Boehringer Ingelheim and China-based Zai Lab (NASDAQ: ZLAB; HKEX: 9688; Shanghai/Cambridge, Mass.) announced a clinical collaboration to evaluate a dual DLL3-targeting cancer combination in extensive-stage small cell lung cancer (ES-SCLC) and neuroendocrine carcinomas (NECs). The arrangement brings together obrixtamig, Boehringer Ingelheim’s DLL3/CD3 bispecific T-cell engager, and zocilurtatug pelitecan (zoci; formerly ZL-1310), Zai Lab’s DLL3-targeted antibody-drug conjugate (ADC), in a Phase Ib/II combination study assessing safety, tolerability, and initial clinical activity. Financial terms were not disclosed.
Both obrixtamig and zocilurtatug pelitecan target DLL3, a Notch ligand paralog aberrantly expressed on neuroendocrine tumor cells with limited expression in normal tissue. Obrixtamig redirects cytotoxic T-cells to DLL3-expressing tumor cells by bridging CD3 on T-cells with DLL3 on the tumor surface. Zocilurtatug pelitecan delivers a pelitecan payload — a camptothecin-derived topoisomerase I inhibitor — directly to DLL3-expressing cells via an anti-DLL3 antibody.This approach seeks to leverage immunogenic cell death: the ADC’s chemotoxic payload may sensitize the tumor microenvironment, potentially enhancing the efficacy of the T-cell engager. The Phase Ib/II study will enroll patients with ES-SCLC and poorly differentiated NECs, indications where available treatment options remain limited.
The collaboration is Zai Lab’s second in quick succession assessing dual targeting of DLL3. Last month, Zai announced a similar clinical trial collaboration with Amgen to pair zoci with the US firm’s DLL3-tatgeted bispecific T-cell engager Imdelltra (tarlatamab-dlle).