Boehringer Ingelheim and BioNTech SE (Nasdaq: BNTX) announced a clinical trial collaboration and supply agreement to conduct a Phase Ib/II study evaluating a combination regimen in extensive-stage small cell lung cancer (ES-SCLC). The study will pair Boehringer Ingelheim’s obrixtamig (BI 764532), a DLL3-targeting T-cell engager, with pumitamig (BNT327/BMS-986545), a PD-L1 VEGF-A bispecific antibody being jointly developed by BioNTech and Bristol Myers Squibb (NYSE: BMY). Both companies retain full rights to their respective assets under a mutually non-exclusive structure, and no financial terms were disclosed.
The study will assess safety, tolerability, and early clinical activity of the combination in ES-SCLC, with Boehringer Ingelheim serving as regulatory sponsor. BioNTech will supply pumitamig for the trial. Patient dosing is expected to begin in the second half of 2026.
The combination targets two mechanistically distinct barriers in ES-SCLC. Obrixtamig redirects cytotoxic T-cells to DLL3-expressing tumor cells by simultaneously binding DLL3 on the tumor surface and CD3 on T-cells, forcing an immunological synapse independent of MHC-I antigen presentation. Pumitamig addresses immune checkpoint suppression and pro-angiogenic immunosuppression through concurrent PD-L1 blockade and VEGF-A neutralization in a single molecule. ES-SCLC represents approximately 15 to 20 percent of all lung cancer cases, progresses rapidly, and almost universally recurs within a year of initial treatment despite current standard-of-care regimens incorporating platinum-based chemotherapy and checkpoint inhibition.
Obrixtamig is advancing into a global Phase III trial in ES-SCLC, designated DAREON-Lung-1 (NCT07472517), and has received FDA Fast Track and Orphan Drug Designations, as well as Orphan Drug status from the European Commission for neuroendocrine carcinomas. In the Phase I DAREON-8 study evaluating obrixtamig in combination with chemotherapy and atezolizumab in first-line ES-SCLC, the agent achieved a 68% confirmed objective response rate, an 89% disease control rate, and a nine-month progression-free survival rate of 52%. Pumitamig has also advanced into a global Phase III trial, ROSETTA LUNG-01 (NCT06712355), following Phase II data in first-line ES-SCLC that showed a 76.3% confirmed objective response rate, a 100% disease control rate, and a median progression-free survival of 6.8 months in combination with chemotherapy. Pumitamig received FDA Orphan Drug Designation for SCLC in 2025.
The DLL3-targeting T-cell engager class has gained clinical validation following Amgen’s tarlatamab, which received FDA accelerated approval in May 2024 for ES-SCLC, establishing DLL3 as a clinically actionable target in this indication. Obrixtamig enters the Phase Ib/II combination study with a dataset from DAREON-8 that positions it as a competitive asset in the DLL3-targeting space.