PO.CTP01.01 · 进行中的临床试验
CAN2109（一种新型、长效、肿瘤滞留型免疫原性细胞死亡诱导剂）的1期研究
A phase 1 study of CAN2109, a novel,long-acting, tumor-retained, immunogenic cell death inducer
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
这项正在进行的3+3剂量爬坡1期研究（NCT06332430/CTR20241484）纳入了年龄≥18岁、至少有一处可测量且可进行病灶内注射的实体瘤患者（pts）。主要终点为每3周（Q3W）给药的CAN2109的安全性，以MTD和RP2D来定义。次要终点为药代动力学、药效动力学和初步疗效。方法与结果 截至2025年12月16日，19例患者（既往接受1-7线治疗，中位3线治疗），年龄28-66岁（中位48岁），涵盖晚期/转移性乳腺癌（MBC）（7例HER2+、6例HER2-）、黑色素瘤（1例）、肉瘤（2例）、甲状腺癌（1例）、腺样囊性癌（1例）和皮脂腺癌（1例），被分为4个队列之一进行治疗：0.5 mg（3例）、1.0 mg（3例）、2.0 mg（10例）和4.0 mg（3例）。最常见的不良事件为注射部位局部肿胀、疼痛和炎症，多为1级或2级（Gr.），通过局部短暂使用地塞米松即可控制。在2.0 mg剂量的MBC患者中，于引入地塞米松之前曾报告2例3级事件（其中1例为伴局部感染的溃疡）。全身方面，仅观察到1级或2级全身不良事件，其中3例发热、2例ALT升高、2例厌食、1例呕吐、1例乏力。CAN2109给药后大部分滞留于肿瘤内，血浆暴露量极低。IP10在2.0 mg剂量以内随剂量成比例升高。基线时肿瘤内更高的CD3、CD8和FOXP3细胞浸润似乎与更高的缓解率相关。MTD被确定为4.0 mg Q3W，RP2D被确定为2.0 mg Q3W。RP2D队列已进行扩展。总体而言，4例患者出现部分缓解（PR），7例患者疾病稳定（SD），总缓解率（ORR）为22%，疾病控制率（DCR）为61%。所有缓解者均在2 mg剂量队列接受治疗，在共7例HER2+ MBC中，报告了4例PR和2例SD（ORR = 57%；DCR = 86%）。值得注意的是，在5例既往ADC治疗失败的MBC患者中，出现3例PR和1例SD。在5例接受过重度预处理的患者中观察到远隔效应，包括骨、肺和淋巴结转移灶的缩小或消失。结论 CAN2109是一种肿瘤锚定型免疫原性细胞死亡（ICD）诱导剂，可用于实体瘤患者且毒性可控。初步疗效数据表明其在晚期HER2+ MBC中具有活性，其中部分患者既往ADC治疗已失败。RP2D队列扩展正在进行中。
查看英文原文 English abstract
The ongoing 3+3 Phase 1 study (NCT06332430/CTR20241484) enrolled solid tumours patients (pts) aged ≥18 years with at least one measurable lesion accessible for intra-lesional injection. The primary endpoint was the safety of CAN2109 administered Q3W defined as MTD and RP2D. Secondary endpoints were pharmacokinetics, pharmacodynamics and preliminary efficacy. Methods and Results As of December 16 2025, 19 pts (1-7 previous therapies, median 3 therapies) aged 28-66 years (median 48 years) with advanced/metastatic breast cancer (MBC) (7 HER2+, 6 HER2-), melanoma (1), sarcoma (2), thyroid (1), adenoid cystic (1) and sebaceous gland cancer (1) had been treated as 1 of 4 cohorts, 0.5mg (3 pts), 1.0 mg (3 pts), 2.0 mg (10 pts) and 4.0 mg (3 pts). The most common adverse events reported were local swelling, pain and inflammation at the injection site, mostly grade (Gr.) 1 or 2, controlled by transient dexamethasone employment locally. Two Gr. 3 event (ulceration with local infection in one pt) had been reported before dexamethasone introduction in MBC pts at 2.0 mg. Systemically, only Gr. 1 or 2 systemic adverse events have been observed, with 3 pts experiencing fever, 2 pts ALT increase, 2 pts anorexia, 1 pt vomiting and 1 pt fatigue. CAN2109 was mostly retained in the tumor after administered, with very low exposure in plasma. IP10 increased proportionally up to the dose of 2.0 mg. Higher CD3, CD8 and FOXP3 cells infiltration in tumour at baseline seemed to correlate with higher response rate. The MTD has been defined as 4.0 mg Q3W, and the RP2D as 2.0 mg Q3W. The RP2D cohort was expanded. Overall, 4 pts experienced a partial tumour response (PR) and 7 pts a disease stabilisation (SD), representing for a 22% overall response rate (ORR) and a 61% disease control rate (DCR). All the responders were treated in the 2mg dose cohort, and out of the total of 7 HER2+ MBC, 4 PR and 2 SD (ORR = 57%; DCR = 86%) were reported. Importantly, out of 5 MBC who had failed previous ADC treatments, 3 PR and 1 SD were shown. Abscopal effects were observed in 5 pts who received heavy pre-treatments, including the shrinkage or disappearance of metastases in bones, lungs and lymph nodes. Conclusion CAN2109 is a tumor-anchoring immunogenic cell death (ICD) inducer that can be administered to solid tumor pts with manageable toxicity. Preliminary efficacy data indicate activity in late stage HER2+ MBC, with some pts who failed previous ADC treatment. The RP2D cohort expansion is ongoing.
利益披露 Disclosure
H. Yao, None..
N. Li, None..
H. N. Yu, None..
G. Massimini, None..
J. Zhao, None..
S. Wang, None..
Y. Zhao, None..
Y. Yu, None..
X. Lai, None..
X. Lv, None..
S. Wang, None..
X. Guo, None..
J. Huang, None..
F. Tan, None..
E. Song, None.