Amgen’s FDA-approved DLL3-targeting T-cell engager tarlatamab (Imdelltra) reduced the risk of death by 40% vs chemotherapy in extensive-stage small-cell lung cancer (ES-SCLC) in the Phase III DeLLphi-304 trial, supporting DLL3 as a clinically validated target in Lung Cancer. Now Boehringer Ingelheim and BioNTech are launching a Phase Ib/II study combining Boehringer’s DLL3 T-cell engager obrixtamig (BI 764532) with BioNTech/BMS’ PD-L1/VEGF bispecific pumitamig (BNT327) in ES-SCLC, with dosing expected in 2H.

Why It Matters To Oncology

• DLL3 has moved from “promising antigen” to validated survival benefit in ES-SCLC, raising the bar for next-gen DLL3 programs and combinations.

• The BI–BioNTech combo aims to pair T-cell redirection (DLL3) with microenvironment modulation (PD-L1/VEGF) to address immune evasion and angiogenesis-driven immunosuppression in SCLC.

• Early signals keep interest high: obrixtamig + chemo + atezolizumab showed a 68% ORR, 89% disease control, and 52% PFS at 9 months in Phase I DAREON 8.

The Financials

• The BI–BioNTech collaboration terms weren’t disclosed in the release.

• Deal activity underscores competitive intensity: AbbVie recently agreed to pay up to $1.2B for ex-China rights to the DLL3 TCE ZG006 (alveltamig).

• Multiple late-stage bets are in motion, including Boehringer’s Phase III DAREON-Lung-1 (planned ~670 patients) for obrixtamig + chemo + atezolizumab in advanced SCLC.

What They're Saying

• “By uniting T-cell redirection against DLL3 with PD-L1 and VEGF pathway modulation, we aim to address two central barriers in SCLC — immune evasion and an immunosuppressive, pro-angiogenic microenvironment,” Boehringer oncology lead Itziar Canamasas said.

• BioNTech’s pumitamig has posted mid-stage ES-SCLC activity signals including a 76.3% confirmed response rate, 100% disease control, and median PFS of 6.8 months in one readout (with broadly similar results reported in a separate China study).

What's Next

• Phase Ib/II obrixtamig + pumitamig will start dosing in 2H, testing whether dual immune activation + VEGF blockade can improve depth/durability of response in ES-SCLC.

• Watch for safety/tolerability details: combining a T-cell engager with PD-(L)1/VEGF biology could amplify immune toxicities and require careful step-up dosing/monitoring strategies.

• Competitive readouts will shape positioning: pumitamig is already in Phase III (ROSETTA LUNG-01) in untreated SCLC, while other PD-(L)1/VEGF programs (e.g., ivonescimab) are expanding across lung cancer settings.