Evaluation of Biomarkers for Sacituzumab Govitecan in Metastatic Non-Small Cell Lung Cancer: Insights From the EVOKE-01 Study

Introduction: This exploratory analysis assessed predictive biomarkers for sacituzumab govitecan (SG) in the open-label, phase III EVOKE-01 study of SG versus docetaxel in non–small cell lung cancer (NSCLC). Methods: Trophoblast cell surface antigen (Trop)-2 membrane protein expression was analyzed using immunohistochemistry in the Trop-2 biomarker evaluable population (BEP). Circulating tumor DNA (ctDNA) analyses evaluated baseline and reduction of ctDNA with treatment and identified oncogenic driver alterations (KRAS, TP53, KEAP1, and STK11) and other relevant mutations in the ctDNA BEP. Results: Median overall survival (OS) with SG versus docetaxel was 8.9 versus 9.8 months (hazard ratio [HR] = 0.96, 95% CI: 0.68-1.38) and 11.8 versus 10.7 months (HR = 0.89, 95% CI: 0.60-1.32) in subgroups with Trop-2 histological scores greater than or equal to the median and less than the median, respectively. As expected, median OS was longest in patients with undetectable baseline ctDNA. ctDNA reduction was observed after the first cycle with either treatment. KRAS driver alterations and potential immunotherapy resistance mutations (TP53, KEAP1, and STK11) were negative prognostic factors. Patients with TP53 mutations derived more benefit from SG than docetaxel. SG activity was observed independent of DNA damage repair mutations. Conclusion: Trop-2 expression did not identify patients benefiting more from SG than from docetaxel. ctDNA reduction supported SG as active therapy in NSCLC. Evaluation of clinically relevant biomarkers in NSCLC identified KRAS, TP53, STK11, and KEAP1 mutations as negative prognostic factors in these second-line–treated patients.