Abstract 6390: Exploratory biomarker analysis of phase 3 ASTRUM-005 study: Serplulimab versus placebo plus chemotherapy for extensive-stage small cell lung cancer

Abstract Background First-line serplulimab plus chemotherapy (chemo) significantly improved OS compared with chemo alone for patients with extensive-stage small cell lung cancer (ES-SCLC) in the phase 3 ASTRUM-005 study. In this exploratory biomarker analysis, we retrospectively evaluated the association of proteome signature, genetic mutations, and hematological indices with efficacy. Methods: Serum proteomics data were generated via Olink® Explore 3072 platform for 168 patients (training: 80; validation: 88). Genetic mutations were assessed by Med1CDxTM panel for 305 patients. Baseline neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lactate dehydrogenase (LDH) levels were analyzed in all 585 patients. Clinical data cutoff date was June 13, 2022. Results: From Olink data, we generated a 15-protein signature. Results in the validation cohort are shown in the table below. Patients with upper signature score derived higher PFS (7.89 vs 4.17 mo, HR 0.37) and OS (17.18 vs 9.74 mo, HR 0.27) benefit from adding serplulimab, than those with lower signature score (PFS: 4.40 vs 4.34 mo, HR 0.68; OS: 9.05 vs 9.22 mo, HR 0.76). Patients with mutations in RB1 or NOTCH pathway had better tumor responses to the treatment of serplulimab-chemo (ORR: 80% and 86%, respectively) when compared to patients without mutations in RB1 or NOTCH pathway (ORR: 58% and 68%). Patients with NLR ≤4.6, PLR ≤338.3, and LDH ≤ upper limit of normal tended to have longer PFS and OS in both treatment groups; NLR and LDH were further proven to be independent prognostic biomarkers in multivariate regression (P = 0.002 and P <0.001, respectively). Conclusions: We found a 15-protein signature showing predictive power for serplulimab-chemo treatment; RB1 or NOTCH pathway mutations were enriched in serplulimab-chemo responders; baseline NLR and LDH were independent prognostic biomarkers for ES-SCLC. The above findings warrant further investigations. Serplulimab-chemo (n=48) Placebo-chemo (n=40) HR (95% CI) P Upper signature score, n 31 34 Median PFS (95% CI), months 7.89 (1.27, 10.74) 4.17 (2.96, 4.34) 0.37 (0.21, 0.66) <0.001 Median OS (95% CI), months 17.18 (11.01, NE) 9.74 (6.90, 12.65) 0.27 (0.15, 0.50) <0.001 Lower signature score, n 17 6 Median PFS (95% CI), months 4.40 (3.61, 5.75) 4.34 (2.66, NE) 0.68 (0.23, 2.02) 0.488 Median OS (95% CI), months 9.05 (6.67, 11.73) 9.22 (4.53, NE) 0.76 (0.29, 1.98) 0.570 Citation Format: Ying Cheng, Liang Han, Lin Wu, Jun Chen, Hongmei Sun, Guilan Wen, Yinghua Ji, Anastasia Zimina, Jianhua Shi, Zhijie Pan, Jinsheng Shi, Xicheng Wang, Fang Yang, Xinyi Yang, Mengkai Chen, Shiqi Zhong, Qingyu Wang, Jing Li, Jiancheng Cheng, Chen Ling, Yongqiang Shan, Jun Zhu, The ASTRUM-005 Study Group. Exploratory biomarker analysis of phase 3 ASTRUM-005 study: Serplulimab versus placebo plus chemotherapy for extensive-stage small cell lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6390.