Abstract LB260: Potential prognostic/predictive biomarkers for sacituzumab govitecan in EVOKE-01

Abstract Introduction: Trophoblast cell-surface antigen 2 (Trop-2) has become an attractive antibody drug conjugate (ADC) target as it is expressed in multiple solid tumors. Sacituzumab govitecan (SG), an ADC composed of a Trop-2 antibody coupled to SN-38 by a hydrolysable linker, has demonstrated activity and is approved in metastatic triple-negative breast cancer and in metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer. EVOKE-01 (NCT05089734) evaluated the efficacy and safety of SG vs docetaxel in patients with metastatic non-small cell lung cancer (NSCLC) after receiving platinum chemotherapy and anti-PD-(L)1 treatment. The study did not meet statistical significance for the primary endpoint of overall survival (OS) at final analysis; numerical improvement in OS was seen with SG vs docetaxel. To date, the biomarkers associated with the clinical efficacy of SG in NSCLC are not well characterized. We performed a retrospective analysis of exploratory biomarkers to evaluate their predictive/prognostic value. Methods: Exploratory biomarker analyses were conducted in the biomarker evaluable population (BEP; N=380), representing 63% of the intent-to-treat (ITT) population with biomarker data available. Trop-2 protein expression was assessed using the EPR20043 FLA IHC assay (Roche-Tissue Diagnostics) and scored by a pathologist based on H-scores. The clinical data used for biomarker analyses were from the study’s final analysis (cutoff date: 29NOV2023). Results: Baseline characteristics were comparable between BEP and ITT; similar to the ITT population, there was no statistically significant difference between treatments. Trop-2 protein was highly expressed in NSCLC tumor samples, consistent with previous observations. Trop-2 expression was similar in both treatment arms with a median H-score of 190 and was slightly higher in squamous vs non-squamous NSCLC. Trop-2 expression was also similar among subgroups of patients with different best responses (SD/PD vs CR/PR) to last prior anti-PD-(L)1 therapy. Analysis of Trop-2 correlation with clinical outcomes showed that higher Trop-2 expression did not predict better OS with SG vs docetaxel; median OS hazard ratios (95% CI) with SG vs docetaxel were 0.89 (0.60-1.32) and 0.96 (0.68-1.38) in the <190 and ≥190 Trop-2 H-score subgroups, respectively. Median OS was shorter in ≥190 vs <190 Trop-2 H-score subgroups with both SG (8.90 vs 11.79 mo) and docetaxel (9.76 vs 10.71 mo). Results were consistent in squamous and non-squamous subgroups. Conclusion: Exploratory biomarker analyses were conducted to identify potential biomarkers that are either predictive for SG or prognostic for NSCLC. Trop-2 was highly expressed in NSCLC, albeit not predictive of better OS with SG compared with docetaxel. Trop-2 may be a negative prognostic biomarker in this NSCLC population, independent of treatment received in the study. Citation Format: Marina Chiara Garassino, Peiwen Kuo, Niels Reinmuth, Nicolas Girard, Giannis Mountzios, Mariano Provencio, Yvonne Summers, Marcello Tiseo, Shan Tang, Riddhi Patel, Sabeen Mekan, Juliane M. Jürgensmeier. Potential prognostic/predictive biomarkers for sacituzumab govitecan in EVOKE-01 [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_2):Abstract nr LB260.