PO.CT01.02 · 临床试验

TAVO412（一种抗EGFR/cMET/VEGF多特异性抗体）治疗晚期或转移性实体瘤患者的初步临床结果

Preliminary clinical results of TAVO412, an anti-EGFR/cMET/VEGF multispecific antibody, in patients with advanced or metastatic solid tumors

编号 CT050 展板 10 时间 4/20 09:00–12:00 区域 Section 50 主讲 Mark Chiu, PhD

分会场 First-in-Human Phase I Clinical Trials

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Mark Chiu¹, Yanjiao Yu¹, Mira Zhao², Wei Zhang², Hong Xie³, Chao Han¹

¹Tavotek Lab Inc., Lower Gwynedd, PA,²Tavotek Lab Inc., Suzhou, China,³HX Consulting, Spring House, PA

摘要 Abstract

中文摘要

背景：TAVO412具有两个抗EGFR纳米抗体样结构域、一个抗cMET Fab臂和一个抗VEGF单链可变片段，并具有增强的Fc效应功能。其设计利用亲合力抑制EGFR配体结合和受体异源二聚化、关闭cMET信号，并在EGFR/cMET高表达的肿瘤微环境中螯合可溶性VEGF-A。TAVO412在多种实体瘤细胞系来源和NSCLC患者样本来源的异种移植模型中显示出强大的抗肿瘤活性，支持其临床评价。方法：TAVO412-CN001（NCT06761651）是一项两部分、开放标签的I期研究，评估TAVO412在对标准疗法难治的晚期或转移性实体瘤患者中的安全性、耐受性和初步抗肿瘤活性。此处我们报告A部分的初步结果，该部分采用标准3+3设计进行剂量递增至1500 mg，并在相关队列中回填以进一步评估安全性和初步疗效1,2,3。结果：截至2025年12月30日，67例患者（6种肿瘤类型：NSCLC n=33、ESCC n=13、CRC n=18，以及肝癌、胃癌和乳腺癌各n=1）在A部分的5个剂量队列中入组，剂量从150至1500 mg，每2周一次（q2w）。9例患者仍在治疗中。血清药物暴露量随剂量以靶点介导的药物处置方式增加。TAVO412免疫原性低（6%）。未报告DLT，未达到MTD。所有剂量下最常见的治疗中出现的（TE）AE（≥30%）为皮疹、低白蛋白血症、口腔炎、输注相关反应、ALT升高和低钾血症。在375至1500 mg剂量范围内，在可评估疗效的NSCLC患者（n=27）中观察到初步疗效信号，5例PR（9例EGFR Exon20ins中3例，12例Exon21 L858R中2例）和13例SD；在ESCC（n=11）中1例PR和8例SD；在CRC（n=15）中4例PR和9例SD。大多数PR为确证。最长治疗持续时间约为38周。基线血清可溶性游离VEGF-A水平与缓解相关。结论：TAVO412在剂量高达1500 mg时耐受良好，安全性可控。在经过大量既往治疗的CRC、ESCC和NSCLC患者中观察到TAVO412的初步活性。有理由在这些肿瘤类型的患者中进一步评价TAVO412。关键词：多特异性抗体；EGFR；cMET；VEGF-A；非小细胞肺癌（NSCLC）；食管鳞状细胞癌（ESCC）；结直肠癌（CRC）伦理批准：本研究经CRADL-苏州伦理委员会（P202302160002）、NMPA IND（2023LP01660）和河南省肿瘤医院伦理委员会（2023-314-003）批准。参考文献。1Front Oncol. (2025) 15:1533059. doi: 10.3389/fonc.2025.1533059. eCollection 2025. 2Cancer Res (2025) 85 (8_Supp_2): CT185. doi.org/10.1158/1538-7445.AM2025-CT185 3Front. Immunol. Sec. Cancer Immunity and Immunotherapy (2025) Vol 16 doi.org/10.3389/fimmu.2025.1505868

查看英文原文 English abstract

Background: TAVO412 has two anti-EGFR nanobody-like domains, an anti-cMET Fab arm, and an anti-VEGF single-chain variable fragment, with enhanced Fc effector functions. It is designed to use avidity to inhibit EGFR ligand binding and receptor heterodimerization, shut down cMET signaling, and sequester soluble VEGF-A in the EGFR/cMET-high tumor microenvironments. TAVO412 has demonstrated robust antitumor activities in multiple solid tumor cell line-derived and NSCLC patient sample-derived xenograft models, supporting its clinical evaluation. Methods: TAVO412-CN001 (NCT06761651) is a two-part, open-label Phase I study evaluating the safety, tolerability, and preliminary antitumor activity of TAVO412 in patients with advanced or metastatic solid tumors refractory to standard therapies. Here we report the preliminary results from Part A that uses a standard 3+3 design for dose-escalation up to 1500 mg, with backfill in relevant cohorts to further assess safety and preliminary efficacy 1,2.3 . Results: As of Dec. 30, 2025, 67 patients, with 6 tumor types (NSCLC n=33, ESCC n=13, CRC n=18, and n=1 each in liver, gastric and breast cancer), were enrolled in 5 dose cohorts from 150 to 1500 mg, q2w, in Part A. Nine patients still remain on the treatment. Serum drug exposures increased with the dose in a target mediated drug-disposition manner. TAVO412 had low immunogenicity (6%). No DLTs were reported and the MTD had not been reached. The most common treatment-emergent (TE) AEs (≥30%) across all doses were rash, hypoalbuminemia, stomatitis, infusion related reaction, increase ALT, and hypokalemia. Preliminary efficacy signals were observed in efficacy-evaluable NSCLC patients (n=27) with 5 PRs (3 of 9 EGFR Exon20ins and 2 of 12 Exon21 L858R) and 13 SDs, in ESCC (n=11) with 1 PR and 8 SDs, and in CRC (n=15) with 4 PRs and 9 SDs, in the dose range from 375 to 1500 mg. Most PRs were confirmed. The longest treatment duration was approximately 38 weeks. The baseline serum soluble free VEGF A levels correlated with the responses. Conclusion: TAVO412 was well tolerated up to 1500 mg with a manageable safety profile. Preliminary activities of TAVO412 have been observed in CRC, ESCC, and NSCLC patients who had been heavily pretreated. Further evaluation of TAVO412 in patients with these type of tumors is warranted. Keywords: Multispecific antibody; EGFR; cMET; VEGF-A; non-small cell lung cancers (NSCLC); esophageal squamous cell cancer (ESCC); colorectal cancer (CRC) Ethics Approval: This study was approved by the CRADL-Suzhou Ethics Board (P202302160002), NMPA IND (2023LP01660), and Henan Cancer Hospital Ethics Board (2023-314-003). References. 1Front Oncol. (2025) 15:1533059. doi: 10.3389/fonc.2025.1533059. eCollection 2025.2 Cancer Res (2025) 85 (8_Supp_2): CT185. doi.org/10.1158/1538-7445.AM2025-CT1853Front. Immunol. Sec. Cancer Immunity and Immunotherapy (2025) Vol 16 doi.org/10.3389/fimmu.2025.1505868

利益披露 Disclosure

M. Chiu, None.. Y. Yu, None.. M. Zhao, None.. W. Zhang, None.. H. Xie, None.. C. Han, None.

← 返回 AACR 2026 检索