Phase 2 Trial: Acasunlimab and Pembrolizumab Show Activity in Treated Metastatic NSCLC

COPENHAGEN, Denmark, and MAINZ, Germany; June 1, 2024 — Genmab A/S and BioNTech SE have shared promising initial data from the ongoing Phase 2 GCT1046-04 clinical trial (NCT05117242), which evaluates the investigational bispecific antibody acasunlimab (DuoBody-PD-L1x4-1BB), also identified as GEN1046/BNT311. Preliminarily, the combination therapy with pembrolizumab has shown notable efficacy in patients with previously treated PD-L1-positive metastatic non-small cell lung cancer (mNSCLC).

The study revealed a 12-month overall survival (OS) rate of 69% and a median overall survival (mOS) of 17.5 months, with a 30% overall response rate (ORR) and a confirmed ORR of 17% for patients receiving the combination therapy every six weeks. These findings were recently presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting.

The Phase 2 trial involved 113 patients randomized into three arms to assess acasunlimab alone (Arm A) and in combination with pembrolizumab (Arms B and C). Detailed evaluations were conducted on 62 patients with centrally confirmed PD-L1-positive tumors. In terms of overall survival, Arm A exhibited an mOS of 5.5 months with a 50% disease control rate (DCR) and a 31% ORR (confirmed ORR 13%). For Arm B, which used the combination therapy every three weeks, the mOS was 8.6 months with a 59% DCR and a 21% ORR (confirmed ORR 18%). Arm C, administering the combination every six weeks, showed the most promising results with a 17.5 month mOS, a 75% DCR, and a 30% ORR (confirmed ORR 17%).

The treatment showed anti-tumor activity across various patient subgroups, including different tumor proportion scores (TPS) and durations of prior immune checkpoint inhibitor treatments, as well as diverse histologies (squamous and non-squamous).

Safety profiles were consistent with known characteristics of the individual drugs. Most treatment-related adverse events (TRAEs) were grades 1 and 2. Common TRAEs in Arm A included asthenia (22.7%), diarrhea (18.2%), nausea (18.2%), anemia (13.6%), and liver-related events (13.6%). In contrast, combination arms (Arms B and C) reported liver-related events (28.6%, 18.4%), fatigue (21.4%, 8.2%), asthenia (12%, 12.2%), and diarrhea (12%, 10.2%). Combination therapy administered every six weeks showed fewer high-grade TRAEs and liver-related events, alongside lower discontinuation rates. Notably, transaminase elevations were usually asymptomatic and managed effectively with steroids or treatment delays, resolving quicker in patients receiving six-week interval therapy.

Judith Klimovsky, Executive Vice President & Chief Development Officer at Genmab, remarked on the encouraging findings, highlighting the potential impact on mNSCLC patients. She emphasized ongoing evaluations to inform future developments, including a planned Phase 3 trial.

Prof. Özlem Türeci, M.D., Chief Medical Officer and Co-Founder of BioNTech, noted the limited options for mNSCLC patients post progression on initial checkpoint inhibitor therapy. She pointed out the data's significance, suggesting that combining acasunlimab with PD-L1 blockade could offer a valuable treatment approach for this heavily pre-treated patient group.

The GCT1046-04 study is a randomized, open-label trial focusing on the safety and efficacy of acasunlimab in relapsed/refractory mNSCLC patients who have undergone at least one prior line of systemic therapy including an anti-PD-1/PD-L1 treatment. The primary endpoint is the overall response rate (ORR), with secondary endpoints including overall survival (OS), progression-free survival (PFS), time to response (TTR), duration of response (DOR), and safety.

Non-small cell lung cancer (NSCLC), representing about 85% of lung cancer cases, is often diagnosed at advanced stages, posing treatment challenges and poor prognosis. Treatment strategies vary based on the stage, subtype, and biomarkers, typically involving surgery, radiation, chemotherapy, targeted therapy, immunotherapy, or their combinations.

Acasunlimab, developed collaboratively by Genmab and BioNTech, uses bispecific antibody technology to activate T cells and natural killer (NK) cells conditionally, upon simultaneous binding to PD-L1. This agent’s development is part of ongoing efforts to provide effective and innovative treatments for advanced cancers.

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