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Biomarker analysis from a Phase 1/1b study of tusamitamab ravtansine in patients with advanced non-small cell lung cancer

IF 5 2区医学 Q2 Medicine

Translational Oncology Pub Date : 2026-01-01 Epub Date: 2025-12-03 DOI:10.1016/j.tranon.2025.102615

Anas Gazzah , Nils Ternès , Joon Sang Lee , Emma Wang , Dimitri Carene , Hong Wang , Nina Masson , Eric Boitier , Aude Lartigau , Nathalie Mace , Mustapha Chadjaa , Colette Dib , Manoel Nunes , Gaëlle Muzard , Sandrine Longuemaux-Valence , Anne-Laure Bauchet

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引用次数: 0

Abstract

Background

Tusamitamab ravtansine demonstrated antitumor activity in the Phase 1/1b study of advanced non-squamous non-small cell lung cancer with high (HE, ≥2+ intensity in ≥50 % of tumor cells) or moderate (ME, ≥2+ intensity in ≥1 % to <50 % of tumor cells) carcinoembryonic antigen-related cell adhesion molecule 5 (CEACAM5) expression. Tumor CEACAM5 expression, biomarker associations and whether biomarkers predict objective response rate (ORR) were explored.

Methods

We assessed CEACAM5, circulating CEACAM5 (cCEACAM5) and CEA (cCEA). Enrollment was according to immunohistochemistry (IHC) CEACAM5 membrane expression: HE (n=64) and ME (n=28). Patients received tusamitamab ravtansine 100 mg/m² intravenously every 2 weeks.

Results

cCEA and cCEACAM5 were strongly associated (Spearman ρ, 0.99), with moderate associations between IHC CEACAM5 and cCEA or cCEACAM5 (Spearman ρ, 0.43 and 0.38). In patients with baseline cCEA data, 40.3 % (25/62) of HE and 25 % (7/28) of ME had cCEA ≥100 µg/L (median: 71.6 µg/L [1–8809] versus 12.4 µg/L [0.5–684]). Among response-evaluable patients in HE, ORR for high cCEA (≥100 µg/L) was 41.7 % (10/24) versus 8.1 % (3/37) for low cCEA, and in ME, ORR was 0/7 versus 10 % (2/20). Elevated CEACAM5 mRNA was observed in HE versus ME (P = 0.0027). EGFR and KRAS alterations were present in 44.8 % and 65.5 % of HE and in 21.4 % and 78.6 % of ME patients, respectively.

Conclusions

In CEACAM5 HE, the ORR was greater with high versus low cCEA. Associations were observed between cCEA and cCEACAM5; IHC CEACAM5, cCEA, and cCEACAM5; IHC CEACAM5 and CEACAM5 mRNA, but not between IHC CEACAM5 and oncogenic drivers.

Clinical Trial Registration: NCT02187848

查看原文本刊更多论文

tusamitamab ravtansine在晚期非小细胞肺癌患者中的1/1b期研究的生物标志物分析。

背景：Tusamitamab ravtansine在晚期非鳞状非小细胞肺癌的1/1b期研究中显示出高（HE，≥50%肿瘤细胞≥2+强度）或中等（ME，≥1%肿瘤细胞≥2+强度）的抗肿瘤活性。方法：我们评估了CEACAM5、循环CEACAM5 （cCEACAM5）和CEA （cCEA）。根据免疫组化（IHC） CEACAM5膜表达入组：HE （n=64）和ME （n=28）。患者静脉注射tusamitamab ravtansine 100mg /m2，每2周一次。结果：cCEA与cCEACAM5呈正相关（Spearman ρ, 0.99）， IHC CEACAM5与cCEA或cCEACAM5呈正相关（Spearman ρ， 0.43和0.38）。在基线cCEA数据的患者中，40.3%（25/62）的HE和25%（7/28）的ME的cCEA≥100µg/L（中位数：71.6µg/L [1-8809] vs 12.4µg/L[0.5-684]）。在HE组反应可评估的患者中，高cCEA（≥100µg/L）的ORR为41.7%(10/24)，而低cCEA的ORR为8.1%(3/37)，在ME组，ORR为0/7，而10%（2/20）。HE组与ME组CEACAM5 mRNA升高（P = 0.0027）。EGFR和KRAS的改变在HE患者中分别为44.8%和65.5%，在ME患者中分别为21.4%和78.6%。结论：在CEACAM5 HE中，高cCEA比低cCEA的ORR更大。cCEA与cCEACAM5存在相关性；IHC CEACAM5、cCEA和cCEACAM5；IHC CEACAM5和CEACAM5 mRNA，但在IHC CEACAM5和致癌驱动因子之间不存在差异。临床试验注册：NCT02187848。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Translational Oncology

Translational Oncology ONCOLOGY-

CiteScore

8.40

自引率

2.00%

发文量

314

审稿时长

54 days

期刊介绍： Translational Oncology publishes the results of novel research investigations which bridge the laboratory and clinical settings including risk assessment, cellular and molecular characterization, prevention, detection, diagnosis and treatment of human cancers with the overall goal of improving the clinical care of oncology patients. Translational Oncology will publish laboratory studies of novel therapeutic interventions as well as clinical trials which evaluate new treatment paradigms for cancer. Peer reviewed manuscript types include Original Reports, Reviews and Editorials.

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