PO.CT01.05 · 临床试验

surufatinib联合信迪利单抗和卡培他滨治疗既往经治的转移性小肠腺癌和阑尾癌的更新多中心Ib/II期分析

Updated multicenter phase Ib/II analysis of surufatinib plus sintilimab and capecitabine in previously treated metastatic small bowel adenocarcinoma and appendiceal carcinoma

编号 CT160 展板 24 时间 4/20 02:00–05:00 区域 Section 52 主讲 Xiaoyu Xie, MD

分会场 Phase II and Phase III Clinical Trials

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作者与单位 Authors & Affiliations

Xiaoyu Xie¹, Jianwei Zhang¹, Yue Cai¹, Xiaohui Lin², Huabin Hu¹, Jiayu Lin¹, Yan Zhang¹, Shanshan Li¹, Bohan Han¹, Yanhong Deng¹

¹The Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China,²People’s Hospital of Shenzhen Baoan District, The Second Affiliated Hospital of Shenzhen University, Shenzhen, China

摘要 Abstract

中文摘要

背景：小肠腺癌（SBA）和阑尾癌是罕见的胃肠道恶性肿瘤，无既定的二线标准治疗。大多数患者（pts）在FOLFOX为基础的化疗后迅速进展，pMMR/MSS肿瘤从单纯PD-1阻断中获益极小。surufatinib（Suru）是一种靶向VEGFR1-3、FGFR1和CSF-1R的多靶点酪氨酸激酶抑制剂，可能主要通过血管正常化和免疫微环境重编程增强抗肿瘤免疫。我们此前报告了剂量限制性毒性、Ib期确定的推荐II期剂量（RP2D），以及在AACR 2025上呈现的9例患者的初步疗效和安全性数据。在此我们呈现迄今入组的15例患者的疗效和安全性更新分析。方法：这项正在进行的多中心、单臂、Ib/II期试验入组≥1线既往全身治疗后进展的不可切除SBA或阑尾癌患者。Ib期采用3+3设计，测试Suru 200 mg口服每日一次（剂量水平1；DL1）和250 mg口服每日一次（DL2）于第1-21天，联合信迪利单抗（Sin）200 mg静脉给药于第1天和卡培他滨（Cap）1000 mg/m²口服每日两次于第1-14天，每3周（q3w）。在II期，患者接受RP2D剂量的Suru（250 mg口服每日一次，如Ib期确定）加Sin和Cap。整体研究的主要终点为无进展生存（PFS）；次要终点包括总生存（OS）、客观缓解率（ORR）、疾病控制率（DCR）和安全性。结果：15例患者在两个中心入组。中位年龄为57.8岁，73.3%为女性。7例（46.7%）为SBA，8例（53.3%）为阑尾癌。腹膜转移几乎普遍存在（93.3%），46.7%曾接受≥2线既往治疗。最佳总体应答为1例PR（6.7%）、8例SD（53.3%）和6例PD（40.0%），ORR为6.7%，DCR为60.0%。在数据截止时（2026年1月1日），发生了10起PFS事件和6例死亡；中位PFS为3.3个月（95% CI，2.0-4.5），中位OS为19.5个月（95% CI，8.1-31.0）。2例患者PFS>6个月，4例存活>12个月。安全性与既往中期数据一致。2例患者发生3级治疗相关不良事件（TRAE）：一例达PR者出现甲状腺功能减退和肾上腺功能不全；另一例出现腹泻、手足综合征和黏膜炎。所有其他TRAE均为1-2级。未发生4-5级TRAE或治疗相关死亡。结论：Suru联合Sin和Cap在既往经治的SBA和阑尾癌中显示出可接受的耐受性和初步的抗肿瘤活性。持续入组和分子相关性分析可能有助于阐明持久性并识别最可能获益的亚组。ClinicalTrials.gov编号：NCT05472948

查看英文原文 English abstract

Background: Small bowel adenocarcinoma (SBA) and appendiceal carcinoma are rare gastrointestinal malignancies with no established second-line standard. Most patients (pts) progress rapidly following FOLFOX-based chemotherapy, and pMMR/MSS tumors derive minimal benefit from PD-1 blockade alone. Surufatinib (Suru), a multi-target tyrosine kinase inhibitor of VEGFR1-3, FGFR1, and CSF-1R, may enhance antitumor immunity primarily through vascular normalization and reprogramming of the immune microenvironment. We previously reported the dose-limiting toxicities, the recommended phase II dose (RP2D) determined in phase Ib, and preliminary efficacy and safety data from 9 pts presented at AACR 2025. Here we present an updated analysis of efficacy and safety in the 15 pts enrolled to date. Methods: This ongoing multicenter, single-arm, phase Ib/II trial enrolls pts with unresectable SBA or appendiceal carcinoma who have progressed after ≥1 prior systemic therapy. Phase Ib used a 3+3 design testing Suru 200 mg p.o. once daily (dose level 1; DL1) and 250 mg p.o. once daily (DL2) on days 1-21, combined with sintilimab (Sin) 200 mg i.v. on day 1 and capecitabine (Cap) 1000 mg/m² p.o. twice daily on days 1-14, every 3 weeks (q3w). In phase II, pts receive Suru at the RP2D (250 mg p.o. once daily, as established in phase Ib) plus Sin and Cap. The primary endpoint for the overall study is progression-free survival (PFS); secondary endpoints include overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Results: 15 pts were enrolled across two centers. Median age was 57.8 years, and 73.3% were female. 7 pts (46.7%) had SBA and 8 (53.3%) had appendiceal carcinoma. Peritoneal metastasis was nearly universal (93.3%), and 46.7% had received ≥2 prior lines of therapy. Best overall response was PR in 1 patient (6.7%), SD in 8 pts (53.3%), and PD in 6 pts (40.0%), yielding an ORR of 6.7% and a DCR of 60.0%. At the data cutoff (January 1, 2026), 10 PFS events and 6 deaths had occurred; median PFS was 3.3 months (95% CI, 2.0-4.5) and median OS was 19.5 months (95% CI, 8.1-31.0). 2 pts had PFS >6 months, and 4 remained alive >12 months. Safety was consistent with prior interim data. 2 pts experienced grade 3 treatment-related adverse events (TRAEs): one with PR developed hypothyroidism and adrenal insufficiency; the other had diarrhea, hand-foot syndrome, and mucositis. All other TRAEs were grade 1-2. No grade 4-5 TRAEs or treatment-related deaths occurred. Conclusions: Suru plus Sin and Cap demonstrated acceptable tolerability and preliminary antitumor activity in pretreated SBA and appendiceal carcinoma. Ongoing enrollment and molecular correlative analyses may clarify durability and identify subgroups most likely to benefit. ClinicalTrials.gov No.: NCT05472948

利益披露 Disclosure

X. Xie, None.. J. Zhang, None.. Y. Cai, None.. X. Lin, None.. H. Hu, None.. J. Lin, None.. Y. Zhang, None.. S. Li, None.. B. Han, None.. Y. Deng, None.

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