Abstract LB399: Trop-2 expression and association with efficacy in patients treated with sacituzumab govitecan + pembrolizumab +/- carboplatin in the EVOKE-02 study of non-small cell lung cancer

Abstract Introduction: Sacituzumab govitecan (SG) is a first-in-class, trophoblast cell-surface antigen 2 (Trop-2)-directed antibody-drug conjugate with a hydrolysable linker and a potent SN-38 payload. SG is approved in metastatic triple-negative breast cancer and in metastatic hormone receptor-positive/human epidermal growth factor receptor 2-negative breast cancer and is being investigated for the treatment of metastatic non-small cell lung cancer (mNSCLC). In the ongoing, open-label, global, phase II EVOKE-02 (NCT05186974) study of mNSCLC without actionable genomic alterations (AGAs), first-line (1L) SG + pembrolizumab +/− carboplatin demonstrated encouraging efficacy, and data from an exploratory analysis of Trop-2 as a potential prognostic/predictive biomarker are presented here. Methods: The biomarker evaluable population (BEP; patients with Trop-2 data) consisted of 129 (70%) patients of the 184 in the Full Analysis Set (FAS). Archival tumor samples collected at enrollment were analyzed for Trop-2 membrane expression by histological scores (H-scores; scale 0-300) using the EPR20043 FLA IHC assay (Roche Tissue Diagnostics). Trop-2 association with clinical endpoints (objective response rate [ORR] and progression-free survival [PFS]) was evaluated using clinical data from the June 03, 2024, data cut. Results: Trop-2 was highly expressed in tumor samples with a median Trop-2 H-score of 178 (0.0, 296.0). Baseline characteristics and clinical outcomes for the BEP were comparable to the FAS. Trop-2 expression was comparable in tumors with squamous and non-squamous histology and PD-L1 (22C3; tumor proportion score [TPS] < 1%, 1-49%, ≥ 50%) subgroups. No difference in ORR or PFS between Trop-2 (H-score median cut) subgroups was observed. In patients treated with SG + pembrolizumab, ORR (95% CI) was 33.3% (18.0-51.8) for those with Trop-2 H-scores < median and 35.3% (19.7-53.5) for those with Trop-2 H-scores ≥ median, and median PFS was 6.90 months and 8.48 months, respectively (HR, 1.165 [95% CI, 0.59-2.31]). In patients treated with SG + pembrolizumab + carboplatin, ORR (95% CI) was 33% (17.3-52.8) and 44% (26.4-62.3) for patients with Trop-2 H-scores < median and ≥ median, and median PFS was 5.47 and 8.74 months, respectively (HR, 0.678 [95% CI, 0.35-1.31]), with CIs overlapping. Conclusions: Trop-2 protein was highly expressed in patients with mNSCLC without AGAs with 1L treatment in EVOKE-02. The analysis of ORR and PFS across the Trop-2 subgroups in EVOKE-02 indicates that the efficacy of SG + pembrolizumab +/− carboplatin was independent of Trop-2 expression. The 1L combination of SG + pembrolizumab in patients with PD-L1 expression ≥ 50% TPS is being evaluated in the phase III EVOKE-03 study on mNSCLC. Citation Format: Jyoti D. Patel, Marianna Zavodovskaya, Byoung Chul Cho, Martin Reck, Jhanelle E. Gray, Noemí Reguart, Enriqueta Felip, Joel W. Neal, Kai-Wen Lin, Juliane M. Jürgensmeier, Sabeen Mekan, Farnoush Safavi, Michael Chisamore, Edward Garon. Trop-2 expression and association with efficacy in patients treated with sacituzumab govitecan + pembrolizumab +/- carboplatin in the EVOKE-02 study of non-small cell lung cancer [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 LB399.