Inhibrx cans co-stimulatory candidate

Outside of Car-T, adding co-stimulatory domains to cancer therapies has not borne much fruit. In the latest casualty in this space, Inhibrx yesterday slipped out the termination of INBRX-105, its anti-PD-L1 x 4-1BB bispecific, in its fourth-quarter results release. The group cited disappointing data from dose-expansion cohorts of a phase 2 solid tumour trial. A look at the pipeline shows several active players, most notably Genmab, which is keeping faith with its contender, acasunlimab, despite admitting at last year’s London Jefferies meeting that it had not seen sustained responses with monotherapy in second-line lung cancer. The company is pinning its hopes on combining acasunlimab with Keytruda – a curious approach given the overlapping mechanisms of action – and a phase 3 trial is slated to start this year. Meanwhile, Roche also has a couple of projects with a 4-1BB component, but neither targets PD-(L)1: RO7122290 hits FAP while englumafusp alfa takes aim at CD19. Things haven’t gone well for the other main co-stimulatory domain, CD28: in 2022 Alpine Immune Sciences discontinued its CD28 costimulator and dual checkpoint inhibitor davoceticept following two patient deaths, and shifted focus to autoimmune and inflammatory disease.

Anti-PD-(L)1/4-1BB pipeline

Source: OncologyPipeline.