PO.CTP01.03 · 进行中的临床试验

一项1b/2a期研究，评估BXQ-350联合mFOLFOX7和贝伐珠单抗在新诊断转移性结直肠癌（mCRC）患者中的疗效和安全性：中期疗效亚组分析

A Phase 1b/2a study to evaluate the efficacy and safety of BXQ-350 in combination with mFOLFOX7 and bevacizumab in newly diagnosed metastatic colorectal carcinoma patients (mCRC): Interim efficacy subset analyses

编号 CT220 展板 15 时间 4/21 09:00–12:00 区域 Section 51 主讲 Daniel Flora

分会场 Phase II and Phase III Clinical Trials in Progress

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作者与单位 Authors & Affiliations

Daniel Flora¹, Ari Baron², Reema Patel³, Davendra Sohal⁴, Saima Sharif⁵, Fa Chyi Lee⁶, Julie Anne Gemmill⁷, Gilles H. Tapolsky⁸, James Beach⁸, Michael Gazda⁸, Tariq Arshad⁸

¹St Elizabeth Healthcare, Edgewood, KY,²Pacific Hematology, San Francisco, CA,³University of Kentucky, Lexington, KY,⁴University of Cincinnati, Cincinnati, OH,⁵University of Iowa, Iowa City, IA,⁶University of California Irvine, Orange, CA,⁷Stony Brook University, New York, NY,⁸Bexion Pharmaceuticals, Covington, KY

摘要 Abstract

中文摘要

背景：鞘脂代谢失调是包括mCRC在内的多种癌症类型的共同特征，可导致神经节苷脂（GM3）、乳糖神经酰胺（LacCer）、葡萄糖神经酰胺（GluCer）和1-磷酸鞘氨醇（S1P）浓度升高，以及神经酰胺（Cer）浓度降低。多项研究表明，在mCRC患者中，这些鞘脂浓度升高与更差的预后和不良生存相关。因此，靶向失调的鞘脂代谢并使鞘脂代谢恢复稳态可能是一种有前景的治疗方法。BXQ-350是Saposin C的纳米囊泡，Saposin C是鞘脂代谢的变构激活剂，可影响失调的鞘脂代谢。BXQ-350降低GM3、GluCer和S1P水平，同时也提高神经酰胺水平，促进恢复稳态。此外，有充分文献记载，在mCRC患者中，肿瘤部位（左右侧）、致癌突变和性别对预后有显著影响。多项报告提示，右侧患者的预后比左侧患者更差，绝经后女性总体上比同龄男性患者的预后更差。方法：BXQ-350正在一项1b/2a期研究中接受评估，联合mFOLFOX7和贝伐珠单抗（标准治疗，SoC）用于新诊断的mCRC患者（NCT05322590），以评估BXQ-350的疗效和安全性。1b/2a期是安全性剂量递增部分，旨在确立RP2D，探索1.8和2.4 mg/kg的BXQ-350联合SoC。主要目的是评估BXQ-350在该联合方案中的安全性和初步疗效。次要目的包括对多项生物标志物的纵向分析，包括鞘脂谱分析。结果：共入组32例可评估患者，全部32例患者已完成SoC治疗方案加BXQ-350。在这32例患者中，21例（66%）存活并处于积极随访中。32例患者中，19例为女性（59%），其中15例年龄在55岁或以上（79%）；15例为右侧结肠癌（47%），17例为左侧结肠癌和直肠癌患者。疾病控制率为91%（30例患者达到SD、PR或CR）。截至2025年9月，总体ORR和mPFS分别为61%和10.6个月；男性和女性患者的ORR分别为64.3%和52.6%，mPFS分别为9.1和10.6个月。右侧和左侧患者的ORR分别为60%和52.9%，mPFS分别为10.6和10.8个月。这些结果提示女性和右侧亚群的临床结局优于预期。结论：BXQ-350在该联合方案中安全且耐受性良好。中期分析和对患者的持续监测提示，BXQ-350可能带来额外的临床获益，尤其是在右侧或女性患者中，这体现于这些患者群体相比左侧或男性患者出现了出乎意料地优于预期的ORR或mPFS。

查看英文原文 English abstract

Background: Dysregulated sphingolipid metabolism is common to many cancer types, including mCRC, and leads to elevated concentrations of gangliosides (GM3), lactosylceramides (LacCer), glucosylceramides (GluCer) and sphingosine-1-phosphate (S1P) and lower concentration of ceramides (Cer). In mCRC patients, several studies have shown elevated concentrations of these sphingolipids are associated with worse prognosis and poor survival. Therefore, targeting dysregulated sphingolipid metabolism and returning sphingolipid metabolism to homeostasis could be a promising therapeutic approach. BXQ-350 is a nanovesicle of Saposin C, an allosteric activator of sphingolipid metabolism, that affects dysregulated sphingolipid metabolism. BXQ-350 lowers GM3, GluCer and S1P levels while it also increases ceramide levels promoting a return to homeostasis. Also, it is well documented that, in mCRC patients, sidedness, oncogenic mutations and sex have a significant impact on prognosis. Multiple reports suggest that right-sided patients have a worse prognosis than left-sided patients and post-menopausal females have, overall, a worse prognosis than male patients of a similar age. Method: BXQ-350 is being investigated in a Phase 1b/2a study in combination with mFOLFOX7 and Bevacizumab (SoC) in newly diagnosed mCRC patients (NCT05322590) to assess the efficacy and safety of BXQ-350. The Phase 1b/2a is a safety dose escalation part to establish the RP2D exploring 1.8 and 2.4 mg/kg BXQ-350 in combination with SoC. Primary objectives are to assess safety and preliminary efficacy of BXQ-350 in this combination. Secondary objectives include longitudinal analysis of several biomarkers, including sphingolipid profiling. Results: A total of 32 evaluable patients were enrolled, and all 32 patients have completed SoC treatment schedule plus BXQ-350. Amongst these 32 patients, 21(66%) are alive and in active follow-up. Of the 32 patients, 19 are female (59%) of which 15 are 55 years or older (79%); 15 are right-sided colon cancer (47%) and 17 are left-sided and rectal cancer patients. The disease control rate was 91% (30 pts had SD, PR or CR). As of September 2025, overall ORR and mPFS are 61% and 10.6 months; ORR for male and female patients are respectively 64.3% and 52.6% while mPFS 9.1 and 10.6 months respectively. ORR and mPFS for right-sided and left-sided patients are 60% and 52.9% respectively and mPFS 10.6 and 10.8 months. These results suggest a better than expected clinical outcome in female and right-sided subpopulations. Conclusions: BXQ-350 was safe and well tolerated in the combination. Interim analyses and ongoing monitoring of patients suggests that BXQ-350 may provide additional clinical benefits, especially in right-sided or female patients as illustrated by surprisingly better than expected ORR or mPFS in these patient populations compared to left-sided or male patients

利益披露 Disclosure

D. Flora, None.. A. Baron, None.. R. Patel, None.. D. Sohal, None.. S. Sharif, None.. F. Lee, None.. J. Gemmill, None. G. H. Tapolsky, Bexion Pharmaceuticals Employment, Stock, Stock Option, Patent. J. Beach, Bexion Pharmaceuticals Employment, Stock, Stock Option. M. Gazda, Bexion Pharmaceuticals Employment, Stock, Stock Option. T. Arshad, Bexion Pharmaceuticals Employment, Stock, Stock Option.

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