China-based Simcere Pharmaceutical Group (HKG: 2096) has announced the first patient in (FPI) a clinical study for its bispecific antibody (BsAb) SIM0237, targeting PD-L1 and IL-15 in advanced solid tumors. The global multi-center, open-label Phase I study is designed to assess the safety, efficacy, and pharmacokinetics/pharmacodynamics of the drug. The study is expected to enroll 192 cases and will commence simultaneously in China and the United States.
Mechanism of Action
SIM0237 is a PD-L1 monoclonal antibody (mAb) and inactivated IL-15/IL-15R α sushi fusion protein. It blocks the PD-1/PD-L1 immunosuppressive pathway by binding to PD-L1 and activates the immune system through IL-15, providing a synergistic effect of relieving immunosuppression and activating immune anti-tumor pathways. The inactivated IL-15 terminal of SIM0237 increases drug exposure and avoids over-activation and depletion of NK and CD8+ T cells.
Advantages and Delivery
The fusion of inactivated IL-15 and PD-L1 antibodies extends the half-life of IL-15 and delivers IL-15 directly to the tumor microenvironment, reducing systemic exposure and toxicity. Additionally, inactivated IL-15 matches the dose of PD-L1 to maximize the efficacy of PD-L1 antibodies. SIM0237 bridges CD8+ T cells, NK cells, and PD-L1+ antigen-presenting cells, promoting the formation of immune synapses and enhancing the activation of effector cells to kill tumor cells.
Pre-Clinical Findings
Pre-clinical studies have shown that SIM0237 demonstrates better efficacy than PD-L1 and IL-15 alone in mouse tumor models. This highlights the potential of SIM0237 to offer a more effective treatment option for patients with advanced solid tumors.
Significance of the Clinical Trial
The initiation of the Phase I clinical trial for SIM0237 marks a significant step in the development of this innovative bispecific antibody. It underscores Simcere Pharmaceutical’s commitment to advancing novel therapies that can improve patient outcomes in cancer treatment.-Fineline Info & Tech
