2024 World Conference on Lung Cancer (WCLC) - Posters-P4.11E.11 Dosing Regimen for Acasunlimab (DuoBody-PD-L1x4-1BB) In Combination with Pembrolizumab

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The study investigates the dosing regimen of Acasunlimab (DuoBody-PD-L1x4-1BB), a bispecific antibody, in combination with Pembrolizumab to treat relapsed/refractory metastatic non-small cell lung cancer (R/R mNSCLC). Acasunlimab targets the immune pathways PD-L1 and 4-1BB to elicit antitumor responses. It was studied as a monotherapy and in combination with Pembrolizumab, an anti-PD-1 therapy, to enhance therapeutic effectiveness.<br /><br />In the GCT1046-04 phase 2 trial, different dosing schedules were assessed: Acasunlimab at 100 mg every three weeks (Q3W) as monotherapy and in combination regimens with 200 mg Pembrolizumab every three weeks (Q3W) or with 400 mg every six weeks (Q6W). The trial's endpoint evaluations included overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety metrics such as adverse events (AEs).<br /><br />Modeling analyses indicated that a Q6W dosing schedule might enhance T-cell functionality due to intermittent 4-1BB engagement, promoting better immune responses and tolerability. This schedule showed favorable outcomes, notably a reduced incidence of T-cell dysfunction and more significant proliferation of CD8 memory T cells, compared with the Q3W dosing regimen.<br /><br />Exposure-response analysis linked Q6W dosing with a slightly higher ORR and reduced risk of grade 3 liver-related adverse events compared to Q3W dosing. Faster resolution of liver-related AEs was also seen with the Q6W regimen.<br /><br />Overall, these results suggest that the Q6W dosing regimen of Acasunlimab combined with Pembrolizumab may offer improved durability of clinical responses and safety profile, highlighting its potential as a more effective therapeutic approach in treating R/R mNSCLC. The study was supported by Genmab and BioNTech in collaboration with Merck & Co.

Asset Subtitle

Gaurav Bajaj

Meta Tag

Speaker Gaurav Bajaj

Topic Metastatic NSCLC – Immunotherapy

Keywords

Acasunlimab

DuoBody-PD-L1x4-1BB

Pembrolizumab

non-small cell lung cancer

bispecific antibody

immune pathways

dosing regimen

phase 2 trial

T-cell functionality

exposure-response analysis