A Phase 1a/1b, Open-label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Anti-neoplastic Activity of S095029 (Anti-NKG2A) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies Followed by an Expansion Part With Triplet Combinations of S095029 and Sym021 and an Anti-HER2 mAb or Anti-EGFR mAbs (Futuximab/Modotuximab) in Patients With Metastatic Gastric or Colorectal Cancers

The purpose of the study is to investigate the safety, tolerability, and preliminary anti-neoplastic activity of S095029 alone and in combination with Sym021 in patients with advanced solid tumor malignancies followed by an expansion phase of triple combinations.
*The study sponsor has made the decision not to move forward to the expansion part of the study due to strategic considerations, unrelated to any safety issues or concerns. The study will be stopped after completion of dose escalation parts 1a and 1b of the study.

开始日期2021-10-15

申办/合作机构

Institut de Recherches Intern Servier

[+1]

NCT04195373

/ Withdrawn临床1期

A Phase I Open-label, Safety Study of Intra-tumoral Application of TMV-018 in Combination With 5-FC or Anti-PD-1 Therapy in Patients With Tumors of the Gastrointestinal Tract

This study aims to determine the safety and tolerability of TMV-018 when given alone or in combination with the prodrug 5-Fluorocytosine (5-FC) or an anti-PD-1 checkpoint inhibitor in patients with gastrointestinal tumors. Furthermore, the maximum tolerated dose (MTD) and recommended Phase II dose of TMV-018 shall be determined.

开始日期2020-11-23

申办/合作机构

Themis Bioscience GmbH

[+2]

NCT04672434

/ Completed临床1期

A Phase 1, Open-Label, Multicenter Trial Investigating the Safety, Tolerability, and Preliminary Antineoplastic Activity of Sym024 (Anti-CD73) as Monotherapy and in Combination With Sym021 (Anti-PD-1) in Patients With Advanced Solid Tumor Malignancies

The primary purpose of this study is to see if Sym024 is safe and tolerable as monotherapy and in combination with Sym021 in patients with solid tumor malignancies.

开始日期2020-11-19

申办/合作机构

Servier Symphogen A/S

100 项与 Sym-021 相关的临床结果

登录后查看更多信息

100 项与 Sym-021 相关的转化医学

登录后查看更多信息

100 项与 Sym-021 相关的专利（医药）

登录后查看更多信息

项与 Sym-021 相关的文献（医药）

2026-03-01·Journal for ImmunoTherapy of Cancer

Phase Ib multicenter study of anti-TIM-3 (S095018/Sym023) in combination with anti-PD-1 (Sym021) in patients with advanced/metastatic recurrent biliary tract cancer

Article

作者: Skartved, Niels ; Lakhani, Nehal ; Geronimi, Julia ; Darcel, Pauline ; Rodrigues, Christelle ; Rodon Ahnert, Jordi ; Harouki, Najah ; Kim, Richard ; Askoxylakis, Vasileios ; Raimbourg, Judith ; Hald, Rikke ; Ianopoulos, Xenophon ; Kaplon, Hélène ; Marron, Thomas ; Moreno, Irene ; Liao, Chih-Yi ; Macarulla, Teresa ; He, Peng ; Davis, Sarah Lindsey ; Jakobsen, Janus Schou ; Ghiringhelli, Francois ; Abdul Razak, Albiruni ; Mahipal, Amit ; Lopez-Ravnborg, Daleen

Background:

T-cell immunoglobulin and mucin-domain containing 3 (TIM-3) is an inhibitory receptor linked to decreased antitumor activity of immune cells. S095018 is a human anti-TIM-3 IgG2 antibody that blocks the binding of phosphatidyl serine to TIM-3. Sym021 is a humanized IgG1 antibody that inhibits the binding of programmed cell death protein-1 (PD-1) to its ligands programmed death-ligand 1 (PD-L1) and PD-L2.

Methods:

S095018 in combination with Sym021 was tested in patients with advanced/metastatic biliary tract cancers (BTC) whose disease progressed under treatment with at least 1 line of systemic therapy and who had not received prior treatment with PD-(L)1 inhibitors ( NCT04641871 ). Patients received 3 mg/kg of Sym021 and 10 mg/kg of S095018 once every 2 weeks. Primary endpoints included overall response rate and incidence/severity of adverse events. Key secondary endpoints included pharmacokinetics, immunogenicity assessment, progression-free survival (PFS) and overall survival (OS).

Results:

35 patients with stage IV BTC received S095018 in combination with Sym021. A partial response was achieved in 2 patients (5.7%) and stable disease in 11 patients (31.4%) for a disease control rate of 37%; 4 patients were not evaluable for response. Median PFS and OS were 1.9 months (90% CI 1.8 to 3.7) and 13.4 months (90% CI 8.2 to 27.1), respectively. The most common treatment-emergent adverse events of any grade included fatigue, pruritus, infusion-related reaction, and increases in amylase (8.6% each). Exploratory biomarker analyses in paired tumor biopsies showed an increase in intratumoral CD8 T-cell density and an upregulation of gene signatures related to interferon-γ signaling, antigen presentation, and T-cell activation with treatment without, however, clear association with efficacy endpoints.

Conclusions:

Dual PD-1/TIM-3 inhibition was tolerable but exhibited modest antitumor activity in patients with advanced/metastatic recurrent BTC who had not received prior anti-PD-(L)1 treatment.

2024-09-20·Nan fang yi ke da xue xue bao = Journal of Southern Medical University

[High RNF7 expression enhances PD-1 resistance of non-small cell lung cancer cells by promoting CXCL1 expression and myeloid-derived suppressor cell recruitment via activating NF-κB signaling].

Article

作者: Zhong, N ; Geng, B ; Sun, Z ; Zhao, W ; Wang, H

OBJECTIVE:

To investigate the mechanism of RNF7 for regulating myeloid-derived suppressor cells (MDSCs) in nonsmall cell lung cancer (NSCLC).

METHODS:

TIMER2.0 database and immunohistochemistry were used to analyze RNF7 expression level and its correlation with immune cell infiltration in non-small cell lung cancer. The impact of RNF7 expression levels on prognosis of lung cancer patients was analyzed using Kaplan-Meier survival analysis. CMT-167 cells with RNF7 overexpression or knockdown were inoculated subcutaneously in C57BL/6 mice, and the mice in RNF7 knockdown group were treated with anti-PD-1 or IgG isotype control 7 days after the inoculation. The tumor tissues were harvested after 30 days for tumor volume measurement, detection of S100A8+A9 and Gr-1 expressions with immunohistochemistry, and analysis of MDSC infiltration. Gene set enrichment analysis (GSEA) was performed to identify the potential pathways regulated by RNF7 in NSCLC. Western blotting and luciferase assays were used to assess the impact of RNF7 on the NF-κB signaling pathway. ELISA and RT-qPCR were used to measure chemokine (C-X-C motif) ligand 1 (CXCL1) expression.

RESULTS:

RNF7 expression was significantly upregulated in NSCLC, and high RNF7 expression levels were associated with poor prognosis of the patients (P < 0.001). TIMER2.0 analysis revealed a positive correlation between RNF7 expression and MDSC infiltration (P < 0.001). GSEA suggested that RNF7 was enriched in the NF-κB signaling pathway. In NSCLC cells, RNF7 knockdown significantly inhibited NF-κB activation and reduced CXCL1 expression. In the tumor-bearing mice, RNF7 overexpression significantly increased MDSC infiltration in the tumor tissue, and RNF7 knockdown obviously reduced MDSC infiltration and enhanced the efficacy of anti-PD-1 therapy.

CONCLUSION:

High expression of RNF7 in NSCLC cells promotes CXCL1 expression by activating the NF-κB signaling pathway, thus leading to the chemotactic recruitment of MDSCs, which contributes to tumor resistance to antiPD-1 therapy.

2020-12-01·Journal of hematology & oncology1区 · 医学

CDK7 inhibitor THZ1 enhances antiPD-1 therapy efficacy via the p38α/MYC/PD-L1 signaling in non-small cell lung cancer

1区 · 医学

ArticleOA

作者: Dong, Xiaorong ; Wu, Gang ; Chen, Yaobing ; Zhou, Xiaoshu ; Xu, Shuangbing ; Zhang, Tao ; Meng, Rui ; Liu, Li ; Hong, Jiaxin ; Zhang, Sheng ; Wang, Jian ; Zhang, Ruiguang ; Tang, Jing ; Lin, Zhenyu ; Zong, Yan ; Yang, Kunyu ; Xu, Yingzhuo

Abstract:

Background:

The cyclin-dependent kinase 7 (CDK7) subunit of TFIIH regulates RNA polymerase-II-based transcription and promotes tumor progression. However, the mechanisms involved in CDK7-mediated immune evasion are unclear in non-small cell lung cancer (NSCLC).

Methods:

RNA silencing and pharmacologic inhibitors were used to evaluate the functions of CDK7/p38α/MYC/PD-L1 axis in cancer cell proliferation and antiPD-1 therapy resistance. Flow cytometry was performed to detect the status of the immune microenvironment after CDK7 inhibition and antiPD-1 therapy in vivo. CD8 depletion antibodies were used to assess the role of CD8+ T cells in combined CDK7 and PD-1 blockade. The associations among CDK7, p38α, MYC, PD-L1, infiltrating T cells, and survival outcomes were validated in two tissue microarrays and public transcriptomic data of NSCLC.

Results:

High CDK7 mRNA and protein levels were identified to be associated with poor prognosis in NSCLC. CDK7 silencing and CDK7 inhibitor THZ1 elicited apoptosis and suppressed tumor growth. Moreover, CDK7 ablation specifically suppressed p38α/MYC-associated genes, and THZ1 inhibited MYC transcriptional activity through downregulating p38α. CDK7 inhibition sensitized NSCLC to p38α inhibitor. Further, THZ1 suppressed PD-L1 expression by inhibiting MYC activity. THZ1 boosted antitumor immunity by recruiting infiltrating CD8+ T cells and synergized with antiPD-1 therapy. The CDK7/MYC/PD-L1 signature and infiltrating T cell status collectively stratified NSCLC patients into different risk groups.

Conclusion:

These data suggest that the combined CDK7 inhibitor THZ1 and antiPD-1 therapy can be an effective treatment in NSCLC.

107

项与 Sym-021 相关的新闻（医药）

2026-10-26

·VIP说

惊艳ESMO！芦康沙妥珠单抗+免疫的“替代化疗”策略再迎突破性进展：PFS达15个月，生存获益引关注-正面硬刚免疫+化疗，即将成为一线新标准

继OptiTROP-Lung05研究在ASCO中交出了一份足以震撼整个肺癌领域的成绩单后，芦康沙妥珠单抗带着OptiTROP-Lung06 研究又重磅登场 2026 ESMO LBA（想到数据好，但是没想到能这么好！）让我们也一起看看这份成绩单。划重点 1 最佳生存获益：中位随访时间9.7 个月，在sac-TMT + P 组中，BICR 评估的 PFS 显著超过 P 组（15.0个月vs. 5.7 个月；HR 0.49；95% CI, 0. 36~0.65 ; p<0.0001）[1]，是对照组的 3 倍，超越 PD-(L) 1联合化疗的 SOC 治疗方案。 2 更优缓解：中位DoR和12 个月 DoR 率均翻倍，中位DoR为13.6个月和6.8个月（HR 0.47；95% CI 0.29-0.77），12个月DoR 率为 61.7% vs 27.2%。 3 更优安全性：≥3级TEAEs 和停药率均更低，其中≥3级TEAEs 分别为47.6% vs 60.6%，停药率分别为5.7% vs 14.2%。 01 直击PD-L1阴性“硬骨头”！当疗效遭遇瓶颈，ADC+IO能否改写一线格局？驱动基因阴性PD-L1阴性晚期非鳞NSCLC是公认的难治人群，常表现出免疫细胞浸润不足、肿瘤免疫微环境相对“冷”等特征，往往面临“单药疗效有限、联合化疗毒性增加” 的两难困境。其中免疫联合化疗对比化疗的III期研究亚组分析中，PD-L1 阴性非鳞人群整体mPFS提升有限，仅6-8个月，联合方案3级以上不良事件率达70%甚至更高[2-6]。疗效突破有限，治疗负担却难以减轻。图1. 不同PD-1联合联合化疗一线治疗PD-L1阴性非鳞NSCLC亚组分析为了啃下这块难治的“硬骨头”，医学界从未停止探索。免疫治疗持续“加码”，却始终难破一年PFS瓶颈！从双免、双抗到免疫联合抗血管生成治疗，创新方案不断涌现，然而免疫治疗的“加法”越做越多，生存获益的突破却远没有想象中容易。PD-L1阴性人群的mPFS仍难突破一年[7-12]，部分方案仍然无法摆脱传统化疗，疗效提升与毒性负担之间的矛盾依然存在。免疫治疗不断升级，却依然难以跨越疗效天花板，一个更具颠覆性的问题摆在了临床面前：突破PD-L1阴性治疗困境，真的只能继续在免疫治疗上做“加法”吗？图2. 双免/双抗±化疗及免疫联合抗血管生成治疗±化疗在PD-L1阴性人群中的mPFS 02 跳出免疫“内卷”！与其不断叠加治疗，不如重新定义联合策略如果真正需要改变的，不是免疫治疗本身，而是与免疫治疗并肩作战的另一半呢？这一思路，正在推动晚期NSCLC一线治疗迎来新的变革。以ADC替代传统化疗，让精准靶向杀伤与免疫治疗协同发力，或许正是突破现有治疗困局的关键。从“免疫+化疗”到“ADC+免疫”，改变的不仅是联合方案中的一款药物，更可能是一线治疗的底层逻辑。而以芦康沙妥珠单抗（sac-TMT）为代表的创新TROP2 ADC开展的2项研究，成为全球首个应用于驱动基因阴性NSCLC人群显著获益的ADC+IO的III期研究，不断验证这一全新策略。从ASCO到ESMO，从PD-L1阳性到阴性：05、06研究接力，ADC+IO迎来关键突破！06研究头对头硬战免疫联合化疗！mPFS 达15个月， OS 积极信号初现。 2026年ASCO大会上，OptiTROP-Lung05研究率先交出亮眼答卷[13]。芦康沙妥珠单抗联合帕博利珠单抗在PD-L1阳性晚期NSCLC人群中展现出显著的PFS获益，疾病进展或死亡风险降低65%（HR=0.35；95% CI：0.26–0.47；P<0.0001）。尽管中期分析时mPFS尚未达到，但模型预测mPFS超过16个月，为ADC+IO替代传统化疗提供了重要的临床证据。 2026年ESMO大会，OptiTROP-Lung06研究以LBA重磅亮相，直接对标免疫联合化疗标准方案，向一线治疗格局发起正面挑战！结果令人振奋： mPFS达到15.0个月，对照组仅为5.7个月！疾病进展或死亡风险降低51%（HR=0.49）！在既往多种强化治疗策略难以突破1年PFS瓶颈的PD-L1阴性人群中，芦康沙妥珠单抗联合帕博利珠单抗将mPFS提升至15个月，是标准治疗方案的3倍。从难破一年到跨越15个月，这不仅是数字的跃升，更是重要突破！ OS虽尚未成熟，但HR 为 0.58（95% CI 0.38-0.88），呈现显著改善趋势。PFS 的显著获益，叠加 OS 的向好信号，意味着这套“替代化疗”方案，有望把肿瘤控制优势转化为长期生存红利。如果说OptiTROP-Lung05证明了ADC+IO的巨大潜力，那么OptiTROP-Lung06则将这场变革推向了真正的“攻坚战”，直接探索PD-L1阴性这一俗称“冷肿瘤”人群，头对头帕博利珠单抗联合化疗方案，要知道帕博利珠单抗凭借 KEYNOTE 系列扎实数据一直被认为是晚期NSCLC一线治疗的免疫标杆。图3. OptiROP-Lung06研究mPFS曲线 03 不只是延缓进展，缓解更深、维持更久，牢牢稳住肿瘤，有望实现长生存判断一个治疗方案的成功，不能只看肿瘤缩小比例。能不能把缓解长久维持下去，才是患者真正想要的长期获益。芦康沙妥珠单抗联合免疫在缓解持久性上碾压免疫联合化疗：试验组12 个月 DOR 率 61.7%，相较对照组几乎翻倍（对照组 27.2%）；中位 DOR 13.6个月vs 6.8个月（HR=0.47；95% CI 0.29-0.77）；深度缓解率同样更优：28.8% vs 17.3%。因此这项研究的厉害之处，不单是让更多患者肿瘤缩小；而是一旦获得缓解，就能够长久守住疗效。 PFS、深度缓解、DOR 三大终点相互印证，一套完整的持久抗肿瘤证据链已经成型，为未来 OS 阳性结果埋下巨大伏笔。图4. OptiROP-Lung06研究DoR 04 “替代化疗”≠减疗效！增效同时减毒，具备临床替代化疗硬实力想要替代免疫联合化疗一线标准方案，光疗效显著提升远远不够，安全性也必须过关。化疗带来的重度不良反应，是无数患者治疗路上最大拦路虎。机制上，ADC药物因为其精准递送肿瘤细胞，减少对正常细胞杀伤，使其安全性更高。我们再来看OptiTROP-Lung06 安全性数据确实交出高分答卷，相较免疫联合化疗安全性更优：研究未发现新的安全信号。重度不良反应更少，治疗停药风险更低。 ≥3 级 TEAE：47.6% vs 60.6%；因 TEAE 导致任一研究药物停药比例：5.7% vs 14.2%。患者在摆脱化疗不良反应的同时，能够持续接受有效治疗，持续控制肿瘤。疗效升级+ 毒性降级，让 ADC+IO 拥有了走进真实世界临床的底气。图5. OptiROP-Lung06研究安全性 05 ADC替代化疗联合免疫协同增效，即将成为驱动基因阴性NSCLC一线新标准 ADC联合免疫之所以能打出“替代化疗”的惊艳战绩，核心在于二者天然协同，双重机制合力出击。新一代ADC绝不是简单的“化疗pro”，完美实现了传统化疗“广谱杀伤”到全新精准递送的升级，还能增强抗原呈递，招募T细胞并激活，使冷肿瘤向更具炎症性和浸润性的微环境转变，同时免疫治疗则松开免疫“刹车”，解除肿瘤微环境免疫抑制，进一步放大T细胞应答，细胞毒效应+ 抗肿瘤免疫叠加，实现 1+1＞2 的协同威力，使患者获得更佳生存获益。芦康沙妥珠单抗依托OptiDC™平台独特分子设计，构建起替代化疗的药物基础：优化连接子实现血循环双重稳定、肿瘤内酸性环境 + 溶酶体酶解双重释药；搭载新型拓扑异构酶 I 抑制剂 T030，肿瘤组织载荷暴露更高。T030 兼具膜穿透性，可产生旁观者效应，诱导免疫原性细胞死亡，释放肿瘤抗原，同步发挥细胞毒杀伤与免疫激活作用，实现 1+1>2 的协同抗肿瘤效果，同时降低脱靶毒性。结语肺癌一线的治疗版图，正在被重新改写。很长一段时间里，驱动基因阴性、PD-L1 阴性晚期非鳞 NSCLC 免疫联合化疗是一线治疗唯一选择，临床只能在疗效和化疗毒性之间艰难取舍。OptiTROP-Lung06 Ⅲ 期重磅数据，撕开了新的突破口。头对头击败标准方案，PFS 显著获益，缓解更持久，安全性全面占优。与05研究形成完整证据闭环，芦康沙妥珠单抗联合免疫 “替代化疗” 策略，为驱动基因阴性NSCLC患者带来明确无进展生存获益，期待成熟OS 数据，终将改写驱动基因阴性晚期 NSCLC 一线治疗格局。肺癌“替代化疗”时代，正在加速到来。参考文献 [1]Caicun Zhou.2026 ESMO, LBA66. [2]Garassino MC, Gadgeel S, Speranza G, et al. Pembrolizumab Plus Pemetrexed and Platinum in Nonsquamous Non-Small-Cell Lung Cancer: 5-Year Outcomes From the Phase 3 KEYNOTE-189 Study. J Clin Oncol. 2023 Apr 10;41(11):1992-1998. [3]Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed as first-line therapy for advanced non-squamous non-small-cell lung cancer: 5-year outcomes of the CameL randomized phase 3 study. J Immunother Cancer. 2024 Nov 27;12(11):e009240. [4]Lu S, Wang J, Yu Y, et al. Tislelizumab plus chemotherapy as first-line treatment of locally advanced or metastatic nonsquamous non-small-cell lung cancer (final analysis of RATIONALE-304: a randomized phase III trial). ESMO Open. 2024 Oct;9(10):103728. [5]Yang Y, Wang Z, Fang J, et al. Efficacy and Safety of Sintilimab Plus Pemetrexed and Platinum as First-Line Treatment for Locally Advanced or Metastatic Nonsquamous NSCLC: a Randomized, Double-Blind, Phase 3 Study (Oncology pRogram by InnovENT anti-PD-1-11). J Thorac Oncol. 2020 Oct;15(10):1636-1646. [6]Wang L, Hao X, Hao Y, et al. First-line serplulimab plus chemotherapy with or without HLX04 versus chemotherapy in locally advanced or metastatic non-squamous non-small-cell lung cancer (ASTRUM-002): a randomised, double-blind, multicentre phase 3 trial. Lancet Respir Med. 2026 Feb;14(2):117-128. [7]Hellmann MD, Paz-Ares L, Bernabe Caro R,et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. [8]Paz-Ares L, Ciuleanu TE, Cobo M, et al.First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Feb;22(2):198-211. [9]Johnson ML, Cho BC, Luft A,et al. Durvalumab With or Without Tremelimumab in Combination With Chemotherapy as First-Line Therapy for Metastatic Non-Small-Cell Lung Cancer: The Phase III POSEIDON Study. J Clin Oncol. 2023 Feb 20;41(6):1213-1227. [10]Chen Z, Yang F, Jiang Z, et al.Ivonescimab plus chemotherapy versus tislelizumab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (HARMONi-6): a randomised, double-blind, phase 3 trial. Lancet. 2025 Nov 1;406(10515):2078-2088. [11]Socinski MA, Jotte RM, Cappuzzo F, et al. Atezolizumab for First-Line Treatment of Metastatic Nonsquamous NSCLC. N Engl J Med. 2018 Jun 14;378(24):2288-2301. [12]Herbst RS, Cho BC, Zhou C, et al. Lenvatinib Plus Pembrolizumab, Pemetrexed, and a Platinum as First-Line Therapy for Metastatic Nonsquamous NSCLC: Phase 3 LEAP-006 Study. J Thorac Oncol. 2025 Sep;20(9):1302-1314. [13]Xiong A, Yao W, Zheng W, et al. Sacituzumab tirumotecan plus pembrolizumab versus pembrolizumab in PD-L1-positive advanced non-small-cell lung cancer (OptiTROP-Lung05): interim analysis of a randomised, open-label, phase 3 trial. Lancet. 2026 Jun 27;407(10548):2607-2619.

临床结果ASCO会议免疫疗法抗体药物偶联物临床3期

2026-10-22

·博安生物

Boan Announces First Subject Enrolled in Phase I Clinical Trial of BA1203 (A Masked Anti-PD-1/IL-2 Fusion Protein) in China

Boan Biotech announced today that the first subject has been enrolled in a Phase I clinical trial of BA1203 in China. BA1203 is an investigational anti-PD-1/IL-2 antibody-cytokine prodrug. To the company’s knowledge, it is the world’s only PD-1/IL-2 molecule that combines high activity at the IL-2α receptor with an IL-2 masking design and PD-1-blocking activity. The Phase I clinical trial is a multicenter, open-label study designed to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of BA1203 in patients with advanced solid tumors. Immuno-oncology (IO) therapies, represented by PD-1/PD-L1 inhibitors, have become a cornerstone treatment for malignancies. However, clinical benefit varies across tumor types and patient populations. A significant proportion of patients still experience primary non-response, disease recurrence, or treatment resistance, underscoring the need for new treatment options. IL-2 is a key cytokine that promotes T-cell proliferation and functional recovery. However, traditional IL-2 therapies are limited by a narrow therapeutic window, non-selective activation of peripheral immune cells and the risk of systemic toxicity. Achieving targeted delivery and selective activation of IL-2 within the tumor microenvironment (TME) has become a key focus of next-generation IO therapies. As a next-generation IO drug candidate developed by Boan Biotech, BA1203 combines the mechanisms of action of a PD-1 antibody and an IL-2 cytokine, aiming to achieve immune checkpoint blockade and localized immune activation within the TME simultaneously. Through its IL-2 masking prodrug design, BA1203 is intended to selectively activate IL-2 within the TME while maintaining lower IL-2 activity in peripheral tissues, thereby enhancing local antitumor immunity and reducing the risk of systemic toxicity. The molecule also incorporates a high-affinity, bivalent PD-1-targeting design that strengthens checkpoint blockade and facilitates the precise delivery of IL-2 to PD-1-positive tumor-infiltrating T cells. In addition, BA1203 features a symmetric molecular structure, which helps improve molecular stability and the controllability of the manufacturing process. Preclinical studies have shown that BA1203 demonstrates excellent anti-tumor activity, significantly outperforming existing PD-1/PD-L1 inhibitors across multiple tumor models that showed limited or no response to these agents. In tumor-bearing mouse models, BA1203 demonstrated superior efficacy compared to competitors in the same class and exhibited a favorable safety profile characterized by tumor-dependent activation, with low peripheral toxicity and enhanced local immune activation within tumors. BA1203 also demonstrated a favorable safety and tolerability profile in cynomolgus monkey studies. Jiang Hua, Chairlady and Chief Executive Officer of Boan Biotech, said: “PD-1/IL-2 has become a key focus of next-generation IO drug development worldwide. BA1203’s differentiated design incorporates high-affinity, bivalent PD-1 targeting, a masked IL-2 prodrug and a symmetric molecular structure. These features are intended to enhance local immune responses within tumors while reducing the risk of peripheral toxicity, potentially offering a new approach to improving the efficacy of cancer immunotherapy. We will accelerate BA1203’s clinical development and explore its potential as a monotherapy and in combination regimens across multiple types of solid tumors.” About Boan Biotech Boan Biotech (6955.HK) is a fully-integrated biopharmaceutical company developing, manufacturing, and marketing biologics, with a focus on oncology, autoimmune diseases, ophthalmology, and metabolic diseases. The company’s drug discovery activities revolve around multiple platforms: Human Antibody Transgenic Mouse Technology Platform, Bispecific/Multi-specific/Probody Technology Platform, ADC Technology Platform and Artificial Intelligence/Big Data Application Platform. Boan Biotech operates across the entire value chain of the industry covering antibody discovery, cell line development, upstream and downstream process development, analytical and bio-analytical method development, technology transfer, non-clinical research, clinical research, regulatory affairs and registration, and commercial production. Boan Biotech currently has five products that have been approved for marketing, along with a robust pipeline of proprietary investigational biologics and biosimilars. In addition to China, the company is also developing biopharmaceutical products in overseas markets, including the U.S., Europe, and Japan. With a differentiated portfolio and well-established commercial capabilities, Boan Biotech operates across the industry’s value chain from research and development to manufacturing and commercialization, laying a solid foundation for long-term, high-quality growth in the future.

临床研究基因疗法

2026-10-20

·BioArt

Cell Host & Microbe | 马学磊等团队揭示Akk菌抑制巨噬细胞胞葬作用，增效MSS型结直肠癌抗PD-1治疗

结直肠癌是全球第三大常见恶性肿瘤。免疫检查点阻断疗法虽彻底改变了dMMR/MSI-H型结直肠癌的治疗格局，但约85%的结直肠癌为pMMR/MSS型，肿瘤呈免疫“冷肿瘤”状态，对抗PD-1治疗天然耐药，是临床亟待突破的难点。近年来，肠道菌群被证明深刻影响免疫治疗疗效，Akk菌丰度与抗PD-1应答正相关，但其在MSS型结直肠癌中的作用机制及临床转化价值尚不明确。近日，四川大学华西医院马学磊教授团队在 Cell Host & Microbe 杂志在线发表了题为 Akkermansia muciniphila attenuates macrophage efferocytosis to enhance anti-PD-1 efficacy in microsatellite-stable colorectal cancer 的研究论文。该研究揭示了肠道共生菌嗜黏蛋白阿克曼菌（Akkermansia muciniphila，简称Akk菌）通过抑制肿瘤相关巨噬细胞的胞葬作用（efferocytosis），激活cGAS-STING-I型干扰素通路，重塑肿瘤免疫微环境，从而增效抗PD-1治疗的新机制，并在一项I期临床试验中初步验证了Akk菌联合抗PD-1治疗晚期MSS型结直肠癌的安全性与疗效信号。研究团队首先发现，结直肠癌患者粪便及肿瘤组织中的Akk菌丰度显著降低。在CT26、MC38等多种结直肠癌小鼠模型中，口服Akk菌可显著抑制肿瘤生长。单细胞测序联合流式细胞术分析显示，Akk菌处理显著减少了肿瘤内C1q⁺肿瘤相关巨噬细胞（TAMs）的比例，并下调Gas6、Axl、Mertk等胞葬作用相关基因。功能实验证实，Akk菌处理后TAMs吞噬清除凋亡肿瘤细胞的能力（即胞葬作用）显著下降，导致凋亡肿瘤细胞在肿瘤内蓄积，并伴随HMGB1等损伤相关分子模式（DAMP）释放增加。机制上，研究团队阐明了一条完整的信号轴：Akk菌通过其外膜蛋白Amuc_1100激活巨噬细胞TLR2/NF-κB信号，抑制胞葬作用；凋亡细胞清除受阻后，肿瘤内双链DNA积聚，激活巨噬细胞内的cGAS-STING通路，促进I型干扰素（IFN-β）产生，进而激活效应性CD8⁺ T细胞，将“冷肿瘤”转化为“热肿瘤”。上述信号轴的每一环节均经过阻断与回补实验的验证，因果关系明确。值得注意的是，巴氏灭活的Akk菌及重组Amuc_1100蛋白均可复制上述抗肿瘤效应，提示Akk菌的结构成分（而非上清代谢物）发挥关键作用，为开发安全性更高的灭活菌制剂提供了理论依据。在联合治疗方面，Akk菌与抗PD-1联用在多种MSS型模型中显著优于任一单药，而在高免疫原性的MC38模型中无额外获益，提示该策略对“冷肿瘤”更具针对性；此外，Akk菌还可增效奥沙利铂化疗及放疗，显示其作为广谱治疗佐剂的潜力。基于上述前临床证据，团队开展了一项单臂I期临床研究（NCT06865521），纳入22例晚期MSS型结直肠癌患者，给予巴氏灭活Akk益生菌联合以抗PD-1为基础的抗肿瘤治疗。结果显示，联合方案安全性良好，无4级及以上毒性、无益生菌相关感染；在21例可评估患者中，客观缓解率（ORR）达19%（含1例完全缓解），疾病控制率（DCR）达76%。其中一例经标准化疗及靶向治疗后进展的肺转移患者，在两个治疗周期后即达到影像学完全缓解。免疫监测显示，应答患者治疗后外周血IFN-γ、GZMB⁺及Perforin⁺ CD8⁺ T细胞升高，耗竭型CD8⁺ T细胞减少。综上所述，该研究将巨噬细胞胞葬作用引入肠道菌群调控肿瘤免疫的机制框架，阐明了“Akk菌—巨噬细胞胞葬—cGAS-STING—I型干扰素—CD8⁺ T细胞”这一此前未被认识的完整机制链条，并通过I期临床试验提供了初步的临床转化证据，为占比约85%的MSS型结直肠癌患者克服免疫治疗耐药提供了“菌群干预”新策略。四川大学华西医院马学磊教授为本文最后通讯作者，江雨婷、李光琦、周裕文为本文共同第一作者。原文链接： https://www.cell.com/cell-host-microbe/fulltext/S1931-3128(26)00403-8 制版人：十一学术合作组织（*排名不分先后）战略合作伙伴（*排名不分先后） · 推荐直播 · 转载须知【非原创文章】本文著作权归文章作者所有，欢迎个人转发分享，未经作者的允许禁止转载，作者拥有所有法定权利，违者必究。 BioArt Med Plants 人才招聘点击主页推荐活动关注更多最新活动！

100 项与 Sym-021 相关的药物交易

登录后查看更多信息

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
晚期恶性实体瘤	临床1期	美国	Institut Servier de Medecine Translationnelle SARL	2021-10-15
晚期恶性实体瘤	临床1期	加拿大	Institut Servier de Medecine Translationnelle SARL	2021-10-15
胆管癌	临床1期	美国	Servier Symphogen A/S	2020-10-12
胆管癌	临床1期	加拿大	Servier Symphogen A/S	2020-10-12
胆管癌	临床1期	法国	Servier Symphogen A/S	2020-10-12
胆管癌	临床1期	西班牙	Servier Symphogen A/S	2020-10-12
食管鳞状细胞癌	临床1期	美国	Servier Symphogen A/S	2020-10-12
食管鳞状细胞癌	临床1期	加拿大	Servier Symphogen A/S	2020-10-12
食管鳞状细胞癌	临床1期	法国	Servier Symphogen A/S	2020-10-12
食管鳞状细胞癌	临床1期	西班牙	Servier Symphogen A/S	2020-10-12

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT05162755	临床1期	实体瘤末线 \| 二线 \| 三线	41	Sym025	構遞網鹹膚構窪遞製鹽(廠壓觸製蓋鑰網艱獵蓋) = 鏇繭選鹹淵鬱顧網蓋餘壓憲艱鏇獵選範積構蓋 (構願夢築簾夢選糧廠夢 ) 更多	积极	2024-11-05
				Sym021+Sym025	構遞網鹹膚構窪遞製鹽(廠壓觸製蓋鑰網艱獵蓋) = 鑰鏇糧鬱鑰簾鑰繭範願壓憲艱鏇獵選範積構蓋 (構願夢築簾夢選糧廠夢 ) 更多
NCT03489343 \| NCT03311412 \| NCT03489369 (ESMO2020)	临床1期	转移性肿瘤 \| 晚期恶性实体瘤 \| 淋巴瘤	-	Sym021	構廠醖簾顧鬱窪選蓋獵(窪選淵鹽築網鑰廠築廠) = Sym021, Sym022 and Sym023 alone and Sym021 in combination with either Sym022 or Sym023 were well tolerated with AE profiles typical of immune checkpoint inhibitors 積遞願襯壓遞鏇蓋顧壓 (繭鏇遞醖顧憲築鹽網夢 )	-	2020-09-20
				Sym022
AUA2020	N/A	泌尿生殖系统肿瘤 HLA-I genotypes \| HLA-C genotypes \| KIR ligands ... 更多	51	anti-PD-1 drugs (HLA-A2 supertype)	鑰膚願衊鹹廠醖壓廠鑰(衊顧艱築製壓製鹹餘蓋) = 鬱衊顧積繭餘夢醖構鹹繭鏇艱網齋願襯顧廠鏇 (襯獵蓋鬱糧鹹醖顧壓遞 )	-	2020-04-01
				anti-PD-1 drugs (Patients without HLA-A2 supertype)	鑰膚願衊鹹廠醖壓廠鑰(衊顧艱築製壓製鹹餘蓋) = 網繭簾夢襯鏇鹹壓範遞繭鏇艱網齋願襯顧廠鏇 (襯獵蓋鬱糧鹹醖顧壓遞 )