Genmab A/S and BioNTech SE announced initial data from the Phase 2 GCT1046-04 trial (NCT05117242) evaluating acasunlimab (DuoBody-PD-L1x4-1BB), an investigational bispecific antibody also known as GEN1046/BNT311, as monotherapy and in combination with pembrolizumab in patients with PDL(1)-positive mNSCLC who had disease progression following one or more prior lines of anti-PD(L)1 containing treatment. The results showed a 12-month overall survival (OS) rate of 69%, a median overall survival (mOS) of 17.5 months, and a 30% overall response rate (ORR); (confirmed ORR 17%) at time of data cut-off in patients treated with the combination of acasunlimab and pembrolizumab every six weeks. The findings were presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting, being held in Chicago, IL and virtually, May 31-June 4, 2024.

The Phase 2 study randomized a total of 113 patients in three arms, evaluating acasunlimab alone (Arm A) and in combination with pembrolizumab (Arms B and C). The objective response analysis was conducted for 62 centrally confirmed PD-L1-positive efficacy-evaluable patients. The overall survival was evaluated in all centrally confirmed PD-L1-positive patients (n=80).

Arm A showed a median overall survival rate (mOS) of 5.5 month, 50% disease control rate (DCR) and 31% ORR (confirmed ORR 13%) in patients being treated with acasunlimab alone (Arm A), an 8.6 month mOS, 59% DCR and 21% ORR (confirmed ORR 18%) with treatment of acasunlimab in combination with pembrolizumab every three weeks (Arm B) and a 17.5 mOS, 75% DCR and 30% ORR (confirmed ORR 17%) when the combination was administered every six weeks (Arm C). Anti-tumor activity was observed in patients with tumor proportion score (TPS) of 1- 49% and 50%, in patients with <6 months and 6 months of previous immune checkpoint inhibitor (CPI) treatment, and in patients with squamous and non-squamous histology. Adverse events were consistent with the safety profiles of the individual drugs and treatment related adverse events (TRAEs) were primarily grade 1 and 2. The most common TRAEs (all grades) in Arm A were asthenia (22.7%), diarrhea (18.2%), nausea (18.2%), anemia (13.6%) and liver-related events (13.6%).

In combination arms (Arms B and C) the most common TRAEs were liver-related events (28.6%, 18.4%), fatigue (21.4%, 8.2%), asthenia (12%, 12.2%), and diarrhea (12%, 10.2%). Overall, a lower incidence of grade 3 TRAEs, treatment-related liver-related events, and lower discontinuation rates were observed with the combination therapy administered every six weeks. Transaminase elevations were generally asymptomatic and manageable with steroids and/or treatment delay and resolved more rapidly in patients treated with the combination therapy administered every six weeks.