Genmab presses on with acasunlimab

Genmab recently lost BioNTech as a partner on its anti-PD-L1 x 4-1BB bispecific acasunlimab, but it’s pushing into phase 3 alone, according to a recent listing on clinicaltrials.gov. The Abbil1ty NSCLC-06 study will compare acasunlimab plus Keytruda versus docetaxel in PD-L1-positive NSCLC patients progressed on PD-(L)1 inhibitors and platinum chemo. The primary endpoint is overall survival, while PFS and ORR are secondaries. As expected, the group has opted for acasunlimab dosed at 100mg plus Keytruda 400mg once every six weeks, the regimen that performed best in phase 2, producing a confirmed ORR of 17% and median OS of 17.5 months. This gives Genmab a benchmark to hit, but side effects will be closely watched; in this dosing arm in phase 2, 18% of patients had liver-related adverse events, and there was a 25% discontinuation rate. Combining a PD-L1-targeting therapy with Keytruda might seem a strange strategy, but BioNTech previously explained that acasunlimab had been optimised to hit 4-1BB, so needed extra PD-(L)1 inhibition for maximum effect. However, targeting co-stimulatory domains like 4-1BB hasn’t gone well before, with Inhibrx’s discontinuation in February of the similarly acting INBRX-105. Remaining competitors include Nanjing Leads Biolabs and Merus.

Phase 3 trial of acasunlimab

Source: clinicaltrials.gov.