A Multicenter Open-label, Prospective Study to Evaluate the Efficacy and Safety of SIRT Using Yttrium-90 Glass Microspheres Followed by Durvalumab and Tremelimumab for Treatment of Hepatocellular Carcinoma With Portal Vein Thrombosis

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, being the third leading cause of cancer-related death worldwide, with approximately 745 000 deaths reported annually.
For advanced patients, including patients with tumoral portal vein thrombosis (PVT), most treatment guidelines recommend systemic therapy, either combination immunotherapy (IO) or combination of immunotherapy and anti-angiogenic treatment for first line option.
Results for PVT patients are provided in one trial with a median overall survival of 14.2 months with IO underlying the necessity to improve treatment of PVT patients. Two recent other phase 3 trials also reported positive results for different IO regimen.
Selective internal radiation therapy (SIRT) using yttrium-90 (90Y)-loaded glass microspheres (TheraSphereTM) can be used for patients with early stage to locally advanced HCC including PVT patients without extrahepatic spread (EHS). TheraSphereTM is recognized and is reimbursed in France for PVT patients without EHS, since 2019.Several retrospective studies have shown promising results for PVT patients.
Nowadays use of SIRT in locally advanced HCC is regaining interest based on the results of the randomized DOSISPHERE-01 study including non-operable patients, about 70% with PVT. This randomized Phase II trial using 90Y-loaded microspheres sought was noted the effectiveness of 90Y-loaded microspheres using a personalized dosimetry approach versus a standard dosimetry approach.
The use of a systemic treatment as IO after a locoregional treatment with the strong local debulking effect of SIRT is logical and of interest. Indeed, the most frequent pattern of progression after SIRT is recurrence in an untreated area, including untreated liver or EHS. Patients are then usually referred to IO.
Such kind of therapeutic approach, using SIRT followed by IO has already been evaluated in a phase 2 study using nivolumab after 90Y loaded resin microspheres with promising efficacy without safety deterioration.
The aim of this study is to evaluate SIRT followed by IO used according to their current indications in advanced HCC patient with PVT patients and without EHS.

开始日期2026-01-02

申办/合作机构

Center Eugene Marquis

[+1]

NCT06880523

/ Not yet recruiting临床2期IIT

A Phase II Study of STRIDE (Durvalumab + Tremelimumab) With Lenvatinib Versus STRIDE Alone in Patients With Unresectable Hepatocellular Carcinoma (SLIDE-HCC)

The purpose of this study is to compare the effects on participants' and liver cancer by adding a drug that is used on its own to treat this disease to a combination of two other drugs which is also used to treat liver cancer, compared to the two-drug combination alone.

开始日期2025-09-30

申办/合作机构

Canadian Cancer Trials Group

[+2]

NCT06904170

/ Not yet recruiting临床2/3期IIT

An Integrated Phase II/III Randomized Study Comparing Durvalumab and Tremelimumab +/- Hepatic ArteriaL Infusion Chemotherapy With GEMOX in Hepatocellular Carcinoma With High Tumor burdEn

Liver cancer is a highly lethal malignancy and has become increasingly important in western countries. The management of liver cancer is complex. In advanced disease, two combinations of immunotherapies are recommanded as first line (atezolizumab-bevacizumab or durvalumab-tremelimumab). Results in patients with high tumor burden (Portal vein thrombosis Vp3 or Vp4, or tumoral liver involvement >50%) are less impressive. Innovative combinations are necessary to improve the outcome of patients.
Recently, control trials conducted in Asia highlighted the benefit of hepatic arterial infusion chemotherapy, especially in patients with high tumor burden. Studies including a limited number of patients shown that the combination seems feasible.
ALICE is a randomized multicentric Phase II/Phase III trial conducted in French medical centers, evaluating the efficacy and safety of durvalumab+tremelimumab with or without Hepatic Arterial Infusion Chemotherapy of the GEMOX regimen (gemcitabine + oxaliplatin), in patients with high tumor burden.
Oxaliplatin induce immunogenic cell death, and gemcitabin deplete regulatory immune cells. The GEMOX regimen thus has the potential for a synergic effect with immunotherapy in HCC.
The trial will provide an innovative treatment to patients with no alternative for locoregional treatment, and with limited results with actual systemic treatments. It will also be the first trial of Hepatic Arterial infusion for such patients in the western population.

开始日期2025-09-01

申办/合作机构

UNICANCER

[+1]

100 项与曲美木单抗相关的临床结果

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100 项与曲美木单抗相关的转化医学

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100 项与曲美木单抗相关的专利（医药）

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662

项与曲美木单抗相关的文献（医药）

2025-12-31·mAbs

Engineered ipilimumab variants that bind human and mouse CTLA-4

Article

作者: Barman, Ishita ; Lee, Peter S. ; Diong, SJ ; Bee, Christine ; Rajpal, Arvind ; Kumar, Anusha ; West, Sean M. ; Chau, Bryant ; Strop, Pavel ; Robison, Brett ; Chang, Olin ; Korman, Alan J. ; Moon, Thomas M.

Testing of candidate monoclonal antibody therapeutics in preclinical models is an essential step in drug development. Identification of antibody therapeutic candidates that bind their human targets and cross-react to mouse orthologs is often challenging, especially for targets with low sequence homology. In such cases, surrogate antibodies that bind mouse orthologs must be used. The antibody 9D9, which binds mouse CTLA-4, is a commonly used surrogate for CTLA-4 checkpoint blockade studies in mouse cancer models. In this work, we reveal that 9D9 has significant biophysical dissimilarities to therapeutic CTLA-4 antibodies. The 9D9-mCTLA4 complex crystal structure was determined and shows that the surrogate antibody binds an epitope distinct from ipilimumab and tremelimumab. In addition, while ipilimumab has pH-independent binding to hCTLA-4, 9D9 loses binding to mCTLA-4 at physiologically relevant acidic pH ranges. We used phage and yeast display to engineer ipilimumab to bind mouse CTLA-4 with single-digit nM affinity from an initial state with no apparent binding. The engineered variants showed pH-independent and cross-reactive binding to both mouse and human CTLA-4. Crystal structures of a variant in complex with both mouse and human CTLA-4 confirmed that it targets an equivalent epitope as ipilimumab. These cross-reactive ipilimumab variants may facilitate improved translatability and future mechanism-of-action studies for anti-CTLA-4 targeting in murine models.

2025-12-01·Journal of Gastrointestinal Cancer

The Efficacy and Safety of Durvalumab and Tremelimumab with Concomitant Treatment for MSS/pMMR Metastatic Colorectal Cancer: A Single Arm Meta-Analysis

Article

作者: Zhang, Danning ; Chen, Tianyu

OBJECTIVES:

To address the issue that most microsatellite-stable (MSS) and proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) patients have minimal response to immunotherapy, this meta-analysis evaluated the efficacy and safety of durvalumab and tremelimumab with concomitant treatment in treating MSS/pMMR metastatic colorectal cancer.

METHODS:

All included trials were prospective studies with a median patient age of 63 years, of which 94.2% were MSS/pMMR mCRC patients, with a male to female ratio of 1.5:1. Based on durvalumab and tremelimumab treatment, one study performed surgical resection on resectable cases, while the other four studies performed radiotherapy or chemotherapy on unresectable cases. Analyses include objective response rate (ORR).etc. for drug activity, overall survival (OS) and progression-free survival (PFS) for therapeutic efficacy, and adverse events (AEs) for safety. The risk of bias was assessed by sensitivity analysis.

RESULTS:

5 studies involving 228 patients were included in this meta-analysis. The pooled estimates showed a median OS of 9.26 months, median PFS of 2.53 months, partial response (PR) of 13.6%, stable disease (SD) of 32.8%, ORR of 12.5% and disease control rate (DCR) of 65.4%. AEs were generally low, with pruritus (27.5%), diarrhea (28.8%), and fatigue (53.9%) being the most common, while other AEs occurred at less frequencies.

CONCLUSIONS:

Durvalumab and tremelimumab with concomitant treatment for MSS/pMMR mCRC patients is relatively effective and safe, which is helpful in addressing the problem of mCRC with MSS/pMMR that has minimal response to immunotherapy.

2025-12-01·Journal of Gastrointestinal Cancer

Neutrophil-to-Lymphocyte Ratio (NLR) as a Predictive Biomarker in Advanced Hepatocellular Carcinoma Treated with First-Line Immunotherapy

Article

作者: Felismino, Tiago ; Martins, Luanna ; Brito, Angelo ; Maccali, Claudia ; Barroso, Matheus ; Carvalho, Daniela ; Coimbra, Felipe

PURPOSE:

Hepatocellular carcinoma (HCC) is a globally prevalent malignancy with high mortality and limited predictive biomarkers. The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammation marker, has been proposed as a prognostic tool. This study aimed to evaluate the association between baseline NLR and clinical outcomes in patients with advanced HCC treated with first-line immunotherapy.

METHODS:

We conducted a retrospective analysis of 58 consecutive patients with advanced HCC treated with atezolizumab plus bevacizumab or durvalumab plus tremelimumab at a Latin American cancer center between July 2020 and March 2025. Baseline NLR was calculated from pretreatment blood counts and dichotomized using a cut-off of 4. Progression-free survival (PFS) and overall survival (OS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox regression models were applied to assess prognostic and predictive factors. The association between NLR and disease control rate (DCR) was evaluated using logistic regression.

RESULTS:

Among 58 patients, 15 (28.8%) had NLR ≥ 4. Median PFS was significantly shorter in patients with NLR ≥ 4 compared to those with NLR < 4 (2.3 vs. 8.2 months; p < 0.001). In multivariable analysis, NLR ≥ 4 remained independently associated with inferior PFS (HR 3.90; 95% CI, 1.83-8.33; p < 0.001). NLR was not associated with OS. Patients with NLR ≥ 4 had markedly lower odds of achieving disease control (OR 0.04; 95% CI, 0.002-0.28; p = 0.005).

CONCLUSION:

Baseline NLR ≥ 4 is associated with inferior PFS and reduced DCR in patients with advanced HCC receiving immunotherapy. NLR may serve as a cost-effective predictive biomarker to inform immunotherapy strategy.

512

项与曲美木单抗相关的新闻（医药）

2025-09-02

·ioncology

Hepatol Int丨阿替利珠单抗联合贝伐珠单抗治疗uHCC 3年OS数据公布，符合特定标准者超30%

点击蓝字关注我们肝细胞癌（HCC）仍是癌症相关死亡的主要原因之一。尽管阿替利珠单抗/贝伐珠单抗联合方案在IMbrave150临床试验中展现出显著疗效，但由于随访时间有限，其长期结局，尤其是3年总生存期（OS）尚未明确。目前已有关于曲美木单抗/度伐利尤单抗联合方案长期结局的报道，因此亟需获取阿替利珠单抗/贝伐珠单抗联合方案的可比数据。近日，一项发表于Hepatology International的研究阐明了接受阿替利珠单抗联合贝伐珠单抗治疗的不可切除肝细胞癌（uHCC）患者的3年OS。文章图形摘要该回顾性多中心研究纳入了接受阿替利珠单抗/贝伐珠单抗联合治疗的uHCC患者。在参与研究机构治疗的506例患者中，仅纳入2020年10月至2022年1月期间启动治疗的患者。研究收集了患者全面的临床、实验室及影像学数据，并对患者进行随访直至2025年3月。该研究共分析了257例患者，中位随访时间为48.23个月（范围：36.23-53.60个月）。患者的2年总生存率和3年总生存率分别为39.2%和25.3%。在符合IMbrave150临床试验入组标准的患者中，3年总生存率为31.6%。多因素回归分析显示，基线甲胎蛋白（AFP）水平＞116 ng/mL（OR=为0.41；95%CI：0.20-0.84；P=0.015）以及改良白蛋白-胆红素分级（modified albumin-bilirubin grade）为1-2a级（OR=2.50；95%CI：1.18-5.32；P=0.017）是与3年OS相关的显著影响因素。在真实临床场景中，接受阿替利珠单抗联合贝伐珠单抗治疗的uHCC患者，其3年总生存率为25.3%；而在符合IMbrave150临床试验入组标准的患者中，这一比例升至31.6%。该生存结局数据凸显了阿替利珠单抗/贝伐珠单抗联合方案在改善uHCC患者长期预后以及指导一线治疗决策方面的临床价值。参考文献：Ohara M, Suda G, Kohya R, et al. Three-year overall survival in unresectable hepatocellular carcinoma treated with atezolizumab plus bevacizumab. Hepatol Int. Published online August 28, 2025. doi:10.1007/s12072-025-10875-7 （来源：《国际肝病》编辑部）声明凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。

2025-09-02

·Biotech前瞻

康方依沃西单抗丨打完K药，剑指D药，胆道肿瘤二期惊艳，三期入组完成

点击蓝字关注我们本期看点恶性胆道系统肿瘤（Biliary tract carcinoma，BTC）较为少见，但诊断和治疗较为棘手，有着“小癌王”之称。既往系统治疗主要以化疗为主，随着TOPAZ-1、KeyNote966两项全球大III期获得阳性结果，免疫联合化疗成为BTC系统治疗的新一线标准。康方生物的依沃西单抗（AK112，PD-1/VEGF双抗）于2024年8月开展头对头度伐利尤单抗+化疗的随机III期研究。2025年9月2日宣布完成入组，速度可谓是快。这是继依沃西单抗联合化疗对比帕博利珠单抗联合化疗一线治疗转移性鳞状非小细胞肺癌的随机3期研究后再次硬刚MNC旗下重磅ICIs，足见康方生物对于依沃西单抗的信心十足。本期内容 01 依沃西单抗丨BTC一线丨三期 02 依沃西单抗丨BTC一线丨Ib/II期 03 II期数据同比，是否仍具优势？ 04 总结与展望【01 依沃西单抗丨BTC一线丨三期】日前，康方生物（9926.HK）独立自主研发的PD-1/VEGF双特异性抗体依沃西联合方案，对比度伐利尤单抗（PD-L1）联合方案，用于一线治疗晚期胆道恶性肿瘤（BTC）的随机、对照、多中心、注册性III期临床研究（AK112-309/HARMONi-GI1）完成患者入组。康方生物的依沃西单抗（AK112，PD-1/VEGF双抗）在肝胆领域动作频繁，先后在肝癌领域尝试双抗联双抗和双抗联合靶向加介入的注册研究：康方PD-1/CTLA-4双抗+PD-1/VEGF双抗，“剑指”HCC、康方双抗开展肝癌三期，靶+免+介入三联疗法重塑HCC治疗格局。而在已经有TOPAZ-1、KeyNote966两项全球大III期验证成功的晚期胆道肿瘤（BTC）一线，2024年8月25日，康方生物开展了依沃西单抗（AK112）联合化疗对比度伐利尤单抗联合化疗一线治疗晚期胆道癌的头对头III期临床试验，主要研究者为哈尔滨医科大学附属肿瘤医院的郑桐森教授和复旦大学附属中山医院的周俭教授。共计入组患者人数为682例。 cited by：药物临床试验登记与信息公示平台该项研究的开启，也即意味着继依沃西单抗（AK112，PD-1/VEGF双抗）联合化疗对比帕博利珠单抗联合化疗一线治疗转移性鳞状非小细胞肺癌的随机3期研究后，依沃西单抗再次挑战MNC的重磅ICIs，此次BTC领域正面硬刚阿斯利康的度伐利尤单抗，足见康方生物对于依沃西单抗的信心十足。 cited by：药物临床试验登记与信息公示平台 2024年ASCO大会中，浙江省肿瘤医院应杰儿团队牵头的，采用康方生物自主研发的依沃西单抗（PD-1/VEGF双抗）联合标准化疗一线治疗胆道恶性肿瘤（BTC）的研究，整体疗效数据较为优异，尤其是胆囊癌患者。 02 依沃西单抗丨BTC一线丨Ib/II期 NCT05214482是一项开放、多中心、Ib/II期研究，旨在探讨依沃西单抗（PD-1/VEGF双抗）联合化疗±AK117(CD47单抗) 的安全性和有效性。本次报告中，该研究共入组22例BTC患者，均采用依沃西单抗联合吉西他滨和顺铂治疗，中位随访时间13.8个月，疗效和安全性如下： ≥3级TRAE占86.4%，但无治疗导致的停药或死亡。 ORR达63.6%(14/22)，DCR为100%。 mPFS达8.5个月(95%CI, 6.8-10.5)，mOS达16.8个月(95%CI, 9.2-NE)。在既往的Keynote-966研究中，第一次中期分析时，中位随访时间13.6个月，帕博利珠单抗联合化疗组的mPFS为6.5个月(95%CI, 5.7-6.9)，ORR为29%。而在最终分析时，mOS报出为12.7个月(95%CI, 11.5-13.8)。在TOPAZ-1研究中，中位随访时间16.8个月时，度伐利尤联合化疗组的mOS为12.8个月(95%CI, 11.1-14.0)，mPFS达7.2个月(95%CI, 6.7-17.4)，ORR为26.7%。综上数据，我们粗看无论是ORR，还是PFS和OS，似乎依沃西单抗都极具潜力。但这是II期小样本研究数据，即使我们尽量对比相近的随访时间数据，和大III期研究的数据非头对头比较的可参考性也极其有限。 03 II期数据同比，是否仍具优势？事实上，在TOPAZ-1开展前，阿斯利康也曾发布过II期探索结果，NCT03046862研究评估了化疗联合度伐利尤±曲美木单抗在BTC 1L治疗中的安全性和有效性，该研究中度伐利尤单抗联合吉西他滨和顺铂的治疗组共纳入45例患者，中位随访时间11.3个月，疗效数据如下： ORR高达73.4%(60.5-86.3)，DCR为100%。 mPFS为11.0个月(95%CI, 7.0-15.0)，mOS为18.1个月(95%CI, 11.3-24.9)。该研究单从数值上比较，丝毫不逊于依沃西单抗当前的II期数据。当然，该研究的入组人群为韩国人，且仅为单中心研究，从基线看患者ECOG评分为0的占比也更高。除此之外，国内一项单中心研究（ChiCTR2100044476）报告了多个PD-1单抗联合仑伐替尼治疗初始不可切除BTC的数据，该研究共纳入38例患者，ORR仅42.1%，DCR为76.3%，由此可见，既往PD-1单抗联合或不联合抗血管靶向药在BTC 1L治疗的II期数据差异极大，可参考程度也很有限。那么，基于依沃西单抗本次报道的数据自身比较，是否能客观的看出一些信号呢？依沃西单抗亚组分析，胆囊癌优势明显从Keynote-966和TOPAZ-1的亚组分析中，我们可以明确看到，免疫治疗的加入主要对肝内胆管癌起到作用，而在肝外胆管癌和胆囊癌中并无明显获益优势。但本次康方报出的依沃西单抗研究中，专门提到胆囊癌亚组，ORR高达77.8%，mOS为16.8个月。虽然当前入组数量较少，但是否该信号提示，PD-1/VEGF双抗有望在此类人群中有重要突破？这一特点是否和康方另一款已上市双抗——卡度尼利单抗（PD-1/CTLA-4双抗）有异曲同工？前期无论卡度尼利单抗在宫颈癌适应症中数据，还是2024AACR最新报出的胃癌III期数据，均显示其无论PD-L1的表达，可全人群获益，这相较于既往的PD-1单抗而言，PD-L1低表达人群仍可显著获益是一大亮点。那么如今依沃西单抗是否也能凭借其独有的双抗结构优势，为既往单免不能获益的人群带来新的希望呢？该优势究竟来源于靶免联合的协同作用特点，还是双抗独特的结构作用，更多分析我们拭目以待。 04 总结与展望随着依沃西在越来越多肿瘤适应症迭代PD-1疗法或VEGF疗法的推进，依沃西的全球市场潜力也越发凸显。参考文献1. Annals of Oncology (2024) 35 (suppl_1): S119-S161. 10.1016/annonc/annonc14812 . Jieer Ying, et al. 2024 ASCO, poster4095.3. Kelley RK, et al. Lancet. 2023, 401(10391):1853-1865. 4. Oh DY, et al. NEJM Evid. 2022, 1(8):EVIDoa2200015. 5. Oh DY, et al. Lancet Gastroenterol Hepatol. 2022, 7(6):522-532. 6. Zhang Q, et al. Front Oncol. 2021, 11:751391. 行文不易，欢迎关注，为中国的Biotech行业保驾护航，也是人生幸事。科普新号，用浅显易懂的语言，惠及广泛人群。 ★

临床3期引进/卖出ASCO会议临床1期临床2期

2025-09-02

·Biotech前瞻

O+Y后线治疗胆囊癌优势明显，PD-1/VEGF双抗同样验证

本期看点胆道恶性肿瘤恶性胆道系统肿瘤（Biliary tract carcinoma，BTC）较为少见，但诊断和治疗较为棘手，有着“小癌王”之称。既往系统治疗主要以化疗为主，随着TOPAZ-1、KeyNote966两项全球大III期获得阳性结果，免疫联合化疗成为BTC系统治疗的新一线标准。而随着对BTC分子特征的深入了解，针对不同人群和亚型BTC病人制订更为明确的个体化治疗方案，是未来免疫治疗的关键。本文就2024ESMO GI大会上公布的O+Y后线治疗BTC及2024 ASCO大会上公布的PD-1/VEGF双抗联合化疗一线治疗BTC的两项研究进行深入解读。 2024 ESMO GI 2024年欧洲肿瘤内科学会(ESMO)胃肠道癌症大会于2024年6月26-29日在德国慕尼黑举行，会议由欧洲肿瘤内科学会(ESMO)主办，ESMO胃肠道肿瘤大会将成为展示胃肠道肿瘤学领域有影响力的新数据的平台，科学会议将辅以高质量的教育会议和良好的交流机会。 cited by：2024 ESMO GI 官网比较关注有着“小癌王”之称的胆道系统肿瘤( biliary tract carcinoma，BTC) 治疗最新进展，BTC主要包括胆囊癌( gallbladder cancers，GBC) 和胆管癌( cholangiocarcinoma，CCA) 。胆道肿瘤占所有肿瘤的＜1%，约占所有消化系肿瘤的3%。主要发生在70岁左右，男性多与女性（1.2-1.5:1）。2024年ESMO GI大会上，Oliver Klein团队汇报了一项纳武利尤单抗和伊匹木单抗（O+Y）联合治疗晚期ICC和GBC的MoST-CIRCUIT（NCT04969887）研究。 PD-1/CTLA-4双免疫，胆囊癌优势明显背景抗PD-1/PD-L1阻断联合化疗已经成为晚期胆道肿瘤（BTC）的一线标准治疗。在既往的两项试验（CA209-538, SWOG1609）中，使用纳武利尤单抗和伊匹木单抗的抗PD-1/CTLA-4联合阻断在肝内胆管癌（iCCA）和胆囊癌（GB）患者中显示出令人鼓舞的活性。MoST-CIRCUIT（NCT04969887）进一步评估了在这类患者群体中联合检查点阻断的效果。方法在澳大利亚的14个中心，共招募了60名晚期肝内胆管癌或胆囊癌患者。患者接受Nivo 3mg/kg和Ipi 1mg/kg，每3周一次，共4剂，随后每4周接受Nivo 480mg，持续96周，或直至疾病进展或出现不可接受的毒性。每12周评估一次反应（RECIST 1.1）。主要终点是客观反应率（ORR）和6个月无进展生存期。42名患者通过进行了肿瘤基因组分析。结果共招募了37名iCCA和23名GB患者，其中78%（47名）的患者曾接受过一线治疗，包括12名接受度伐利尤单抗治疗的患者。整体人群的ORR为15%，iCCA和GB患者分别为6%和32%，中位反应持续时间为4.2个月（范围1-10.4）。6个月PFS为22.6%，中位OS为6.7个月。只有一名接受度伐利尤单抗一线化疗联合免疫治疗的患者获得了反应。所有参与者的肿瘤均为微卫星稳定，中位TMB为3.75/MB（范围0-12）。TMB与反应无关（Wilcoxon p=0.81）。28%（17名）的患者经历了3/4级免疫相关不良事件。结论在迄今为止接受联合抗PD-1/CTLA-4阻断治疗的最大BTC队列中，疗效有限。然而，在GB患者中观察到了令人鼓舞的活性，这与最近发现的这一BTC亚型为免疫细胞最丰富的亚型一致。只有一名在一线化疗免疫治疗中使用度伐利尤单抗进展的患者对治疗有反应。在BTC中进一步评估使用检查点阻断的免疫治疗应该集中在GB患者上。无独有偶，2024年ASCO大会中，康方生物自主研发的依沃西单抗（PD-1/VEGF双抗）联合标准化疗一线治疗胆道恶性肿瘤（BTC）整体疗效数据较为优异，尤其是胆囊癌患者。依沃西单抗联合化疗治疗恶性胆道肿瘤，疗效如何？ NCT05214482是一项开放、多中心、Ib/II期研究，旨在探讨依沃西单抗（PD-1/VEGF双抗）联合化疗±AK117(CD47单抗) 的安全性和有效性。本次报告中，该研究共入组22例BTC患者，均采用依沃西单抗联合吉西他滨和顺铂治疗，中位随访时间13.8个月，疗效和安全性如下： ≥3级TRAE占86.4%，但无治疗导致的停药或死亡。 ORR达63.6%(14/22)，DCR为100%。 mPFS达8.5个月(95%CI, 6.8-10.5)，mOS达16.8个月(95%CI, 9.2-NE)。在既往的Keynote-966研究中，第一次中期分析时，中位随访时间13.6个月，帕博利珠单抗联合化疗组的mPFS为6.5个月(95%CI, 5.7-6.9)，ORR为29%。而在最终分析时，mOS报出为12.7个月(95%CI, 11.5-13.8)。在TOPAZ-1研究中，中位随访时间16.8个月时，度伐利尤联合化疗组的mOS为12.8个月(95%CI, 11.1-14.0)，mPFS达7.2个月(95%CI, 6.7-17.4)，ORR为26.7%。综上数据，我们粗看无论是ORR，还是PFS和OS，似乎依沃西单抗都极具潜力。但这是II期小样本研究数据，即使我们尽量对比相近的随访时间数据，和大III期研究的数据非头对头比较的可参考性也极其有限。 II期数据同比，是否仍具优势？事实上，在TOPAZ-1开展前，阿斯利康也曾发布过II期探索结果，NCT03046862研究评估了化疗联合度伐利尤±曲美木单抗在BTC 1L治疗中的安全性和有效性，该研究中度伐利尤单抗联合吉西他滨和顺铂的治疗组共纳入45例患者，中位随访时间11.3个月，疗效数据如下： ORR高达73.4%(60.5-86.3)，DCR为100%。 mPFS为11.0个月(95%CI, 7.0-15.0)，mOS为18.1个月(95%CI, 11.3-24.9)。该研究单从数值上比较，丝毫不逊于依沃西单抗当前的II期数据。当然，该研究的入组人群为韩国人，且仅为单中心研究，从基线看患者ECOG评分为0的占比也更高。除此之外，国内一项单中心研究（ChiCTR2100044476）报告了多个PD-1单抗联合仑伐替尼治疗初始不可切除BTC的数据，该研究共纳入38例患者，ORR仅42.1%，DCR为76.3%，由此可见，既往PD-1单抗联合或不联合抗血管靶向药在BTC 1L治疗的II期数据差异极大，可参考程度也很有限。那么，基于依沃西单抗本次报道的数据自身比较，是否能客观的看出一些信号呢？依沃西单抗亚组分析，胆囊癌优势明显从Keynote-966和TOPAZ-1的亚组分析中，我们可以明确看到，免疫治疗的加入主要对肝内胆管癌起到作用，而在肝外胆管癌和胆囊癌中并无明显获益优势。但本次康方报出的依沃西单抗研究中，专门提到胆囊癌亚组，ORR高达77.8%，mOS为16.8个月。虽然当前入组数量较少，但是否该信号提示，PD-1/VEGF双抗有望在此类人群中有重要突破？这一特点是否和康方另一款已上市双抗——卡度尼利单抗（PD-1/CTLA-4双抗）有异曲同工？前期无论卡度尼利单抗在宫颈癌适应症中数据，还是2024AACR最新报出的胃癌III期数据，均显示其无论PD-L1的表达，可全人群获益，这相较于既往的PD-1单抗而言，PD-L1低表达人群仍可显著获益是一大亮点。那么如今依沃西单抗是否也能凭借其独有的双抗结构优势，为既往单免不能获益的人群带来新的希望呢？该优势究竟来源于靶免联合的协同作用特点，还是双抗独特的结构作用，更多分析我们拭目以待。参考文献 1. Annals of Oncology (2024) 35 (suppl_1): S119-S161. 10.1016/annonc/annonc1481 2. Jieer Ying, et al. 2024 ASCO, poster4095. 3. Kelley RK, et al. Lancet. 2023, 401(10391):1853-1865. 4. Oh DY, et al. NEJM Evid. 2022, 1(8):EVIDoa2200015. 5. Oh DY, et al. Lancet Gastroenterol Hepatol. 2022, 7(6):522-532. 6. Zhang Q, et al. Front Oncol. 2021, 11:751391. 行文不易，欢迎关注，为中国的Biotech行业保驾护航，也是人生幸事。科普新号，用浅显易懂的语言，惠及广泛人群。

ASCO会议临床结果引进/卖出临床3期免疫疗法

100 项与曲美木单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D06657	曲美木单抗	-	DB11771

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
肝细胞癌	加拿大	AstraZeneca Canada, Inc.	2023-08-31
晚期肝细胞癌	欧盟	AstraZeneca AB	2023-02-20
晚期肝细胞癌	冰岛	AstraZeneca AB	2023-02-20
晚期肝细胞癌	列支敦士登	AstraZeneca AB	2023-02-20
晚期肝细胞癌	挪威	AstraZeneca AB	2023-02-20
转移性非小细胞肺癌	欧盟	AstraZeneca AB	2023-02-20
转移性非小细胞肺癌	冰岛	AstraZeneca AB	2023-02-20
转移性非小细胞肺癌	列支敦士登	AstraZeneca AB	2023-02-20
转移性非小细胞肺癌	挪威	AstraZeneca AB	2023-02-20
晚期非小细胞肺癌	日本	AstraZeneca KK	2022-12-23
非小细胞肺癌	美国	AstraZeneca AB	2022-11-10
不可切除的肝细胞癌	美国	AstraZeneca AB	2022-10-21

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
非肌层浸润性膀胱肿瘤	临床3期	美国	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	日本	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	阿根廷	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	奥地利	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	巴西	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	加拿大	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	智利	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	法国	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	德国	AstraZeneca PLC	2021-08-05
非肌层浸润性膀胱肿瘤	临床3期	希腊	AstraZeneca PLC	2021-08-05

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT03518606 (MOVIE, Pubmed \| Breast)	临床2期	晚期乳腺癌 ER Negative \| PR Negative \| HER2 Negative	30	Tremelimumab plus Durvalumab combined to metronomic oral Vinorelbine	鑰構鏇餘範築淵鏇獵鏇(選廠壓夢遞蓋鹽網艱憲) = 壓構襯網憲鏇餘築襯齋窪鏇鑰憲鬱簾襯糧製鏇 (廠範鹹衊鏇醖鏇齋醖憲, 5.5 ~ 29.8) 更多	不佳	2025-10-01
NCT03638141 (CTgov)	临床2期	肝细胞癌	21	Tremelimumab+Durvalumab	襯壓蓋艱獵膚鹽鹽築網 = 獵鏇窪願選鬱積網襯範夢觸鏇鑰網鑰鬱餘醖觸 (鹽簾糧膚獵廠鑰艱醖鹽, 積鹹壓膚蓋夢衊衊製鹹 ~ 餘夢觸鹹膚艱淵鏇鹽選) 更多	-	2025-08-17
NCT03703297 (ADRIATIC, CTgov)	临床3期	局限期小细胞肺癌	730	Durvalumab (Durvalumab)	觸壓鬱鹹餘壓構憲窪糧(範獵選艱鹽鏇襯鑰築壓) = 憲鹽鏇壓餘繭積選繭構築獵壓糧遞衊鹹鑰淵築 (夢齋觸膚醖繭顧膚築鏇, 願獵醖製夢範構齋範願 ~ 築襯夢選窪繭廠觸衊鹹) 更多	-	2025-08-01
				placebo (Placebo)	觸壓鬱鹹餘壓構憲窪糧(範獵選艱鹽鏇襯鑰築壓) = 窪獵顧鑰衊襯壓窪襯衊築獵壓糧遞衊鹹鑰淵築 (夢齋觸膚醖繭顧膚築鏇, 鬱範願鹽獵艱繭醖範構 ~ 醖遞願鏇醖鬱艱網齋選) 更多
HIMALAYA Trial (ESMO_GI2025)	N/A	-	233	Durvalumab+Tremelimumab	糧襯蓋淵廠顧鬱衊鹽積(顧鬱鹽選夢積壓鑰夢艱) = 繭選鹹鏇願窪鹽積鑰選積艱鹽襯蓋構觸構觸鏇 (鬱製壓鏇餘鏇遞網糧憲, 43.2 ~ 73.9) 更多	积极	2025-07-03
				Durvalumab	壓糧遞憲蓋糧餘襯蓋網(構蓋醖艱膚網衊範簾積) = 範鬱鹹廠選願簾餘衊網衊憲網遞顧醖衊鏇艱繭 (繭膚廠壓鑰獵鑰餘鏇齋, 8.0 ~ NR) 更多
NCT02815995 (CTgov)	临床2期	卡波西肉瘤 \| 晚期肉瘤	57	Tremelimumab+Durvalumab (Adipocytic Tumors Group)	廠遞選網觸鬱鑰艱衊壓 = 糧願艱鑰窪襯獵淵壓範鬱網選蓋蓋鬱鹽遞齋膚 (獵簾窪廠糧醖顧齋艱網, 糧衊遞鏇顧願餘襯鏇築 ~ 憲憲醖壓網窪餘襯範襯) 更多	-	2025-06-12
				Tremelimumab+Durvalumab (Vascular Tumors Group)	廠遞選網觸鬱鑰艱衊壓 = 襯簾餘艱衊壓繭淵遞鬱鬱網選蓋蓋鬱鹽遞齋膚 (獵簾窪廠糧醖顧齋艱網, 憲範網構憲艱艱糧築淵 ~ 網鑰膚糧築鬱廠鹹壓觸) 更多
NCT02821754 (2019-002767-98, Pubmed \| Gut)	临床2期	肝细胞癌 interferon responses \| antigen presentation \| ICOS ... 更多	28	Tremelimumab plus Durvalumab	範憲築鏇糧憲廠構鑰衊(鏇壓簾觸膚醖醖齋網積) = 遞鹹網獵願獵鬱鑰顧夢衊鹹壓餘夢膚選齋鏇觸 (鹹衊襯夢蓋醖憲餘製淵 )	-	2025-06-01
NCT05844046 (AIO-MONTBLANC, ASCO2025)	临床2期	不可切除的肝细胞癌一线 Child-Pugh A \| AFP ≥400 ng/mL	70	Durvalumab + Tremelimumab	廠構顧選觸顧範蓋築鹽(糧鹹蓋獵範鑰夢鬱網積) = 獵網醖夢願齋觸鹽糧築築糧繭積觸糧繭蓋襯鹽 (糧範憲壓積餘憲衊選構 ) 更多	积极	2025-05-30
ACTRN12617001325392 (BCT1703 DIAmOND, ESMO_BC 12025 \| ESMO_BC 22025) 人工标引	临床2期	晚期 HER2 阳性乳腺癌	68	Total	蓋範淵積艱襯壓網範網(淵鑰鏇積製淵選積鏇餘) = 構鑰積選製鏇顧鏇膚範簾壓憲艱餘簾鑰壓繭憲 (鬱艱鬱淵淵選憲餘繭獵 ) 更多	积极	2025-05-16
				tremelimumabtremelimumab 75mg with durvalumab 1500mg Q4Wdurvalumab 1500mg Q4W and Trastuzumab 2mg/kg Q1W for 12 weeks with ongoing Q3W durvalumab 1120mgTrastuzumab 2mg/kg Q1W for 12 weeks with ongoing Q3W durvalumab 1120mg and Trastuzumab 6mg/kg (C1, estrogen receptor (ER)-positive (≥1%))	蓋範淵積艱襯壓網範網(淵鑰鏇積製淵選積鏇餘) = 遞鹹壓獵選膚願遞膚築簾壓憲艱餘簾鑰壓繭憲 (鬱艱鬱淵淵選憲餘繭獵 ) 更多
NCT03164616 (POSEIDON, ESMO_ELCC2025)	临床3期	转移性非小细胞肺癌一线 EGFR/ALK wild-type	175	Durvalumab + Tremelimumab + Chemotherapy	繭鏇淵窪顧糧淵衊餘鹽(醖構製襯築觸窪衊積簾) = D+T+CT demonstrated statistically significant improvements in both progression-free survival (PFS; HR 0.72; 95% CI 0.60-0.86; p = 0.0003) and overall survival (OS; HR 0.77; 95% CI 0.65-0.92; p = 0.0030) vs CT alone, leading to approvals for this regimen. D+CT significantly improved PFS vs CT (0.74; 95% CI 0.62-0.89; p = 0.0009), with a positive trend for OS improvement (HR 0.86; 95% CI 0.72-1.02; p = 0.0758) 壓選遞鑰壓糧範齋顧獵 (糧鏇廠獵製積壓鬱齋淵 ) 更多	积极	2025-03-26
				Durvalumab + Chemotherapy
NCT02879162 (CTgov)	临床2期	晚期癌症	140	Tremelimumab+Durvalumab	鏇製淵願製淵齋鹽構願(遞蓋餘鹹蓋繭廠顧夢構) = 構築憲淵廠醖壓蓋壓鏇憲繭簾衊窪簾鏇餘繭選 (積糧廠鬱襯願鬱衊淵衊, 衊襯淵壓構築鏇選餘願 ~ 網襯鹹醖襯鹽襯觸醖築) 更多	-	2025-02-17