ZL-1222 (PD-1/IL-12)

Overview

ZL-1222 is an internally developed, next-generation investigational immunocytokine bispecific protein that Zai Lab is investigating for the treatment of tumors that typically elicit only a limited immune response, also known as cold tumors. It has a novel design that enables selective targeting of PD-1⁺ tumor-infiltrating lymphocytes and delivers interleukin-12 (IL-12) directly to the tumor microenvironment (TME). Through this mechanism, ZL-1222 drives a robust T cell- and natural killer (NK) cell-mediated antitumor response while minimizing systemic exposure. 

In preclinical studies, ZL-1222 demonstrated potent and durable antitumor activity in PD-1-insensitive tumor models and was well tolerated in a pilot toxicology study.  ZL-1222 is currently in preclinical development, and Zai Lab expects to complete Investigational New Drug (IND)-enabling studies in 2026.