PO.CL05.06 · 临床研究

leronlimab联合TAS-102和贝伐珠单抗治疗既往接受过治疗的转移性结直肠癌的一项2期研究的初步结果

Preliminary results of a phase 2 study of leronlimab in combination with TAS-102 and bevacizumab in previously treated metastatic colorectal cancer

编号 6466 展板 14 时间 4/21 02:00–05:00 区域 Section 41 主讲 Pashtoon Kasi, MD;MS

分会场 Clinical Correlates of Immunotherapy

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作者与单位 Authors & Affiliations

Pashtoon M. Kasi¹, Ari Baron², Arvind Chaudhry³, Laura Tenner⁴, Daniel L. Adams⁵, Alexis B. Duffy⁶, Hallgeir Rui⁷, Patrick Vittner⁸, Joseph Meidling⁸, Jacob P. Lalezari⁸

¹City of Hope Comprehensive Cancer Ctr., Duarte, CA,²Division of Hematology Oncology, Sutter/California Pacific Medical Center, San Francisco, CA,³Summit Cancer Centers, Spokane, WA,⁴University of Nebraska Medical Center, Fred and Pamela Buffett Cancer Center, Omaha, NE,⁵Creatv MicroTech, Monmouth Junction, NJ,⁶Creatv MicroTech, Inc., Rockville, MD,⁷Thomas Jefferson University, Philadelphia, PA,⁸CytoDyn Inc., Vancouver, WA

摘要 Abstract

中文摘要

背景：CCR5促进免疫抑制性髓系细胞群的募集，并在转移性结直肠癌（mCRC）中参与免疫逃逸。Leronlimab是一种靶向CCR5的人源化单克隆抗体，具有免疫激活作用。TAS-102联合贝伐珠单抗是难治性mCRC的标准方案。本研究评估leronlimab联合TAS-102/贝伐珠单抗的安全性，以及该联合方案是否通过免疫激活提高客观缓解率。方法：这项正在进行的多中心2期试验将入组最多60例既往接受过治疗的mCRC患者。Leronlimab起始剂量为350 mg皮下注射每周一次，与标准剂量的TAS-102/贝伐珠单抗联用。在基线时通过免疫组织化学对肿瘤样本评估CCR5表达和PD-L1 CPS。在血样中的循环肿瘤细胞（CTCs）和癌症相关巨噬细胞样细胞（CAMLs）中评估PD-L1和CCR5。结果：在所有具有可评估存档样本的预筛查患者中，33/33（100%）显示出CCR5表达。截至2025年11月17日，已在6个中心入组10例患者，初步基线和生物标志物数据见表1。在希望之城（City of Hope）中心，4/4例患者（有数据者）出现临床和/或生物标志物应答，即CEA、CA19-9和/或ctDNA下降，尽管存在难治性肝转移疾病。连续动力学显示，治疗1周后CTCs和CAMLs上的PD-L1增加，而应答者中CAMLs和CTCs的数量降低。Leronlimab耐受性良好，无意外的安全性信号。这份初步试验报告的入组进度超前，反映了mCRC疾病中巨大的未满足需求。结论：leronlimab联合TAS-102和贝伐珠单抗是可行的，在既往接受大量治疗的mCRC中显示出有前景的早期生物标志物和临床活性。普遍的CCR5阳性支持将CCR5作为潜在的治疗靶点。将展示更新的结局和相关数据。表参数结果种族（N=10）西班牙裔 n=1；非西班牙裔 n=9 性别（N=10）男性 n=6；女性 n=4 平均年龄（N=10）54.3岁平均体重（N=10）100.2 kg 基线CTCs：中位数（范围）* 0（0-2）基线CAMLs：中位数（范围）* 47（1-67）随访CTCs：中位数（范围）* 0（0-4）随访CAMLs：中位数（范围）* 31（1-87）CAMLs或CTCs中PD-L1增加* 60%（n=3/5）* 5例同时具有基线和第1周数据的患者

查看英文原文 English abstract

Background: CCR5 promotes recruitment of immunosuppressive myeloid populations and contributes to immune evasion in metastatic colorectal cancer (mCRC). Leronlimab is a humanized monoclonal antibody targeting CCR5 with immune-activating effects. TAS-102 plus bevacizumab is a standard regimen in refractory mCRC. This study evaluates the safety of leronlimab in combination with TAS-102/bevacizumab and if this combination enhances objective response rates via immune activation. Methods: This ongoing multicenter Phase 2 trial will enroll up to 60 previously treated mCRC patients. Leronlimab will be initially dosed 350 mg SC QW with TAS-102/bevacizumab at standard doses. CCR5 expression and PD-L1 CPS is assessed by immunohistochemistry on tumor samples at baseline. PD-L1 and CCR5 is assessed in circulating tumor cells (CTCs) and cancer associated macrophage-like cells (CAMLs) from blood samples. Results: Among all pre-screened patients with evaluable archival samples, 33/33 (100%) demonstrated CCR5 expression. As of 11/17/ 2025, 10 patients have been enrolled across 6 sites, with preliminary baseline and biomarker data in Table 1. At the City of Hope site, 4/4 patients (with data) had clinical and/or biomarker responses, i.e. declines in CEA, CA19-9, and/or ctDNA, despite refractory liver-metastatic disease. Serial kinetics showed an increase in PD-L1 on CTCs and CAMLs after 1 week on treatment, while the number of CAMLs and CTCs lowered in responders. Leronlimab has been well tolerated, with no unexpected safety signals. This preliminary trial report, which is enrolling ahead of pace, reflects a high unmet need in mCRC disease. Conclusions: Leronlimab combined with TAS-102 and bevacizumab is feasible, showing promising early biomarker and clinical activity in heavily pretreated mCRC. Universal CCR5 positivity supports CCR5 as a potential therapeutic target. Updated outcomes and correlative data will be presented. Table Parameter Result Ethnicity (N=10) Hispanic n=1; Non-Hispanic n=9 Sex (N=10) Male n=6; Female n=4 Mean age (N=10) 54.3 years Mean weight (N=10) 100.2 kg CTCs at baseline: median (range)* 0 (0-2) CAMLs at baseline: median (range)* 47 (1-67) CTCs at follow-up: median (range)* 0 (0-4) CAMLs at follow-up: median (range)* 31 (1-87) PD-L1 increase in CAMLs or CTCs* 60% (n=3/5) * 5 patients with both baseline and Week 1 data

利益披露 Disclosure

P. M. Kasi, Eilcio Other, Scientific/Advisory Board. Agenus Other, Advisory Board. Astellas Pharma Other, Consultancy/Advisory Board. Astra Zeneca Other, Consultancy/Advisory Board. Bayer Other, Consultancy/Advisory Board. Beixon Pharma Other, Consultancy/Advisory Board. BostonGene Other, Consultancy/Advisory Board. Daiichi Sankyo Other, Consultancy/Advisory Board. Delcath Systems Other, Consultancy/Advisory Board. Eli Lilly Other, Consultancy/Advisory Board. Eisai Other, Consultancy/Advisory Board. Elico Therapeutics Other, Consultancy/Advisory Board. Exact Sciences Other, Consultancy/Advisory Board. Foundation Medicine Other, Consultancy/Advisory Board. Guardant Other, Consultancy/Advisory Board. Illumina Other, Consultancy/Advisory Board. Ipsen Other, Consultancy/Advisory Board. Merck/MSD Other, Consultancy/Advisory Board. Natera, Neogenomics, QED, Regeneron, SAGA Diagnostics, Seagen, Servier, Taiho Oncology, Tempus, Xilio Therapeutics Other, Consultancy/Advisory Board. Agenus, Merck, Novartis ). A. Baron, BMS Other, Speaker Bureau. Bayer Other, Speaker Bureau. AbbVie Other, Speaker Bureau. A. Chaudhry, novartis Stock, Other, speaker bureau. L. Tenner, None. D. L. Adams, Creatv MicroTech Employment, Stock. A. B. Duffy, Creatv MicroTech Employment, Stock. H. Rui, IHG Biosciences Independent Contractor, Stock. mIRoncol Independent Contractor, Stock. Advantex Bioreagents Independent Contractor, Stock. CytoDyn Independent Contractor, Other, Consultant. P. Vittner, CytoDyn Inc. Employment. J. Meidling, CytoDyn Inc. Employment, Stock. J. P. Lalezari, CytoDyn Inc. Employment, Stock.

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