PO.CTP01.02 · 进行中的临床试验

一项ivonescimab用于既往接受治疗的胸腺癌的II期试验 UCLA L-11

A phase II trial of ivonescimab for previously treated thymic carcinoma UCLA L-11

编号 CT281 展板 15 时间 4/21 02:00–05:00 区域 Section 51 主讲 Jonathan Boiarsky, MD

分会场 Phase I and Phase II Clinical Trials in Progress

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作者与单位 Authors & Affiliations

Jonathan A. Boiarsky¹, Chi-hong Tseng¹, Zhaohui Arter², Matthew Gubens³, Chul Kim⁴, Jennifer A. Marks⁵, Surbhi Singhal⁶, Christine Kivork¹, Larissa Ikenouye¹, Jonathan W. Goldman¹

¹University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA,²University of California Irvine, Health Chao Family Comprehensive Cancer Center, Orange, CA,³University of California San Francisco, Hellen Diller Family Comprehensive Cancer Center, San Francisco, CA,⁴MedStar Georgetown University Hospital, Washington, DC,⁵Dana-Farber Cancer Institute, Boston, MA,⁶University of California Davis Comprehensive Cancer Center, Sacramento, CA

摘要 Abstract

中文摘要

背景：胸腺癌（TC）是一种罕见且侵袭性的胸腺上皮性肿瘤（TET），约占胸腺肿瘤的20%。TC通常较其他TET更具侵袭性且对标准治疗反应较差，在晚期/转移性阶段的5年生存率为30-50%。铂类化疗进展后有效治疗仍然有限。程序性死亡（配体）1（PD-(L)1）抑制在复发性TC中显示出中等活性，客观缓解率（ORR）为19.5-22.5%，毒性可控[Cho, Clin Oncol. 2019; Giaccone, J Thorac Oncol. 2021]。此外，用舒尼替尼或仑伐替尼进行血管上皮生长因子（VEGF）抑制在二线及以后治疗中达到26-38%的ORR（Thomas, Lancet Oncol. 2015; Sato, Lancet Oncol. 2020）。仑伐替尼联合帕博利珠单抗作为二线及以后治疗显示出22.5%的ORR，中位缓解持续时间为8.2个月（Remon, Lancet Oncol. 2025）。 Ivonescimab是一种同时靶向PD-1和VEGF的人源化双特异性单克隆抗体，在非小细胞肺癌中显示出良好的安全性和疗效。鉴于VEGF和PD-(L)1阻断在TC中的已知获益，本研究旨在评估ivonescimab在既往接受治疗的TC患者中的安全性和疗效。方法：本研究是一项多中心、开放标签、单臂II期试验，入组经组织学或细胞学确诊的不可切除/转移性TC且疾病在系统治疗后进展的成人。关键入组标准包括既往一线治疗、ECOG体能状态≤1和充分的器官功能。排除标准包括既往接受过PD-(L)1抑制剂治疗、副肿瘤血清学阳性或需要积极系统治疗的自身免疫性疾病。 Ivonescimab于21天周期的第1天静脉给药，直至疾病进展、不可耐受的毒性、退出或失访。主要终点为研究者确认的经RECIST 1.1的ORR以及ivonescimab的安全性/耐受性。次要终点包括无进展生存期、缓解持续时间、至缓解时间和总生存期。探索性分析将评估抗肿瘤活性与组织及血液来源生物标志物（如PD-L1表达和循环肿瘤DNA[ctDNA]）的相关性。研究采用Simon两阶段设计：在第1阶段，将入组15名患者。若发生≥5起治疗相关严重不良事件，或在治疗最初三个月内≤1名患者达到客观缓解，则研究将停止。否则，将在第2阶段额外入组10名患者。该设计在5%的I类错误下具有80%的把握度，以检测30%的ORR相对于10%的无效假设。该研究目前正在入组患者。临床试验信息：NCT06980077

查看英文原文 English abstract

Background: Thymic carcinoma (TC) is a rare and aggressive thymic epithelial tumor (TET), accounting for approximately 20% of thymic neoplasms. TC is often more invasive and less responsive to standard therapy than other TETs, with a 5-year survival rate of 30-50% in the advanced/metastatic setting. Effective treatment remains limited following progression with platinum-based chemotherapy. Programmed Death-(Ligand) 1 (PD-(L)1) inhibition demonstrates modest activity in recurrent TC, with an objective response rate (ORR) of 19.5-22.5% with manageable toxicities [Cho, Clin Oncol . 2019; Giaccone, J Thorac Oncol. 2021]. Moreover, vascular epithelial growth factor (VEGF) inhibition with sunitinib or lenvatinib achieved ORRs of 26-38% in second line therapy and beyond (Thomas, Lancet Oncol. 2015; Sato, Lancet Oncol. 2020). Combination of lenvatinib and pembrolizumab as second line therapy and beyond has shown an ORR of 22.5%, with a median duration of response of 8.2 months (Remon, Lancet Oncol. 2025 ). Ivonescimab is a humanized bispecific monoclonal antibody targeting both PD-1 and VEGF and shows favorable safety and efficacy in non-small cell lung cancer. In light of the known benefit of VEGF and PD-(L)1 blockade in TC, this study aims to evaluate the safety and efficacy of ivonescimab in patients with previously treated TC. Methods: This study is a multi-center, open-label, single-arm Phase II trial enrolling adults with histologically or cytologically confirmed unresectable/metastatic TC whose disease has progressed following systemic therapy. Key inclusion criteria include one-prior line of treatment, ECOG performance status ≤1, and adequate organ function. Exclusion criteria include prior treatment with PD-(L)1 inhibitors, positive paraneoplastic serologies, or autoimmune disease requiring active systemic therapy. Ivonescimab is administered intravenously on D1 of a 21-day cycle until disease progression, unacceptable toxicity, withdrawal, or loss of follow up. The primary endpoints are investigator confirmed ORR via RECIST 1.1 and safety/tolerability of ivonescimab. Secondary endpoints include progression-free survival, duration of response, time to response, and overall survival. Exploratory analyses will evaluate correlation of antitumor activity with tissue and blood-based biomarkers, such as PD-L1 expression and circulating tumor DNA (ctDNA). The study uses a Simon's two stage design: in stage 1, 15 patients will be enrolled. The study will be stopped if ≥ 5 treatment-related serious adverse events or if ≤1 patient achieves an objective response within the first three months of treatment. Otherwise, an additional 10 patients will be enrolled in stage 2. The design has 80% power with a 5% Type I error to detect an ORR of 30% over the null hypothesis of 10%. The study is currently enrolling patients. Clinical trial information: NCT06980077

利益披露 Disclosure

J. A. Boiarsky, Tectonic Therapeutics Stock. Immatics Stock. Compass Therapeutics Stock. C. Tseng, None. Z. Arter, Janssen Independent Contractor. AstraZeneca Independent Contractor. Rigel Pharmaceuticals Independent Contractor. Boehringer Ingelheim Independent Contractor. EMD Serono Independent Contractor. Catalyst Pharmaceuticals Independent Contractor. M. Gubens, AstraZeneca Independent Contractor. Bicycle Therapeutics Independent Contractor. BMS Independent Contractor. Cardinal Health Independent Contractor. Catalyst Independent Contractor. Foresight Independent Contractor. Genentech/Roche Independent Contractor. ohnson and Johnson Independent Contractor. Natera Independent Contractor. Nuvalent Independent Contractor. OncoHost Independent Contractor. Regeneron Independent Contractor. Samsung Bioepis Independent Contractor. Amgen ). Johnson and Johnson ). Merck ). Trizell ). C. Kim, AstraZeneca ). Novartis ). Regeneron ). Janssen ). Daiichi Sankyo ). Gilead ). Macrogenics ). Boehringer Ingelheim ). ORIC Pharmaceuticals ). BlossomHill Therapeutics ). AstraZeneca Independent Contractor. Daiichi Sankyo Independent Contractor. Eisai Independent Contractor. Regeneron Independent Contractor. Sanofi, Takeda Independent Contractor. Johnson and Johnson Independent Contractor. Pinetree Independent Contractor. Boehringer Ingelheim Independent Contractor. BMS Independent Contractor. Bicycle; Bayer; Onviv; Bio-Thera; Molecular Partners; Partner Therapeutic;, Natera; Guardant; EMD Serono; Mariana Oncology; Nuvation Bio; Delfi Diagnostics; Caris Life Sciences; Rayzebio; Henlius; P Independent Contractor. J. A. Marks, Merus Other, Advisory Board. Partners Advisory Board. Johnson & Johnson Advisory Board. AstraZeneca Advisory Board. Gilead Advisory Board. Regeneron Advisory Board. EMD Serono Advisory Board. Daiichi Sankyo Independent Contractor. Open Medicine Corp Stock. S. Singhal, BMS Advisory Board. Caris Life Sciences Other, Advisory Board. Foundation Medicine Other, Advisory Board. Janssen Pharmaceuticals Other, Advisory Board. Nuvalent Other, Advisory Board. C. Kivork, None.. L. Ikenouye, None. J. W. Goldman, AbbVie Independent Contractor, ). Agenus ). Amgen Independent Contractor, ). Astellas ). AstraZeneca Independent Contractor, ). BMS Independent Contractor, ). Eli Lilly Independent Contractor, ). Genentech Independent Contractor, ). GSK ). Janssen Independent Contractor, ). Merck ). Pfizer Independent Contractor, ). Puma ). RayzeBio ). Summit Independent Contractor, ). Tango ).

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