Genmab A S and BioNTech SE announced initial data from the ongoing Phase 2 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 PD-L(1)-positive metastatic non-small cell lung cancer (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 the 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 held in Chicago, IL from 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 OS was evaluated in all centrally confirmed PD-L1-positive patients (n 80).

Arm A showed a mOS rate of 5.5 months, a 50% disease control rate (DCR) and a 31% ORR (confirmed ORR 13%) in patients treated with acasunlimab alone. An 8.6 months mOS, a 59% DCR and a 21% ORR (confirmed ORR 18%) for treatment of acasunlimab in combination with pembrolizumab every three weeks (Arm B) and a 17.5 months mOS, a 75% DCR and a 30% ORR (confirmed ORR 17%) when the combination was administered every six weeks (Arm C). Anti-tumor activity was observed in patients with a 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 the 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 regimen therapy administered every six weeks.

Transaminase elevations, were generally asymptomatic and manageable with the administration of steroids and or treatment delay and resolved more rapidly in patients treated with the combination therapy administered every six weeks. The GCT1046-04 trial (NCT05117242) is a randomized, open-label trial evaluating the safety and efficacy of acasunlimab in patients with relapsed refractory metastatic non-small cell lung cancer (mNSCLC") after treatment with standard of care therapy containing immune checkpoint inhibitor therapy. Patients with stage IV NSCLC with at least one prior line of systemic therapy containing an anti-PD-1 PD-L1 and a tumor PD-L1 expression in 1% of the tumor cells are included in the study.

The primary endpoint of the trial is the overall response rate (ORR"). Key secondary endpoints include overall survival (OS"), progression free survival (PFS"), time to response (TTR"), duration of response (DOR"), and safety. More information on this trial can be found at

Non-small cell lung cancer (NSCLC") is the most common type of lung cancer, accounting for about 85% of all reported cases. NSCLC starts in cells that line the airways and can grow into nearby tissues or spread to other parts of the body. NSCLC is often diagnosed at an advanced stage, when it is hard to treat and has a poor prognosis.

The survival rate of patients with NSCLC varies depending on the stage at diagnosis.i,ii,iii,The treatment of NSCLC depends on the stage, subtype, and biomarker status of the disease, and may include surgery, radiation therapy, chemotherapy, targeted therapy, immunotherapy, or a combination of these modalities.