Eligible participants with limited stage-small cell lung cancer (LS-SCLC) will be enrolled after completion of chemotherapy and radiation. Participants will be randomized to either tarlatamab in combination with durvalumab or durvalumab alone as consolidation therapy. Treatment will continue until disease progression, unacceptable side effects or withdrawal of consent.
Tarlatamab is a targeted cancer treatment. It works by acting as a matchmaker between the immune system's T-cells and the cancer cells, forcing them to come together so the T-cells can attack the cancer.
Image testing will be done standardly during treatment. These tests show whether the cancer has progressed and if further treatment may be needed.
The purpose of this trial is to evaluate how well the treatment works (how long before your cancer comes back and how long you live).

开始日期2027-01-01

申办/合作机构

Amgen, Inc.

NCT07247786

/ Not yet recruiting临床2期

Phase II Randomized Clinical Trial for Evaluating the Safety and Feasibility of Fecal Microbiota Transplant (FMT) in Stage II-III Non-small Cell Lung Cancer (NSCLC) Patients, Using Immune Checkpoint Inhibitors (ICI) Responders as Donors.

This is a randomized, phase II, multi-centre clinical trial.
Sample size: 68 patients (Experimental Arm (Durvalumab + chemotherapy + FMT capsules): 34 patients, Control Arm (Durvalumab + chemotherapy): 34 patients)
Population: Patients with stage IIA, IIB, IIIA and IIIB (only T3N2) non-small cell lung cancer
In the Experimental arm, patients will receive Fecal Microbiota Transplant. Once done, the patient will start neoadjuvant treatment with Durvalumab + Chemotherapy .
In the Control arm, patients will receive neoadjuvant treatment with Durvalumab + Chemotherapy.
After neoadjuvant/induction treatment every patient will be evaluated to decide if the patient is a candidate for surgery or not. Patients that are R0 after surgery will receive Adjuvant treatment with Durvalumab.
The primary objective is to evaluate the pathological Complete Response (pCR) rate.
The total trial duration will be 6.5 years approximately.

开始日期2026-09-15

申办/合作机构

Fundacion GECP

NCT07332351

/ Not yet recruiting临床2期IIT

Intravesical Nadofaragene Firadenovec With Neoadjuvant Chemotherapy and Durvalumab in Patients With Muscle Invasive Bladder Cancer (TRIFECTA)

This phase II trial tests the effect of intravesical nadofaragene firadenovec in combination with gemcitabine, cisplatin and durvalumab before (neoadjuvant) radical cystectomy (RC) in treating patients with muscle invasive bladder cancer. The combination of gemcitabine, cisplatin and durvalumab are already considered standard of care in the treatment of muscle invasive bladder cancer. This trial attempts to determine whether the addition of nadofaragene firadenovec to the current standard regiment is safe and can improve oncological outcomes for those with muscle invasive bladder cancer.
Nadofaragene firadenovec, a type of intravesical gene therapy, is a weakened adenovirus that carries a copy of the gene for interferon alfa-2b. This medication gets absorbed by the bladder and stimulates the bladder to naturally create interferon alfa-2b, which is thought to kill bladder cancer. Nadofaragene firadenovec is given in a solution that is placed directly into the bladder (intravesical) using a thin tube called a catheter. It is a medication that is already FDA approved for the treatment of non-muscle invasive bladder cancer. Gemcitabine is a chemotherapy drug that blocks the cells from making deoxyribonucleic acid and may kill tumor cells. Cisplatin is in a class of medications known as platinum-containing compounds. It works by killing, stopping or slowing the growth of tumor cells. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the tumor, and may interfere with the ability of tumor cells to grow and spread.

开始日期2026-09-01

申办/合作机构

University of Washington

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100 项与度伐利尤单抗相关的临床结果

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100 项与度伐利尤单抗相关的转化医学

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100 项与度伐利尤单抗相关的专利（医药）

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2,279

项与度伐利尤单抗相关的文献（医药）

2026-07-01·LUNG CANCER

Prognostic value of serum CYFRA21-1 in locally advanced non-small cell lung cancer undergoing durvalumab consolidation therapy after chemoradiotherapy

Article

作者: Uchibori, Ken ; Ariyasu, Ryo ; Tsugitomi, Ryosuke ; Nemoto, Teruhisa ; Nibuya, Kyujiro ; Amino, Yoshiaki ; Fujishima, Shunsuke ; Yanagitani, Noriko ; Iso, Hirokazu ; Sugai, Mayu ; Nishio, Makoto ; Ito, Masahiro

INTRODUCTION:

Chemoradiotherapy (CRT) followed by durvalumab consolidation therapy is the standard treatment for locally advanced non-small cell lung cancer (LA-NSCLC), but robust prognostic biomarkers are lacking. This study evaluated the prognostic value of CYFRA 21-1, a serum marker associated with squamous cell carcinoma, in this setting.

METHODS:

Patients with LA-NSCLC were retrospectively reviewed according to treatment (CRT plus durvalumab group vs. CRT-only group). Patients with high and normal CYFRA 21-1 levels were compared within each group, using a threshold of 3.5 ng/mL. Overall survival (OS) and real-world progression-free survival (rw-PFS) were estimated using the Kaplan-Meier method and compared using the log-rank test. Multivariate analyses were conducted using Cox proportional hazards models.

RESULTS:

There were 134 patients in the CRT plus durvalumab group and 100 patients in the CRT-only group. In the CRT plus durvalumab group, patients with high CYFRA 21-1 levels had shorter median OS versus those with normal levels (38.8 vs. 73.4 months; HR, 2.49 [95% CI, 1.31-4.72]; p < 0.05), whereas no significant difference was observed within the CRT-only group (26.2 vs. 46.5 months; HR, 1.37 [95% CI, 0.82-2.27]; p = 0.21). A similar trend in OS was observed among those with non-squamous histology. On multivariate analysis, CYFRA 21-1 emerged as an independent prognostic factor in the CRT plus durvalumab group (HR = 2.21 (95% CI: 1.10-4.44), p < 0.05). Elevated CYFRA 21-1 levels were associated with shorter rw-PFS only in the CRT plus durvalumab group.

CONCLUSION:

CYFRA 21-1 may serve as a prognostic biomarker among patients with LA-NSCLC treated with CRT followed by durvalumab consolidation therapy.

2026-06-01·EUROPEAN JOURNAL OF CANCER

Gastric cancer: French intergroup clinical practice guidelines for diagnosis, staging, treatment and follow-up (TNCD, SNFGE, FFCD, UNICANCER, GERCOR, SFCD, SFED, AFEF, SFRO, SFP, SFR, ACHBPT, RENAPE, SNFCP)

Review

作者: Abdelghani, Meher Ben ; Ducreux, Michel ; Dubreuil, Olivier ; Jary, Marine ; Renaud, Florence ; Palle, Juliette ; Zaanan, Aziz ; Gagniere, Johan ; Mariani, Antoine ; Buecher, Bruno ; Barret, Maximilien ; Chapelle, Nicolas ; Durand-Labrunie, Jerome ; Palmieri, Lola-Jade ; Bouché, Olivier ; Fares, Nadim

INTRODUCTION:

The updated edition of the French intergroup guidelines for the management of patients with gastric and gastroesophageal junction adenocarcinoma is a collaborative work of several national medical societies, and available on the website of the French Society of Gastroenterology (SNFGE) (www.tncd.org).

METHODS:

The recommendations are graded into three categories (A, B, and C), based on the level of scientific evidence published until January 2026.

RESULTS:

Initial staging and risk assessment should include physical evaluation, endoscopy and computed tomography-scan of the thorax, abdomen, and pelvis. For resectable disease, endoscopic ultrasonography can be used for T and N staging, while laparoscopic exploration may be performed to exclude occult peritoneal metastases, especially for cT3/cT4 and poorly cohesive tumors. Endoscopic or surgical resection alone is appropriate for very early cT1N0 tumors. For locally advanced disease ≥cT2 and/or cN + , the perioperative FLOT chemotherapy is recommended as the standard of care. Recently, the addition of durvalumab to perioperative FLOT followed by durvalumab for 10 months as maintenance therapy was associated with a significant improvement of survival. For metastatic disease, the first-line chemotherapy is based on platinum-fluoropyrimidine combination. The addition of targeted therapy and/or immunotherapy to doublet chemotherapy depends on the tumor biomarker profile, including HER2 (trastuzumab), claudin18.2 (zolbetuximab), PD-L1 and dMMR/MSI phenotype (anti-PD1 monoclonal antibodies). The addition of docetaxel, based on the triplet TFOX regimen may be considered for selected patients with biomarker-negative tumors. Resection of primary tumor and metastases cannot be recommended but may be considered on an individual basis in highly selected patients with oligometastatic disease who respond to systemic treatment. Various drugs are indicated beyond first-line of treatment, including trastuzumab-deruxtecan for HER2-positive tumors.

CONCLUSION:

These national guidelines on gastric cancer are intended to facilitate decision-making in daily clinical practice. These recommendations are subject to ongoing review. Each individual case should be discussed within a multidisciplinary team.

2026-06-01·EUROPEAN JOURNAL OF CANCER

Censoring patterns and inconsistent results in checkpoint inhibitor and adjuvant BCG trials for high-risk bladder cancer

Article

作者: Olivier, Timothée ; Tsantoulis, Petros ; Develtere, Dries

Intravesical Bacillus Calmette-Guérin (BCG) is the standard-of-care treatment for high-risk non-muscle invasive bladder cancer (HR-NMIBC). However, patients with BCG-unresponsive disease are unlikely to benefit from further BCG. To overcome BCG unresponsiveness, the addition of immune checkpoint inhibition (ICI) to BCG has been investigated in three recently randomized controlled trials: CREST, POTOMAC, and ALBAN, studying sasanlimab, durvalumab, and atezolizumab, respectively. While CREST and POTOMAC demonstrated improvements in event/disease-free survival (EFS/DFS), ALBAN was negative. Several potential explanations have been proposed for these discrepant findings. We propose an additional explanation: censoring. In the experimental arm, toxicity-related discontinuation may preferentially remove frailer patients, artificially enriching the remaining population for healthier individuals potentially biasing EFS or DFS. We explored censoring patterns across trials and conducted sensitivity analyses based on reconstructed Kaplan-Meier curves, and modifying only a few patients in POTOMAC and CREST eroded the EFS/DFS benefit as reported. The addition of immunotherapy to BCG significantly increases toxicity, and supports that some level of toxicity-related informative censoring might have differentially affected the three trials. Informative censoring may represent an important, underrecognized explanation for the inconsistent efficacy results reported across ICI plus BCG trials. More broadly, given the expanding use of immunotherapy in earlier disease settings and the reliance on time-to-event endpoints in open-label trials with differential toxicity, systematic attention to censoring mechanisms is essential for accurate interpretation.

2,905

项与度伐利尤单抗相关的新闻（医药）

19 小时之前

·ioncology

ASCO 2026丨美国纽约纪念斯隆-凯特琳癌症中心Ghassan K. Abou-Alfa教授：EMERALD-3 Ⅲ期研究确立eeHCC治疗新标准

编者按：在2026年美国临床肿瘤学会（ASCO）年会上，备受瞩目的EMERALD-3 Ⅲ期研究（摘要号：LBA4000）以口头报告形式重磅发布。《肿瘤瞭望消化时讯》特邀该研究讲者美国纽约纪念斯隆-凯特琳癌症中心（MSKCC）Ghassan K. Abou-Alfa教授进行点评。 Ghassan K. Abou-Alfa教授指出，EMERALD-3是首个证实STRIDE方案（曲麦利尤单抗+度伐利尤单抗）联合经动脉化疗栓塞术（TACE）能够为不可切除且适合接受栓塞治疗的肝细胞癌（eeHCC）患者带来显著生存获益的Ⅲ期临床试验；尤为重要的是，该获益独立于仑伐替尼的使用，从而确立了其作为此类患者潜在新标准治疗选择的地位。以下是具体点评内容和研究介绍。《肿瘤瞭望消化时讯》 ✓ 请您介绍一下对于不可切除的肝细胞癌，曲麦利尤单抗+度伐利尤单抗双免联合±仑伐替尼联合TACE的核心疗效优势是什么？ Ghassan K. Abou-Alfa教授二十余年来，TACE一直是eeHCC的全球标准疗法，可使患者中位无进展生存期（PFS）达到8~10个月。曲麦利尤单抗（tremelimumab）单次给药联合度伐利尤单抗（durvalumab）常规每月维持治疗，是晚期HCC的一线标准疗法，并且在6年的随访中，与索拉非尼相比，显示出持续的总生存期（OS）获益。鉴于TACE可通过释放肿瘤抗原诱导免疫检查点上调，将TACE与免疫治疗（无论是否联用抗血管生成药物）相结合，有望进一步增强抗肿瘤活性。 Dr Ghassan K. Abou-Alfa: TACE has been a global standard of care for unresectable, embolization-eligible HCC for over 20 years. TACE offers a median PFS of 8~10 months. Single dose of tremelimumab and regular monthly interval durvalumab is a frontline standard of care in advanced HCC and has shown sustained OS benefit through 6 years of follow-up vs sorafenib. TACE releases tumor antigens, which upregulate immune checkpoints. Thus, combining TACE with immunotherapy with or without anti-angiogenic therapies may enhance antitumor activity. 《肿瘤瞭望消化时讯》 ✓ 在双免疫+TACE的基础上加用仑伐替尼，安全性特征如何，临床中应如何平衡疗效提升与额外毒性风险？ Ghassan K. Abou-Alfa教授在所有不良事件中，导致仑伐替尼的用药中断的AE发生率约79%，约50%的病例需要下调剂量。此外，导致仑伐替尼永久停药的AE发生率约30%。 Dr Ghassan K. Abou-Alfa: Of all adverse events close to 79% led to the interruption of lenvatinib. Dose reduction was required in close to 50% of the cases. Of all adverse events, about 30% led to discontinuation of lenvatinib. 《肿瘤瞭望消化时讯》 ✓ 对于不同基线状态的不可切除HCC患者，两种联合方案的疗效是否存在亚组差异？ Ghassan K. Abou-Alfa教授所有三个研究组的人口统计学特征均保持平衡，但仍观察到一些细微差异。例如，尽管样本量较小，但值得注意的是，在日本患者中，TACE联合STRIDE方案和仑伐替尼的PFS有所改善。然而，目前仍缺乏明确的机制阐释来证明这种差异的有效性。 Dr Ghassan K. Abou-Alfa: All demographics were balanced in all three stud arms. Subtle differences were noted though. A good example is despite the small sample size, the improved PFS in arm of TACE plus STRIDE and lenvatinib among patients from Japan is worth noting. This is despite we continue to lack a clear explanation if this difference ends up being valid. 《肿瘤瞭望消化时讯》 ✓ 基于EMERALD-3研究结果，您认为这种以双免为基础的联合TACE方案，将如何重塑不可切除HCC治疗格局？ Ghassan K. Abou-Alfa教授 EMERALD-3研究是首项证实基于STRIDE方案联合TACE可改善eeHCC临床结局的Ⅲ期临床试验，且该获益不受仑伐替尼使用与否的影响，从而支持了其作为eeHCC潜在新治疗选择的地位。 Dr Ghassan K. Abou-Alfa: The Emerald-3 study represents the first Phase 3 study to demonstrate that a STRIDE-based regimen improves clinical outcomes when combined with TACE, independent of lenvatinib use, supporting its role as a potential new treatment option in unresectable embolization eligible HCC. EMERALD-3研究介绍标题：Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). EMERALD-3研究的疗效和安全性结局：一项Ⅲ期随机研究，评估曲麦利尤单抗+度伐利尤单抗±仑伐替尼联合TACE治疗eeHCC患者的疗效研究背景 TACE是eeHCC的全球标准治疗方案（SoC），其可通过诱导肿瘤免疫应答发挥作用。STRIDE（曲麦利尤单抗[T]单次给药+度伐利尤单抗[D]维持治疗）方案在6年随访中显示出OS获益，并成为不可切除晚期HCC的标准疗法（图1）。在此，研究者报告了EMERALD-3研究（NCT05301842）的预设分析结果，该研究旨在评估STRIDE方案（无论是否联用仑伐替尼[L]）联合TACE的疗效与安全性。图1. EMERALD-3研究背景研究方法符合条件的（≥18岁）确诊为eeHCC的患者按1:1:1的比例随机分组，分别接受STRIDE（第1天给予T 300 mg + D 1500 mg，之后每4周给予D 1500 mg）+L（每日8或12 mg）+TACE治疗；STRIDE+TACE治疗；或单纯TACE治疗，直至每组达到175例患者。随机分组仍以1:1的比例进行，直至STRIDE+L+TACE组和单纯TACE组每组达到275例患者。D和L的治疗持续≤36个月，直至疾病进展、出现不可耐受的毒性反应或患者撤回知情同意。根据Up-To-Seven标准，按地区、既往姑息性栓塞治疗史和基线肿瘤负荷对患者进行分层。主要终点为STRIDE+L+TACE组对比单纯TACE组的PFS，采用分层Cox比例风险模型和分层对数秩检验进行分析。关键次要终点包括：STRIDE+L+TACE组对比单纯TACE组的总生存期（OS），以及STRIDE+TACE组对比单纯TACE组的PFS与OS（图2）。图2. EMERALD-3研究设计研究结果截至2026年2月23日，共有293例患者随机分配至STRIDE+L+TACE组，175例分配至STRIDE+TACE组，292例分配至TACE组。各组基线特征基本均衡。与TACE组相比，STRIDE+L+TACE组的PFS显著改善（HR=0.70；95%CI，0.57~0.86；P=0.0007），OS也呈现改善趋势（HR=0.84；95%CI，0.65~1.09；P=0.1814）（图3,4）。与TACE组相比，STRIDE+TACE组的PFS（HR=0.71；95%CI，0.56~0.91）和OS（HR=0.70；95%CI，0.51~0.95）也得到改善（图5,6）。与TACE相比，STRIDE±L+TACE组的24个月OS率更高。STRIDE+L+TACE组、STRIDE+TACE组和TACE组3/4级以上治疗相关不良事件发生率分别为62.7%、48.6%和18.6%（图7）。图3. STRIDE+L+TACE vs. TACE的PFS 图4. STRIDE+L+TACE vs. TACE的OS 图5. STRIDE+TACE vs. TACE的PFS 图6. STRIDE+TACE vs. TACE的OS 图7. AE发生情况研究结论 EMERALD-3研究证实，STRIDE+L+TACE较单纯TACE显著改善eeHCC患者的PFS。在中期分析时（数据成熟度≤45%），观察到STRIDE±L+TACE较单纯TACE呈现出积极的OS获益趋势。此外，STRIDE+TACE方案亦较单纯TACE显著改善了PFS。所有不良事件均与各疗法已知的安全性特征一致。综上，EMERALD-3研究结果支持STRIDE±L+TACE作为eeHCC的潜在新治疗选择。《肿瘤瞭望消化时讯》在2026 ASCO现场报道参考文献[1] Ghassan K Abou-Alfa，et al. Efficacy and safety results from EMERALD-3: A phase 3, randomized study of tremelimumab plus durvalumab with or without lenvatinib combined with transarterial chemoembolization (TACE) in participants (pts) with unresectable embolization-eligible hepatocellular carcinoma (eeHCC). 2026 ASCO LBA 4000. （来源：肿瘤瞭望消化时讯）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。

21 小时之前

·Biotech前瞻

斯鲁利单抗：国内首个胃癌围术期PD-(L)1单抗上市，带来化疗之外的新选择

点击蓝字关注我们本期看点胃癌围术期治疗曾是一片屡遭挫折的“险滩”。尽管免疫疗法在晚期胃癌中已证实价值，但包括O药、K药在内的多个PD-1/L1抑制剂在冲击围术期治疗的III期研究中均未能达到主要终点，让领域一度蒙上阴影。然而，这一僵局在近期被彻底打破：先是阿斯利康的度伐利尤单抗凭借MATTERHORN研究的阳性结果获FDA批准，并获NCCN指南重磅升级为1类优选方案；几乎同时，国产PD-1斯鲁利单抗宣布其III期ASTRUM-006研究成功，并被CDE纳入突破性治疗品种。 6 月 9 日，NMPA 官网显示，复宏汉霖 PD-1 单抗「斯鲁利单抗」一项新适应症获批上市，联合含铂化疗新辅助治疗，在手术后辅助治疗，用于 PD-L1 阳性、可手术切除的胃癌患者。截图来源：NMPA 官网来源：CDE 官网标志着胃癌围术期治疗正式从化疗时代迈入免疫治疗新时代，为追求根治的早期患者带来了前所未有的希望。本期内容 01 围术期迎来“单免疫+化疗”新时代 02 单靶点路线的经验与教训 03 04 双抗II期探索的信号总结与展望【01 围术期迎来“单免疫+化疗”新时代】胃癌围术期免疫治疗走过了一条曲折的道路。早期KEYNOTE-585、ATTRACTION-05等研究虽在新辅助阶段提高了pCR率，却未能在整体人群中实现EFS/OS的统计学显著改善，让业界对"围术期+PD-1/L1"一度信心受挫。转折发生在2025年：MATTERHORN III期试验证实度伐利尤单抗联合FLOT围术期治疗可显著降低复发/进展或死亡风险29%，并带来3年OS改善，推动FDA批准"度伐利尤单抗+FLOT"成为首个胃癌/GEJ围术期免疫方案。 MATTERHORN 研究设计几乎同一时间，ASTRUM-006证实斯鲁利单抗+SOX在围术期显著改善EFS，并首创"术后以免疫单药替代辅助化疗"的设计。 ASTRUM-006研究设计首次成功验证了以免疫单药替代术后辅助化疗的可行性：试验组采用“斯鲁利单抗+化疗”新辅助治疗后，直接使用斯鲁利单抗单药进行术后辅助；而对照组则沿用传统的术后化疗。结果显示，该方案不仅将pCR率提升至对照组的3倍以上，更显著延长了EFS。这种“去化疗”模式若能成功上市，将极大改变治疗格局，为患者提供毒性更低、依从性更高的新选择。 02 单靶点路线的经验与教训从已公布的III期证据看，单靶点PD-1/L1在围术期胃癌的表现可谓"有突破、也有边界"。MATTERHORN采用FLOT作为化疗方案，度伐利尤单抗+FLOT将pCR从7%提高到19%，EFS和OS也实现统计学显著改善，且获益基本不依赖PD-L1状态。 ASTRUM-006则在SOX基础上通过"新辅助免疫+化疗+术后免疫单药"实现EFS阳性，pCR约是对照组的3倍。与之形成对比的是KEYNOTE-585和ATTRACTION-05：前者pCR从2.0%提升到13.4%，EFS/OS的HR在0.8左右徘徊，却未达预设统计学门槛；后者在整体人群的RFS上同样未显著改善。这些结果共同提示：并非"任何化疗+任何PD-1"都能在围术期跑赢化疗，FLOT、SOX等方案在免疫原性上的差异很可能影响结局；高MSI、PD-L1 CPS≥10等"免疫热"亚组获益更为清晰，提示人群异质性极强；pCR/MPR的提升并不必然转化为EFS/OS的显著延长，pCR更像是"有用但不完美"的替代终点。【03 双抗II期探索的信号】在单靶点路线逐渐清晰的同时，PD-1/CTLA-4双抗也开始在围术期进行探索。 2025年ESMO Asia报告的COMPASSION-25是卡度尼利单抗联合SOX用于可切除G/GEJ腺癌的新辅助II期研究：在28例可评估患者中，整体pCR率28.6%，D1、Q3W给药方案下pCR高达50%；MPR率71.4%，全部患者实现R0切除。安全性方面，联合方案的毒性谱整体与SOX+免疫相符，尚未出现新的安全信号。结合既往晚期一线COMPASSION-15中，卡度尼利+化疗已在整体人群中带来OS获益，并在中国获批晚期一线适应证，双抗在胃癌领域的"抗肿瘤实力"已有坚实基础。围术期层面，正在推进的COMPASSION-33 III期研究采用"卡度尼利+SOX围术期vs安慰剂+SOX"的随机设计，主要终点包括EFS、R0切除率等，希望验证II期中的病理与降期优势能否转化为长期生存获益。但需要强调的是：目前双抗在围术期的证据仍停留在小样本II期病理终点，尚无EFS/OS阳性的随机对照数据；PD-1/CTLA-4联合可能带来更高的免疫相关毒性风险，尤其是在手术前后对创口愈合、并发症控制的影响需要更系统评估。 04 总结与展望胃癌围术期正从"化疗一条路"走向"多种免疫策略并存"的新阶段。对临床来说，下一步需要思考的问题已经不是"要不要加免疫"，而是"在什么人、用哪种方案、用到什么强度、用多长时间"：人群层面，弥漫型、Lauren分型、MSI、PD-L1 CPS等因素已体现出显著异质性；方案层面，FLOT+度伐利尤已完成监管闭环，适合有条件接受强化化疗的中心；SOX+PD-1并"去化疗"的设计更适合希望减轻毒性负担的人群；双抗+SOX目前仍应主要在临床试验中应用。当同一患者可能在晚期一线及围术期都面临免疫治疗选择时，如何在"提高治愈率"和"保留后线空间"之间平衡，将成为真实世界决策的新议题。对研发企业而言，围术期不再是简单地把晚期一线经验"平移"，而需要在终点选择、生物标志物分层、化疗骨架搭配等方面做更精细设计。单靶点的坎坷经验、双抗II期的积极信号，共同构成了胃癌围术期免疫"从晚期走向根治意图"的关键一步——但在真正把治愈率抬上新台阶之前，或许更需要的是：在兴奋之余，多留几个问号，多做几项扎实的III期试验。 ★

2026-06-08

·小药说药

免疫检查点抑制剂相关胃肠道毒性

-01- 引言 2011年，美国食品药品监督管理局（FDA）批准了伊匹木单抗，一种靶向细胞毒性T淋巴细胞相关蛋白4（CTLA-4）的单克隆抗体，用于治疗晚期黑色素瘤。随后，抗程序性细胞死亡蛋白1（PD-1）抗体（如纳武利尤单抗和帕博利珠单抗）及其配体PD-L1的抗体（如阿替利珠单抗和度伐利尤单抗）也相继获批，将免疫检查点抑制剂的临床应用扩展到非小细胞肺癌、肾细胞癌、头颈部鳞状细胞癌和肝细胞癌等多种恶性肿瘤。 ICI开创了肿瘤免疫的新格局，但它们也可能改变免疫稳态，导致免疫系统异常攻击健康组织，从而引发免疫相关不良事件（irAEs）。其中胃肠道irAEs——包括肝炎和结肠炎——最为常见。这些毒性具有免疫介导的特性，与传统化疗的不良反应存在本质区别。 -02- 一、ICI的胃肠道irAE流行病学胃肠道毒性的发生率和临床表现因ICI类型而异。CTLA-4抑制剂的的胃肠道相关irAEs频率更高，更炎症，尤其是结肠炎，而PD-1或PD-L1抑制剂的胃肠道毒性则较轻。伊匹木单抗单药治疗中，腹泻发生率为23–33%，结肠炎为8–12%，其中3–4级腹泻和结肠炎分别约为3–6%和7–9%。肝炎发生率为1–7%，3–4级肝炎约为0–2%。 PD-1/PD-L1抗体的腹泻发生率约为11–19%，结肠炎约为1–4%，其中3–4级腹泻和结肠炎约为1–3%和<1%。肝炎发生率约为1–6%，3–4级肝炎约为1–3%。值得注意的是，抗PD-1抗体的结肠炎发生率显著高于抗PD-L1抗体。联合治疗方面，，胃肠道 irAEs发生率显著增高，腹泻约为44–45%，结肠炎约为12–26%，3–4级腹泻和结肠炎约为9–11%和8–17%。肝炎约为13–30%，3–4级肝炎约为6–19%。此外，不同癌症类型与irAE风险也存在关联，例如黑色素瘤患者易发生irAE结肠炎，而胸腺癌患者更易发生肝脏irAE。 -03- 二、肝炎irAE 肝脏irAE通常发生在ICI治疗开始后6至14周，但时间变异很大。肝脏irAE常无症状，有症状的患者可能出现乏力、厌食、黄疸或右上腹不适。生化上，肝脏irAE多表现为肝细胞损伤模式，ALT和AST升高，而ALP和胆红素相对正常。组织病理学检查常见以CD8+ T细胞浸润为主的肝小叶炎症、局灶性肝细胞坏死和肝窦内皮细胞损伤。驱动肝脏irAE的机制是多方面的，目前并不完全清楚。现有证据表明，与药物性肝损伤（DILI）或自身免疫性肝炎（AIH）不同，肝脏irAE中的肝损伤主要源于ICI治疗诱导的外周免疫耐受丧失。ICIs通过解除抑制性信号来放大抗肿瘤免疫，但也可能破坏免疫稳态，促进自身反应性CD8+细胞毒性T细胞浸润至肝小叶，导致直接肝细胞损伤。另一个可能得机制涉及调节性T细胞介导的耐受性破坏。由于CTLA-4在Tregs上大量表达，阻断后可能损害Treg的免疫抑制能力，导致肝脏组织内免疫激活失控。此外，辅助T细胞（Th1和Th17亚群）也参与发病机制，通过分泌细胞毒性和促炎细胞因子促进炎症。肝脏irAE的严重程度根据CTCAE分级，管理策略根据分级而定： Grade 1：可继续治疗，密切监测肝酶。 Grade 2：需要暂停ICI，必要时需给予糖皮质激素（口服泼尼松0.5–1 mg/kg/天）。若肝酶改善，逐步减量。 Grade 3/4：需要停用ICI，并给予高剂量糖皮质激素（如甲泼尼龙1–2 mg/kg/天）。若72小时内仍然无改善，可加用其他免疫抑制剂如霉酚酸酯。这些建议遵循ASCO和ESMO临床实践指南。关于ICI再挑战，研究显示既往严重肝炎后再次接受ICI治疗的患者中，有34.8%的患者会复发肝炎。 -04- 三、结肠炎irAE 结肠炎irAE通常在治疗开始后5至10周内发生。临床上，ICI诱导的结肠炎典型表现为水样腹泻，伴有腹部绞痛、紧迫感和偶尔的黏液或血便。严重的可能出现脱水、发热、体重减轻和明显结肠炎症体征。实验室检查可能包括CRP等炎症标志物增高。组织学上，活检标本常见淋巴细胞或混合性炎症细胞浸润、隐窝脓肿和上皮损伤。 ICI诱导的结肠炎的病理生理复杂，主要还是归咎于检查点阻断后的免疫失调。CTLA-4阻断诱导的结肠炎通常比PD-1/PD-L1抑制剂更频繁，更严重。组织学上，ICI治疗引起的结肠炎常类似于IBD（尤其是溃疡性结肠炎），表现为由CD4+和CD8+ T细胞浸润的固有层和上皮、隐窝脓肿形成以及凋亡上皮细胞增多。 irAE结肠炎的诊断需要综合评估，临床管理根据严重程度而定： Grade 1：可继续免疫治疗，需要进行严密监测和对症治疗。 Grade 2及以上：需要暂停或停用ICI，进行适当诊断评估以排除感染或其他原因。对于持续或严重症状：推荐使用糖皮质激素（口服泼尼松或静脉甲泼尼龙1–2 mg/kg/天）。 Grade 4患者：需永久停药，严重者可考虑粪菌移植、托法替尼等。恢复后，要谨慎考虑重启PD-1/PD-L1抑制剂的治疗。 -05- 结语 ICIs治疗癌症虽然效果卓越，但常伴有胃肠道irAEs，尤其是肝炎和结肠炎。这两种irAE都需要及时诊断、排除其他病因，并根据严重程度进行个体化管理。参考文献： Immune checkpoint inhibitor-associated hepatitis and colitis: current understanding and clinical approaches. Immunol Med. 2026 Jun 2:1-13.

100 项与度伐利尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D10808	度伐利尤单抗	L01XC28	DB11714

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
非肌层浸润性膀胱肿瘤	美国	AstraZeneca UK Ltd.	2026-05-28
胃癌	欧盟	AstraZeneca AB	2026-03-16
胃癌	冰岛	AstraZeneca AB	2026-03-16
胃癌	列支敦士登	AstraZeneca AB	2026-03-16
胃癌	挪威	AstraZeneca AB	2026-03-16
早期胃癌	美国	AstraZeneca PLC	2025-11-25
胃食管交界处腺癌	美国	AstraZeneca UK Ltd.	2025-11-25
胃食管交界处癌	美国	AstraZeneca PLC	2025-11-25
局部晚期胃癌	美国	AstraZeneca PLC	2025-11-25
不可切除的非小细胞肺癌	中国	AstraZeneca UK Ltd.	2025-11-18
肌层浸润性膀胱癌	美国	AstraZeneca UK Ltd.	2025-03-28
子宫癌	日本	阿斯利康制药有限公司	2024-11-22
晚期子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
晚期子宫内膜癌	挪威	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	欧盟	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	冰岛	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	列支敦士登	AstraZeneca AB	2024-08-15
复发性子宫内膜癌	挪威	AstraZeneca AB	2024-08-15

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
ALK阳性非小细胞肺癌	申请上市	中国	AstraZeneca AB	2025-02-21
EGFR突变的非小细胞肺癌	申请上市	中国	AstraZeneca UK Ltd.	2025-02-21
卵巢上皮癌	申请上市	中国	AstraZeneca UK Ltd.	2024-08-16
错配修复功能正常的微卫星稳定型结肠癌	临床3期	西班牙	AstraZeneca PLC	2024-12-30
PD-L1阳性三阴性乳腺癌	临床3期	美国	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	中国	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	日本	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	阿根廷	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	澳大利亚	AstraZeneca PLC	2023-11-23
PD-L1阳性三阴性乳腺癌	临床3期	巴西	AstraZeneca PLC	2023-11-23

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适应症

分期

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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


NCT03691714 (P397, CTgov)	临床2期	复发性头颈癌 \| 转移性头颈部鳞状细胞癌 \| 转移性肿瘤	35	Cetuximab+Durvalumab	鬱壓鬱鹹艱餘鬱網糧醖 = 網艱壓廠構衊夢簾淵膚鑰範獵廠齋鏇淵餘蓋鹽 (襯築獵廠鹹遞餘選窪簾, 鹽選獵鬱觸觸醖齋齋憲 ~ 齋餘獵構遞衊鹽齋願餘) 更多	-	2026-06-01
NCT06464068 (DURVASCC, ASCO2026)	临床2期	广泛期小细胞肺癌一线	20	Durvalumab 1500 mg + Carboplatin AUC5-6 or Cisplatin 75-80 mg/m2 + Etoposide 80-100 mg/m2	鹹鏇窪醖蓋淵鏇選淵築(鏇夢製顧範窪繭憲鏇願) = 齋醖衊艱願築艱製膚餘鹽糧憲鬱製製獵願窪築 (蓋齋鹽鬱衊網膚淵壓憲 ) 更多	积极	2026-05-29
RAD-IO (ASCO2026)	临床2期	肌层浸润性膀胱癌辅助	55	Durvalumab with chemoradiotherapy with 5-fluorouracil and mitomycin C	醖餘獵壓選選遞蓋鏇鹹(獵淵衊蓋願膚築餘憲艱) = 製淵廠廠願範壓鬱窪廠廠膚餘餘鏇鑰構廠糧夢 (繭鬱構醖繭選遞鑰壓餘, 66 ~ 88) 更多	积极	2026-05-29
NCT04517227 (ASCO2026)	临床2期	不可切除的肝细胞癌	30	Transarterial chemoembolization (TACE) + Ablation + Durvalumab	築簾積壓構遞積繭膚遞(範選膚鏇衊簾鏇窪製鏇) = 14 (46.7%) reported grade 1-2 AESIs possibly related to durvalumab: 7 (23.3%) elevated liver enzymes, 6 (20.0%) elevated lipase, 4 (13.3%) abnormal thyroid function, 2 (6.7%) elevated amylase, 2 (6.7%) rashes, and 1 (3.3%) interstitial pneumonia. However, only the 1 patient with interstitial pneumonia required oral corticosteroids for management. 鹽範遞窪簾願顧積醖壓 (製壓壓窪簾鹹餘醖蓋夢 ) 更多	积极	2026-05-29
NCT04517227 (ASCO2026)	临床2期	不可切除的肝细胞癌	30	Transarterial chemoembolization (TACE) + Ablation + Durvalumab (PP set)		积极	2026-05-29
ASCO2026	N/A	非小细胞肺癌	289	Non-taxane based chemotherapy	鹽鹹齋築獵簾窪鬱範願(製獵觸鹽築顧鑰鬱艱鹹) = 廠鑰壓憲築憲窪憲醖艱築膚築簾醖衊築積網憲 (襯鹽選廠衊遞廠鬱積窪 ) 更多	积极	2026-05-29
ASCO2026	N/A	非小细胞肺癌	289	Taxane based chemotherapy	鹽鹹齋築獵簾窪鬱範願(製獵觸鹽築顧鑰鬱艱鹹) = 齋觸顧選壓顧構顧觸窪築膚築簾醖衊築積網憲 (襯鹽選廠衊遞廠鬱積窪 )	积极	2026-05-29
PACIFIC (ASCO2026)	临床3期	非小细胞肺癌 PD-L1	724	Durvalumab	淵窪鬱廠廠獵構蓋選繭(醖鑰衊鏇簾廠選簾鬱鬱): RR = 1.17, P-Value = 0.005 更多	积极	2026-05-29
PACIFIC (ASCO2026)	临床3期	非小细胞肺癌 PD-L1	724	Placebo	淵窪鬱廠廠獵構蓋選繭(醖鑰衊鏇簾廠選簾鬱鬱): RR = 1.17, P-Value = 0.005 更多	积极	2026-05-29
ASCO2026	N/A	局部晚期非小细胞肺癌 KRAS \| TP53 \| STK11 ... 更多	290	Platinum-based ChRT (KRAS-mutant)	網鹹鏇膚範繭襯觸夢憲(築蓋願齋廠觸鹹齋顧範) = 糧製齋製遞遞廠願繭糧鹹蓋製鏇築製鹽願鹽膚 (艱齋構構蓋鏇簾醖憲願, 30.0 ~ 59.4) 更多	积极	2026-05-29
NCT03991832 (ASCO2026)	临床2期	胆管癌 IDH1/2 mutations	10	Durvalumab 1500 mgOlaparib 300 mg + Durvalumab 1500 mgOlaparib 300 mg mg (IDH-mutant cholangiocarcinoma)	遞構築鏇憲網鹹壓蓋築(鏇築構鏇鑰鹹製範鏇廠) = 鹽鏇衊廠鬱積艱顧遞鏇鑰窪憲鏇鬱糧蓋願獵淵 (齋餘繭鬱蓋築夢淵簾衊 ) 更多	不佳	2026-05-29
NCT03851614 (ASCO2026)	临床2期	平滑肌肉瘤 active chromatin-associated cell-free DNA	52	durvalumab + olaparib or cediranib	範餘壓夢醖夢壓壓憲鏇(製窪簾鏇淵艱遞醖窪夢) = 齋範鑰選淵壓齋積窪選製鏇憲艱蓋膚繭鏇憲鹹 (鹽鑰築構衊鹹醖繭夢壓 ) 更多	积极	2026-05-29
NCT03851614 (ASCO2026)	临床2期	平滑肌肉瘤 active chromatin-associated cell-free DNA	52	durvalumab + olaparib or cediranib (Disease Progression)	範餘壓夢醖夢壓壓憲鏇(製窪簾鏇淵艱遞醖窪夢) = 網糧廠鏇築襯襯構簾顧製鏇憲艱蓋膚繭鏇憲鹹 (鹽鑰築構衊鹹醖繭夢壓 )	积极	2026-05-29
NCT04568200 (ASCO2026)	临床2期	局部晚期食管鳞状细胞癌新辅助	34	Durvalumab + Concurrent chemoradiotherapy	願廠齋鏇膚膚鹹顧餘網(齋窪襯積窪廠衊鹹簾艱) = 衊壓餘憲襯衊衊遞鏇壓積獵築鑰積醖積顧積繭 (選繭製簾窪鏇積製壓簾 ) 更多	积极	2026-05-29