Tumor Growth Inhibition-Overall Survival Modeling in Non-Small Cell Lung Cancer: A Case Study from GEMSTONE-302.

Overall survival is vital for approving new anticancer drugs but is often impractical for early-phase studies. The tumor growth inhibition-overall survival (TGI-OS) model could bridge the gap between early- and late-stage development. This study aimed to identify an appropriate TGI-OS model for non-small cell lung cancer (NSCLC) patients from the GEMSTONE-302 study of sugemalimab. We employed three TGI models to delineate tumor trajectories and investigated three OS model for linking TGI metric to overall survival. All three TGI models accurately captured tumor profiles at individual level. The published atezolizumab-based TGI-OS model predicted survival time satisfactorily through simulation-based evaluation, whereas the other published model built from multi-treatment underestimated overall survival. Our study-specific TGI-OS model identified time-to-growth as the most significant metric with number of metastatic sites and neutrophilto-lymphocyte ratio at baseline as covariates and exhibited robust OS predictability. Our findings demonstrated the effectiveness of the TGI-OS models in predicting phase III outcomes, which underpins their value as a powerful tool for anti-tumor drug development.