(B-015) Harnessing Real-World Clinicogenomics for Non-Small Cell Lung Cancer Drug Development: An Initial Report

Background: Immune checkpoint inhibitors (ICIs) have significantly improved outcomes for cancer patients, but resistance remains a challenge.

Objectives: This study aims to investigate mechanisms of ICI resistance in non-small-cell lung cancer (NSCLC) using multimodal data from Tempus Inc. In 2023, a cross-functional collaboration between Global Medical Epidemiology (GME) and Computational Biology (CompBio) within Pfizer was initiated to address this challenge.

Methods: A retrospective cohort study was conducted on metastatic NSCLC patients treated with ICIs. The data encompassed patient characteristics, treatment patterns, molecular profiles, and patient outcomes such as Progression Free Survival (PFS) and Overall survival (OS). Treatment patterns were visually represented using a Sankey diagram. Kaplan-Meier analysis and plots were used to describe PFS and OS. An ongoing analysis will evaluate of clinical and molecular features as predictors of patient survival and potential tumor resistance and will be presented upon completion.

Results: We analyzed a total of 883 metastatic NSCLC patients treated with ICIs, including 500 pre-treatment and 405 post-progression tumor samples. The mean age of the patients was 65.0 years (SD=9.8), with approximately 53.2.% (n=446) being male. The majority (n=648, 73.4%) received anti-PD1 therapy in the first line treatment, either alone or in combination with other treatments. As patients advanced to the second line and third line treatments, the use of anti-PD1 therapy diminished. The median PFS and OS after the initial ICIs treatment in the metastatic setting were 5.8 months and 13.9 months, respectively.

Conclusions: The preliminary findings from this study highlight the potential of Real-World Clinicogenomics data, strengthening confidence in the Tempus dataset as a promising resource for future oncology research. Ongoing analyses aim to provide insights into potential resistance mechanisms in NSCLC patients treated with ICIs, which will inform future drug development and treatment strategies.