-line PD-L1-high NSCLC, a setting where TIGIT has disappointed, and full data at SITC will show just how bad the data were to prompt the companies' decision.

Selected SITC 2024 late-breaking clinical data featuring MAbs

Note: *oral presentation; the rest are late-breaking posters. Abstract content is embargoed until 9am EST on 5 Nov.

Meanwhile, Claudin18.2 blockade is one of biotech's most crowded spaces, and was validated at last with last month's approval of Astellas's Vyloy.

SITC will see data on Q-1802, a Claudin18.2 x PD-L1 bispecific from QureBio, and givastomig, I-Mab's Claudin18.2 x 4-1BB co-stimulated approach; the latter is notable for being the subject of a clinical trial collaboration with Bristol, which recently ended a separate Claudin18.2-based tie-up with LaNova Medicines, though other approaches using co-stimulation haven't fared well.

Clinical data on such high-profile targets belie the fact that SITC remains at heart a conference focused on early findings from novel immunotherapies. Notable in this category are late-breaking posters on BTN1A1 blockade and CFH (complement factor H), from STCube and Grid Therapeutics respectively.

OncologyPipeline reveals no other anti-BTN1A1 MAbs in development, while Alchemab Therapeutics has the only other anti-CFH MAb, having presented preclinical data at last year's SITC. Grid is one of several private US biotechs that could enjoy a higher profile thanks to SITC, another being OncoResponse, whose anti-LILRB2 (anti-ILT4) MAb OR502 could rival Merck/Agenus's AGEN1571 and Pfizer's PF-07826390.

SITC 2024 takes place in Houston, Texas on 6-10 November.