Boehringer Ingelheim and Zai Lab launch a Phase Ib/II study combining obrixtamig and zocilurtatug pelitecan, advancing a dual DLL3-targeting strategy in SCLC and NECs.
Written By: Karthik Teja Macharla, PharmD
Reviewed By: Pharmacally Editorial Team
Boehringer Ingelheim and Zai Lab have entered a clinical collaboration to evaluate a dual DLL3‑targeting strategy in hard‑to‑treat cancers. The planned Phase Ib/II study will assess the safety, tolerability, and early clinical activity of combining obrixtamig, a DLL3/CD3 T‑cell engager, with zocilurtatug pelitecan, a DLL3‑targeting antibody–drug conjugate (ADC). The trial will enroll patients with poorly differentiated neuroendocrine carcinomas (NECs) and extensive‑stage small cell lung cancer (ES‑SCLC), where treatment options remain limited and new targeted approaches are urgently needed.
Strategic rationale behind the dual DLL3 approach
The collaboration brings together two complementary mechanisms targeting DLL3‑expressing tumors. Obrixtamig is designed to redirect T cells to attack cancer cells, while zocilurtatug pelitecan delivers a cytotoxic payload directly into those same DLL3‑positive tumor cells. This dual approach aims to enhance antitumor activity by combining immune‑mediated killing with targeted cytotoxicity.
According to Itziar Canamasas, Ph.D., Global Head of Oncology at Boehringer Ingelheim, the strategy aligns with the company’s immuno‑oncology focus on advancing targeted combinations for difficult‑to‑treat cancers and expanding options for patients with DLL3‑expressing tumors.
Rafael G. Amado, M.D., President and Head of Global Research and Development at Zai Lab, noted that zocilurtatug pelitecan (zoci) has shown encouraging activity and tolerability in SCLC and that the collaboration enables exploration of combination strategies to address unmet needs in SCLC and NECs.
Clinical progress of obrixtamig
Obrixtamig is an investigational bispecific T‑cell engager targeting DLL3 and CD3. In the global Phase I DAREON®‑8 study in first‑line ES‑SCLC, the drug, when combined with chemotherapy and atezolizumab, showed early, encouraging clinical activity with a manageable safety profile. The program is advancing into a global Phase III trial, DAREON®‑Lung‑1. Obrixtamig has received Fast Track and Orphan Drug designations from the U.S. Food and Drug Administration, as well as orphan designation from the European Commission, for the treatment of neuroendocrine carcinomas.
Advancement of zocilurtatug pelitecan
Zocilurtatug pelitecan (zoci) is an ADC engineered to selectively deliver cytotoxic therapy to DLL3‑positive tumor cells. In global Phase I studies in previously treated ES‑SCLC, the drug demonstrated durable responses, including in patients with brain metastases, along with a favorable safety profile. Based on these results, the program has progressed into a global Phase III registrational study and is also being evaluated in NECs. Zoci has received both Fast Track and Orphan Drug designations from the FDA for small cell lung cancer.
Operational framework of the collaboration
Under the agreement, Zai Lab will supply zocilurtatug pelitecan for the Phase Ib/II combination study, while Boehringer Ingelheim will lead and manage clinical operations. Each company will retain rights to its respective asset, reflecting a collaborative but asset‑independent development strategy aimed at accelerating the evaluation of this dual DLL3‑targeting regimen in patients with DLL3‑expressing ES‑SCLC and NECs.
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About the Writer
Karthik Teja Macharla, PharmD is a Pharm.D. graduate with a strong interest in clinical research, pharmacovigilance, and medical writing. In his words, he is passionate about converting complex medical information into clear, evidence-based scientific communication, committed to contributing to patient safety and advancing healthcare through accurate and impactful medical content.
