Iza-bren + serplulimab as first line treatment for extensive stage small cell lung cancer

Iza-bren is a potential first-in-class bispecific antibody drug conjugate (ADC) consisting of an EGFR x HER3 bispecific antibody linked to a topoisomerase I inhibitor payload. This agent is currently under evaluation across multiple lung cancer settings, with promising data in heavily pretreated EGFR-mutated NSCLC patients being published in Annals of Oncology earlier this year.¹ During the 2026 European Lung Cancer Conference (ELCC), new results with this agent were presented in extensive-stage small cell lung cancer (ES-SCLC), a disease with limited therapeutic innovation in the first-line setting.

The study explored two dose levels (2.5 or 2.75 d1 & d8 q3w) within a dose-optimization framework and included both pre-treated and treatment-naïve patients. Notably, in the first-line setting, iza-bren was combined with serplulimab, an anti–PD-1 immune checkpoint inhibitor. For Prof Mariana Brandão (Institut Jules Bordet, Brussels), pursuing such a chemotherapy-free strategy in ES-SCLC is a bold move given the established role of platinum-based chemotherapy in the first-line treatment of this disease.

Efficacy outcomes were encouraging, with reported objective response rates ranging from 85% to 92% and a median progression-free survival of approximately 8 months. The safety profile was consistent with expectations for ADCs, with predominantly hematologic toxicities. Importantly, the incidence of pneumonitis, a known concern with some ADCs such as trastuzumab deruxtecan, was low, providing reassurance regarding pulmonary safety. Based on these findings, the lower dose (2.5) was selected for further development. 

A phase III trial is planned, comparing iza-bren in combination with anti–PD-1 therapy vs. the current standard of care consisting of platinum-based chemotherapy plus immunotherapy (i.e., the CASPIAN regimen). However, the evolving treatment landscape may complicate the interpretation of future study results. In fact, ongoing trials such as DeLLphi-303 are investigating T-cell engagers (e.g., tarlatamab) in combination with immunotherapy, which may redefine first-line standards. Consequently, the positioning of ADC-based regimens will depend on comparative efficacy against these emerging approaches. Overall, however, iza-bren represents a promising addition to the therapeutic arsenal in ES-SCLC, warranting further investigation in randomized controlled trials.