Zai Lab Limited and Boehringer Ingelheim have entered into a new clinical collaboration to develop a dual DLL3‑targeting combination for small cell lung cancer (SCLC) and other neuroendocrine carcinomas (NECs). The partnership pairs Boehringer’s investigational DLL3/CD3 T‑cell engager obrixtamig with Zai Lab’s DLL3‑targeting antibody‑drug conjugate (ADC) zoci, formerly known as ZL‑1310.
The collaboration will launch a Phase Ib/II study designed to evaluate the safety, tolerability and initial clinical activity of the combination in patients with poorly differentiated NECs and extensive‑stage SCLC. While the exact enrollment start date has not been disclosed, the study will be conducted under Boehringer’s sponsorship of day‑to‑day clinical operations, with Zai Lab supplying the ADC. Each company retains rights to its own technology, allowing them to pursue independent development pathways if desired.
Zai Lab’s zoci has received FDA Orphan Drug Designation and Fast Track Designation for SCLC and has shown encouraging activity and a favorable safety profile in early studies. Boehringer’s obrixtamig has been evaluated in combination with chemotherapy and atezolizumab in a Phase I study and is advancing into a global Phase III trial. The dual‑targeting strategy is intended to enhance tumor cell killing by combining the immune‑engaging T‑cell engager with the cytotoxic payload delivery of the ADC, potentially improving outcomes for patients with DLL3‑expressing cancers.
"Zoci has shown encouraging activity and good tolerability in SCLC. We have rapidly advanced zoci into pivotal stage and are pursuing opportunities to explore multiple combination approaches in SCLC and other NECs. This collaboration with Boehringer Ingelheim offers a compelling DLL3‑targeting strategy with the potential to benefit patients who urgently need better treatments," said Rafael G. Amado, M.D., President and Head of Global Research and Development at Zai Lab.
"The strategy to engage the immune system with a specific T‑cell engager and deliver a potent cytotoxic payload with a DLL3‑targeting ADC, aligns with our immuno‑oncology strategy and our drive to advance smart combinations for hard‑to‑treat cancers. It's another step in our mission to expand effective options for people with DLL3‑expressing cancers," said Itziar Canamasas, Ph.D., Global Head of Oncology at Boehringer Ingelheim.
The collaboration expands Zai Lab’s global oncology pipeline and positions the company to pursue a potentially transformative therapy for a high‑need patient population. For Boehringer, the partnership provides access to a promising ADC that has demonstrated a favorable safety profile, complementing its DLL3/CD3 platform and reinforcing its commitment to innovative combination approaches in oncology.
The dual‑targeting approach could offer a competitive advantage in a field where previous DLL3‑targeted therapies, such as Rovalpituzumab tesirine, faced limited efficacy in Phase III trials. By combining a T‑cell engager with an ADC, the partnership aims to overcome resistance mechanisms and enhance immune responses, potentially improving clinical outcomes for patients with DLL3‑expressing cancers.
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