STRIVE: A Single-arm Phase 2 Study on Treatment of Lung Squamous Cell Carcinoma by Tiragolumab Plus Ivonescimab for Patients Who Progressed on Platinum Doublets and Anti-PD-1/PD-L1

To learn if the drug combination of tiragolumab and ivonescimab can help to control LSCC that got worse after standard treatment with platinum doublets and anti-PD-1/PD-L1 therapy.

开始日期2025-12-03

申办/合作机构

The University of Texas MD Anderson Cancer Center

NCT06603818

/ Recruiting临床2期IIT

A Phase II Study of Immunotherapies (Tiragolumab and Atezolizumab) in Combination With Stereotactic Body Radiation Radiotherapy in Microsatellite Stable (MSS) Metastatic Colorectal Cancer (mCRC)

Background:
Metastatic colorectal cancer (mCRC) is cancer that has spread beyond the colon and rectum. Most people with mCRC die within 5 years. New immune-based treatments are making progress with some types of colon cancer. But these treatments do little for people with a type of cancer that is microsatellite stable (MSS). MSS is a specific cancer biomarker. Better treatments are needed.
Objective:
To test 2 drugs (tiragolumab and atezolizumab) combined with radiation therapy in people with MSS mCRC.
Eligibility:
People aged 18 years and older with MSS mCRC.
Design:
Participants will be screened. They will have a physical exam with blood tests. They will have imaging scans and a test of their heart function. They will provide a tissue sample from their tumor; if one is not already available, a new sample will be taken. Their ability to perform normal tasks will be assessed.
Tiragolumab and atezolizumab are both administered through a tube attached to a needle inserted into a vein. Participants will receive both drugs on day 1 of 3-week treatment cycles. Each study visit should last about 8 hours.
Participants will receive radiation therapy on days 1, 3, and 5 of cycle 1 only.
Blood samples and rectal swabs will be collected on day 1 of every cycle.
Imaging scans will be repeated every 9 weeks. Additional tumor samples may be taken during treatment.
Treatment will continue for up to 2 years.
Participants will have a follow-up visit 1 month after treatment ends. Follow-up visits will continue every 3 months for 1 more year.

开始日期2025-07-22

申办/合作机构

National Cancer Institute

NCT06713798

/ Not yet recruiting临床2期IIT

Targeting PD-L1 and TIGIT in Tumors With Tertiary Lymphoid Structures

This study encompasses multicenter open-label, phase II trials.
Patients will be dispatched into 2 cohorts:
* Cohort A: Patients naïve from systemic treatment will be randomized according to two treatment modalities: atezolizumab + tiragolumab (arm A1) versus atezolizumab monotherapy (arm A2).
43 patients are to be included in each arm.
* Cohort B: Patients with previous exposure to ICI will be treated with the combination of atezolizumab and tiragolumab.
29 patients are to be included in this cohort.

开始日期2025-07-01

申办/合作机构

Institut Gustave Roussy EURL

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100 项与替瑞利尤单抗相关的专利（医药）

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项与替瑞利尤单抗相关的文献（医药）

2025-05-01·CLINICAL PHARMACOLOGY & THERAPEUTICS

Model‐Informed Selection of the Recommended Phase 2 Dosage for Anti‐TIGIT Immunotherapy Leveraging co‐Expressed PD‐1 Inhibitor Target Engagement

Article

作者: Hu, Ping ; Venkatakrishnan, Karthik ; Gao, Wei ; Kareva, Irina ; Victor, Anja ; Kitzing, Thomas ; Richter, Emilia ; Pierre, Vadryn ; Zutshi, Anup

Refining dose projections requires a deep understanding of drug‐target relationships at the site of action, which is often challenging to achieve. Here we present a case study of how one can refine dose projections for a TIGIT‐targeted immunotherapy by leveraging information from the well‐studied PD‐1 pathway since the co‐expression of PD‐1 and TIGIT on immune cells provides a unique opportunity to extrapolate data from one target to inform the dosing strategy for the other. We develop a fit‐for‐purpose mathematical model that captures the experimentally observed relationship between the concentration of a mouse PD‐1 antagonist in the plasma and PD‐1 target engagement within the tumor microenvironment (TME). We then assess the applicability of this PD‐1 model to elucidate the relationship between drug concentration and target engagement for tiragolumab, an anti‐TIGIT antibody, across various doses. This analysis aims to refine our understanding of the dose–response relationship for targeting TIGIT, a critical step in optimizing therapeutic efficacy, without conducting additional experiments. The approach is then extended to project efficacious doses for M6223, another anti‐TIGIT antibody, using the established PD‐1 model, by leveraging the M6223 clinical PK and PD data, as well as virtual population analysis. This work provides a case study of a possible framework for refining dose projections via quantitative estimation of drug‐target relationship at the site of action by leveraging established drug‐target relationships. Through extrapolating information from a well‐characterized pathway, we offer a method to inform dose optimization strategies with limited data using model‐informed drug development.

2025-03-01·BMJ Open

NeoTRACK trial: Neoadjuvant TiRagolumab, Atezolizumab and Chemotherapy – dissection of IO- efficacy in NSCLC by longitudinal tracKing – protocol of a non-randomised, open-label, single-arm, phase II study

Article

作者: Kirchner, Marietta ; Doerr, Fabian ; Cvetkovic, Jelena ; Christopoulos, Petros ; Bölükbas, Servet ; Thomas, Michael ; Wiesweg, Marcel ; Stenzinger, Albrecht ; Eichhorn, Martin E ; Winter, Hauke ; Hegedüs, Balazs ; Schnorbach, Johannes ; Klotz, Laura V ; Schneider, Marc ; Allgaeuer, Michael ; Schramm, Alexander ; Eichhorn, Florian ; Bozorgmehr, Farastuk ; Schuler, Martin ; Griffo, Raffaella ; Roesch, Romina M

Background:

Immunotherapies targeting the programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) checkpoint have a major impact on the treatment of both resectable and advanced non-small cell lung cancer (NSCLC). Additional blockade of the T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibition motif domain (TIGIT)-receptor may synergistically foster the immune-related response. Several trials are currently investigating the combination of neoadjuvant platinum-based chemotherapy and dual checkpoint inhibition prior to curative surgery. The investigator-initiated NeoTRACK trial (EU CT number: 2022-501322-38-00; ClinicalTrials.gov identifier:NCT05825625; IKF056) aims to evaluate the feasibility and safety of perioperative anti-PD-L1 (by atezolizumab) and anti-TIGIT (by tiragolumab) treatment in combination with chemotherapy in patients with early stage NSCLC.

Methods and analysis:

NeoTRACK is an open-label, single-arm, prospective, bicentric phase II trial. Patients with NSCLC in clinical stages II, IIIA and IIIB (only T3N2) will receive two cycles of standard platinum-based chemotherapy in combination with the anti-TIGIT antibody tiragolumab and the anti-PD-L1 antibody atezolizumab, followed by curative surgery. After surgery, patients without pathological complete response (pCR) will receive another two cycles of chemotherapy in combination with tiragolumab and atezolizumab, followed by tiragolumab/atezolizumab maintenance for up to 1 year (maximum 16 cycles). Patients with pCR will only receive dual immunotherapy. All patients will be followed-up for 30 months after the last study treatment. The clinical study will be aligned with a translational research programme to investigate treatment-naïve tumour tissues, surgical specimens and longitudinally collected blood samples. 35 patients are planned for enrolment. Patient recruitment started in August 2023, and treatment of the last patient is estimated to start 2.5 years thereafter.

Discussion:

The NeoTRACK trial aims to assess the feasibility and efficacy of combining tiragolumab and atezolizumab as both neoadjuvant and adjuvant therapies in patients with resectable NSCLC. The concept of treatment personalisation based on postoperative pCR is of great clinical interest.

Ethics and dissemination:

The trial obtained ethical and regulatory approval in Germany through the Clinical Trials Information System (CTIS, ID: 2022-501322-38-00) and the Paul Ehrlich Institute (PEI, competent authority for approval of clinical trials using medicinal products for human use in Germany, process number: PB00148) on 30 March 2023. A data safety and monitoring board will meet regularly to review ongoing treatment in terms of safety.Study results will be published in peer-reviewed journals, presented at conferences and in the public registry of CTIS, following trial completion.

Trial registration number:

NCT05825625.

2025-02-01·LANCET ONCOLOGY

Tiragolumab in combination with atezolizumab and bevacizumab in patients with unresectable, locally advanced or metastatic hepatocellular carcinoma (MORPHEUS-Liver): a randomised, open-label, phase 1b–2, study

Article

作者: Yu, Nancy ; Wang, Yulei ; Hack, Stephen P ; Ryoo, Baek-Yeol ; Mahrus, Sami ; Burgoyne, Adam M ; Secrest, Matthew H ; Li, Daneng ; Yin, Anqi ; Edubilli, Tirupathi Rao ; Finn, Richard S ; Gane, Ed ; Badhrinarayanan, Shreya ; Shemesh, Colby S ; Cotter, Christopher ; Cha, Edward ; Hsu, Chih-Hung

BACKGROUND:

PD-L1 and VEGF blockade with atezolizumab plus bevacizumab has been shown to improve survival in unresectable hepatocellular carcinoma. TIGIT is an immune checkpoint regulator implicated in many cancers, including unresectable hepatocellular carcinoma. Here, we evaluate the clinical activity and safety of the addition of tiragolumab, an anti-TIGIT monoclonal antibody, to atezolizumab plus bevacizumab.

METHODS:

This randomised, open-label, phase 1b-2 umbrella study was conducted at 26 centres across China, France, Israel, New Zealand, South Korea, Taiwan, and the USA. Eligible patients were adults aged 18 years old or older with previously untreated locally advanced unresectable hepatocellular carcinoma, an Eastern Cooperative Oncology Group performance status of 0-1, Child-Pugh class A disease, and a life expectancy of at least 3 months. Eligible patients were randomly assigned (2:1) using permuted block randomisation to receive either tiragolumab 600 mg plus atezolizumab 1200 mg plus bevacizumab 15 mg/kg or atezolizumab 1200 mg plus bevacizumab 15 mg/kg, administered via intravenous infusion every 3 weeks on day 1 of each 21-day cycle. Patients received treatment until unacceptable toxic effects or loss of clinical benefit, whichever occurred first. The primary endpoint was objective response rate. Analysis of clinical activity was done in the efficacy-evaluable population (all patients who received at least one dose of each drug for their assigned treatment regimen) and safety was assessed in all patients who received any study treatment. The trial is registered with ClinicalTrials.gov, NCT04524871, and is ongoing.

FINDINGS:

Between Aug 20, 2020, and Feb 10, 2022, we assessed 154 patients for eligibility and 59 eligible patients were randomly assigned to receive tiragolumab plus atezolizumab plus bevacizumab (n=41) or atezolizumab plus bevacizumab (n=18); one patient in the tiragolumab plus atezolizumab plus bevacizumab group experienced an adverse event before receiving any treatment and withdrew from the study. Median age was 65·0 years (IQR 61·0-73·0). 46 (79%) of 58 patients were male and 12 (21%) were female. Most patients were Asian (23 [40%]) or White (21 [36%]). At the time of clinical cutoff (Aug 21, 2023), median follow-up was 20·6 months (IQR 10·6-28·0) in the tiragolumab plus atezolizumab plus bevacizumab group and 14·0 months (4·2-18·5) in the atezolizumab plus bevacizumab group. The confirmed objective response rate was 43% (95% CI 27-59, n=17) in the tiragolumab plus atezolizumab plus bevacizumab group and 11% (1-35, n=2) in the atezolizumab plus bevacizumab group. All patients in both groups experienced an adverse event. The incidence of pruritis (20 [50%] of 40 patients vs three [17%] of 18 patients), arthralgia (13 [33%] vs two [11%]), and diarrhoea (12 [30%] vs one [6%]) was notably higher in the tiragolumab plus atezolizumab plus bevacizumab group than in the atezolizumab plus bevacizumab group, although these were mainly grade 1-2. The most common grade 3-4 adverse events were hypertension (six [15%] of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group vs two [11%] of 18 patients in the atezolizumab plus bevacizumab group), aspartate aminotransferase increased (three [8%] of 40 patients vs one [6%] of 18 patients), and proteinuria (two [5%] of 40 patients vs two [11%] of 18 patients). Serious adverse events occurred in 21 (53%) of 40 patients in the tiragolumab plus atezolizumab plus bevacizumab group and in ten (56%) of 18 patients in the atezolizumab plus bevacizumab group. Treatment-related deaths occurred in one patient in the tiragolumab plus atezolizumab plus bevacizumab group (due to cholestasis) and two patients in the atezolizumab plus bevacizumab group (due to oesophageal varices haemorrhage and upper gastrointestinal haemorrhage). The addition of tiragolumab to atezolizumab plus bevacizumab did not appear to result in a substantial worsening of treatment-related or immune-mediated adverse events, and no new safety signals were identified.

INTERPRETATION:

This signal-seeking study suggests that the addition of tiragolumab to atezolizumab and bevacizumab might be more clinically active than atezolizumab plus bevacizumab alone in unresectable hepatocellular carcinoma. Based on these data, further study of combination tiragolumab plus atezolizumab plus bevacizumab is warranted.

FUNDING:

F Hoffmann-La Roche and Genentech.

322

项与替瑞利尤单抗相关的新闻（医药）

2025-07-29

·ioncology

ESMO 2025丨标题公布！消化道肿瘤领域口头报告一文速览

点击蓝字关注我们编者按2025年欧洲肿瘤内科学会年会（ESMO 2025）将于10月17~21日在德国柏林盛大举行。作为全球肿瘤学领域最具影响力的学术盛会之一，本届大会将集中呈现肿瘤诊疗领域的突破性研究进展。目前，大会官网已公布除LBA（Late-breaking Abstract）摘要外的全部入选研究标题。本文系统梳理了消化系统肿瘤领域Proffered Paper session和Mini oral session部分前沿成果，涵盖结直肠癌、胃癌、肝癌、胰腺癌、神经内分泌肿瘤等主要癌种，旨在为临床工作者和研究人员构建完整的研究进展图谱。期待ESMO 2025正式召开时，更多重磅数据的发布有望为全球消化系统肿瘤诊疗实践带来革命性突破。上消化道肿瘤Proffered Paper session 摘要号：2094O英文标题：SKYSCRAPER-07: A phase Ⅲ, randomised study of atezolizumab (atezo) with or without tiragolumab (tira) in patients (pts) with unresectable esophageal squamous cell carcinoma (ESCC) that has not progressed following definitive concurrent chemoradiotherapy (dCRT)中文标题：SKYSCRAPER-07：阿替利珠单抗（Atezo）联合或不联合Tiragolumab（Tira）治疗接受过根治性同步放化疗（dCRT）后未进展的不可切除食管鳞癌（ESCC）患者的Ⅲ期随机研究讲者：Ian Chau (Sutton, United Kingdom)Mini oral session 摘要号：2095MO 英文标题：Pembrolizumab and trastuzumab in combination with FLOT in the perioperative treatment of HER2-positive localized esophagogastric adenocarcinoma – Interim Analysis of the phase Ⅱ PHERFLOT/IKF-053 trial of the AIO study group (AIO STO 0321)中文标题：帕博利珠单抗联合曲妥珠单抗及FLOT方案用于HER2阳性局部食管胃腺癌围手术期治疗——AIO研究组Ⅱ期PHERFLOT/IKF-053试验的阶段性分析（AIO STO 0321）讲者：Eray Goekkurt (Hamburg, Germany)***************************************************************摘要号：2096MO英文标题：Systemic Therapy, Gastrectomy and CRS/HIPEC vs Systemic Therapy Alone for Gastric Cancer with Limited Peritoneal Dissemination: Results of the Randomised PERISCOPE Ⅱ Trial.中文标题：系统治疗、胃切除术联合CRS/HIPEC对比单纯系统治疗用于局限性腹膜播散胃癌：随机化PERISCOPE Ⅱ试验结果讲者：Judith S. Quik (Amsterdam, Netherlands)***************************************************************摘要号：1469MO英文标题：Liver resection versus continued atezolizumab plus bevacizumab (atezo/bev) in locally advanced hepatocellular carcinoma (HCC) after atezo/bev treatment (TALENTop): a multicenter, open-label, randomized phase Ⅲ trial.中文标题：局部晚期肝细胞癌（HCC）患者接受Atezo/Bev治疗后，肝切除术对比继续Atezo/Bev治疗（TALENTop）：多中心、开放标签、随机Ⅲ期试验讲者：Hui-Chuan Sun (Shanghai, China)讲者：复旦大学附属中山医院孙惠川***************************************************************摘要号：1470MO英文标题：Perioperative Camrelizumab plus Rivoceranib in Resectable Hepatocellular Carcinoma (CARES-009): A Randomized, Multicenter, Phase 3 Trial中文标题：围手术期卡瑞利珠单抗联合瑞戈非尼治疗可切除肝细胞癌（CARES-009）：随机、多中心、Ⅲ期试验讲者：复旦大学附属中山医院周俭***************************************************************摘要号：1471MO英文标题：Adding Ipilimumab (IPI) to Atezolizumab (ATEZO) plus Bevacizumab (BEV) in patients (pts) with unresectable hepatocellular carcinoma (uHCC) in first-line systemic therapy (1L): PRODIGE 81/FFCD 2101 - TRIPLET HCC中文标题：伊匹木单抗（IPI）联合阿替利珠单抗（ATEZO）和贝伐珠单抗（BEV）用于不可切除肝细胞癌（uHCC）的一线系统治疗（1L）：PRODIGE 81/FFCD 2101 - TRIPLET HCC试验讲者：Philippe Merle (LYON, France)***************************************************************摘要号：2214MO 英文标题：Phase 1 basket study of telisotuzumab adizutecan (ABBV-400; Temab-A), a c-Met protein–targeting antibody-drug conjugate: Results from patients (pts) with pancreatic ductal adenocarcinoma (PDAC)中文标题：针对c-Met蛋白的抗体药物偶联物Telisotuzumab Adizutecan（ABBV-400; Temab-A）的Ⅰ期篮式研究：胰腺导管腺癌（PDAC）患者的结果讲者：James J. Harding (New York, United States of America)***************************************************************摘要号：2215MO英文标题：HRS-4642 Combined with Gemcitabine and Nab-paclitaxel in KRAS-G12D Mutant Advanced Pancreatic Cancer: A Phase 1b/2 Study中文标题：HRS-4642联合吉西他滨和白蛋白结合型紫杉醇治疗KRAS-G12D突变晚期胰腺癌：1b/2期研究讲者：上海交通大学医学院附属仁济医院王理伟教授***************************************************************摘要号：2216MO英文标题：VIRAGE trial: randomized Phase Ⅱb, open-label, study of Nab-Paclitaxel and Gemcitabine with/without intravenous VCN-01 in Patients with Metastatic Pancreatic Cancer (mPDAC)中文标题：VIRAGE试验：随机Ⅱb期、开放标签研究，评估白蛋白结合型紫杉醇联合吉西他滨±静脉VCN-01治疗转移性胰腺癌（mPDAC）讲者：Rocio Garcia-Carbonero (Madrid, Spain)下消化道肿瘤Proffered paper session摘要号：726O英文标题：Prognostic value of the Combined Analysis of Pathologists and Artificial Intelligence (CAPAI) in high-risk stage Ⅱ-Ⅲ colon cancer treated without chemotherapy: interim report from a nationwide validation中文标题：病理学家与人工智能联合分析（CAPAI）对未接受化疗的高危Ⅱ-Ⅲ期结肠癌的预后价值：全国验证的阶段性报告讲者：Marie-Christine E. Bakker (Utrecht, Netherlands)***************************************************************摘要号：723O英文标题：Post-surgical liquid biopsy-guided treatment of stage Ⅲ and high-risk stage Ⅱ colon cancer patients: final results of the PEGASUS trial.中文标题：术后液体活检指导的Ⅲ期及高危Ⅱ期结肠癌治疗：PEGASUS试验最终结果讲者：Silvia Marsoni (Milan, Italy, (TO))***************************************************************摘要号：724O英文标题：Comparison of outcomes in clinical trials of locally advanced dMMR colon cancer: FOxTROT and NICHE-2中文标题：局部晚期dMMR结肠癌临床试验结果比较：FOxTROT与NICHE-2讲者：Jenny Seligmann (Leeds, United Kingdom, Yorkshire)***************************************************************摘要号：725O英文标题：Leveraging Artificial Intelligence to predict immune checkpoint inhibitor (ICI) efficacy in proficient MMR mCRC: translational analyses of AtezoTRIBE and AVETRIC trials中文标题：利用人工智能预测免疫检查点抑制剂（ICI）在MMR熟练型转移性结直肠癌（mCRC）中的疗效：AtezoTRIBE和AVETRIC试验的转化分析讲者：Martina Carullo (Pisa, Italy)Mini oral session摘要号：1MO英文标题：Placental features overexpression reveals hidden facets of early-onset colorectal cancer中文标题：胎盘特征过度表达揭示早发性结直肠癌的隐藏面讲者：Gianluca Mauri (Milan, Italy)***************************************************************摘要号：727MO英文标题：FOLFOX plus PANITUMUMAB (Pmab) according to a “stop-and-go” strategy in first-line in patients (pts) with non-mutated RAS/BRAF metastatic colorectal cancer (mCRC). Results of the FFCD 1605 – OPTIPRIME phase Ⅱ trial.中文标题： FOLFOX联合帕尼单抗（Pmab）"stop-and-go"策略治疗RAS/BRAF野生型转移性结直肠癌（mCRC）患者的一线治疗：FFCD 1605-OPTIPRIME Ⅱ期试验结果讲者：Jean-Baptiste Bachet (Paris, France)***************************************************************摘要号：728MO英文标题：Predictive Value of Low-Frequency Resistance Mutations and Relative Mutant Allele Frequencies (rMAFs) in Anti-EGFR Rechallenge for RAS/BRAF Wild-Type (wt) Metastatic Colorectal Cancer (mCRC)中文标题：低频耐药突变及相对突变等位基因频率（rMAFs）在RAS/BRAF野生型转移性结直肠癌（mCRC）抗EGFR再挑战中的预测价值讲者：Pau Mascaró Baselga (Barcelona, Spain)***************************************************************摘要号：729MO英文标题：Circulating tumor (ct) DNA analysis of BRAF V600E dynamics and changes in genomic landscape in patients (pts) with first-line (1L) BRAF V600E-mutant metastatic colorectal cancer (mCRC) treated in BREAKWATER中文标题：循环肿瘤（ct）DNA分析BRAF V600E动态及基因组图谱变化：BREAKWATER试验中一线（1L）BRAF V600E突变转移性结直肠癌（mCRC）患者讲者：Scott Kopetz (Houston, United States of America)***************************************************************摘要号：730MO英文标题：Trifluridine/Tipiracil in combination with Capecitabine and Bevacizumab as upfront treatment for metastatic colorectal cancer: first results of the phase Ⅱ TriComB study by GONO中文标题：曲氟尿苷/替匹嘧啶联合卡培他滨和贝伐珠单抗作为转移性结直肠癌的初始治疗：GONO Ⅱ期TriComB研究的初步结果讲者：Veronica Conca (Pisa, Italy)***************************************************************摘要号：731MO英文标题：Telisotuzumab adizutecan (ABBV-400; Temab-A) in combination with bevacizumab (Bev) vs standard of care (SOC) in patients (pts) with 3L+ colorectal cancer (CRC): Dose expansion results of a phase 1 study中文标题：Telisotuzumab Adizutecan（ABBV-400; Temab-A）联合贝伐珠单抗（Bev）对比标准治疗（SOC）用于3线及以上结直肠癌（CRC）：Ⅰ期研究剂量扩展结果讲者：Michael Cecchini (New Haven, United States of America)神经内分泌肿瘤与内分泌肿瘤Proffered Paper session摘要号：1705O英文标题：LITESPARK-015: Belzutifan in advanced pheochromocytoma and paraganglioma中文标题：LITESPARK-015：Belzutifan治疗晚期嗜铬细胞瘤和副神经节瘤讲者：Camilo Jimenez (Houston, United States of America)***************************************************************摘要号：1706O英文标题：Efficacy, safety and subgroup analysis of 177Lu-edotreotide vs everolimus in patients with Grade 1 or Grade 2 GEP-NETs: Phase 3 COMPETE trial中文标题：177Lu-edotreotide对比依维莫司治疗1~2级胃肠胰神经内分泌肿瘤（GEP-NETs）的疗效、安全性及亚组分析：Ⅲ期COMPETE试验讲者：Jaume Capdevila (Barcelona, Spain)***************************************************************摘要号：2987O英文标题：Efficacy and Safety of Dabrafenib Plus Trametinib (D+T) in Patients With Radioactive Iodine (RAI)-Refractory BRAF V600-Mutant Differentiated Thyroid Cancer (DTC)中文标题：达拉非尼联合曲美替尼（D+T）治疗放射性碘（RAI）难治性BRAF V600突变分化型甲状腺癌（DTC）的疗效与安全性讲者：津市人民医院高明教授Mini oral session摘要号：1707MO英文标题：A Phase 2 Dose Expansion Study of ZG006, a Trispecific T Cell Engager Targeting DLL3/DLL3/CD3, as Monotherapy in Patients with Refractoy Neuroendocrine Carcinoma中文标题：ZG006（靶向DLL3/DLL3/CD3的三特异性T细胞衔接器）单药治疗难治性神经内分泌癌的Ⅱ期剂量扩展研究讲者：中国人民解放军总医院赵传华***************************************************************摘要号：1708MO英文标题：ZG005 in combination with etoposide and cisplatin for the first-line treatment of advanced neuroendocrine carcinoma中文标题：ZG005联合依托泊苷和顺铂用于晚期神经内分泌癌的一线治疗讲者：Sisi Ye (Beijing, China)***************************************************************摘要号：1709MO英文标题：Multi-center NCI-sponsored phase 1 study of triapine in combination with 177Lu-dotatate in patients with well-differentiated gastroenteropancreatic neuroendocrine tumours (GEP-NETs)中文标题：多中心NCI资助的Ⅰ期研究：Triapine联合177Lu-dotatate治疗分化良好的胃肠胰神经内分泌肿瘤（GEP-NETs）讲者：Aman Chauhan (Deerfield Beach, United States of America)***************************************************************摘要号：1033MO英文标题：[212Pb]VMT-α-NET targeted alpha-particle therapy (TAT) for advanced somatostatin receptor 2 positive (SSTR2+) neuroendocrine tumours (NETs): mature safety and preliminary efficacy for enrollment from dose-finding cohorts 1 and 2 (n=44)中文标题：[212Pb]VMT-α-NET靶向α粒子治疗（TAT）用于晚期生长抑素受体2阳性（SSTR2+）神经内分泌肿瘤（NETs）：剂量探索队列1和2（n=44）的成熟安全性和初步疗效讲者：Thorvardur R. Halfdanarson (Rochester, United States of America)***************************************************************摘要号：1034MO英文标题：Long-term Follow-up of Peptide Receptor Radionuclide Therapy (PRRT)-Naïve Patients with Gastroenteropancreatic Neuroendocrine Tumors (GEP-NETs) Treated with Targeted Alpha Therapy 212Pb-DOTAMTATE in the Phase 2 ALPHAMEDIX 02 Trial中文标题：212Pb-DOTAMTATE靶向α治疗在未接受过肽受体放射性核素治疗（PRRT）的胃肠胰腺神经内分泌肿瘤（GEP-NETs）患者中的长期随访：一项Ⅱ期ALPHAMEDIX 02临床试验结果讲者：Jonathan R. Strosberg (Tampa, United States of America)***************************************************************摘要号：1035MO英文标题：A Prediction Tool for Malnutrition and Sarcopenia in Patients with Gastroenteropancreatic (GEP) Neuroendocrine Neoplasms (NENs): Results from NUTRIGETNE (GETNE-S2109) Study中文标题：胃肠胰神经内分泌肿瘤（NENs）患者营养不良和肌肉减少症的预测工具：NUTRIGETNE（GETNE-S2109）研究结果讲者：Maribel Del Olmo (Valencia, Spain)***************************************************************摘要号：1710MO英文标题：Belzutifan for Advanced Pancreatic Neuroendocrine Tumors (panNETs): Results From Cohort A2 of the Phase 2 LITESPARK-015 Study中文标题：Belzutifan治疗晚期胰腺神经内分泌肿瘤（panNETs）：Ⅱ期LITESPARK-015研究A2队列结果讲者：Jaume Capdevila (Barcelona, Spain)***************************************************************摘要号：2988MO英文标题：Patient-Derived Organoids Predict Clinical Response and Guide Personalized Therapy in Advanced Thyroid Cancer中文标题：患者来源的类器官预测晚期甲状腺癌临床反应并指导个性化治疗讲者：Jiaye Liu (Chengdu, China)（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。

临床2期临床3期临床结果临床成功

2025-07-26

·ioncology

新辅助治疗成新宠！2025 ASCO 黑色素瘤围术期治疗进展

编者按：2025年美国临床肿瘤学会（ASCO）已经落下帷幕，全球肿瘤学同道见证了许多重磅研究正在或即将改变临床实践。在黑色素瘤围术期治疗领域有多项研究作为延迟突破性摘要（LBA）在大会上公布，尤其术前新辅助治疗取得不少突破性进展，围绕新辅助和辅助治疗的“掰头”仍在持续升级。《肿瘤瞭望》特邀北京大学肿瘤医院斯璐教授、王稼祥医生总结和点评ASCO黑色素瘤围术期研究进展如下。01新辅助治疗随着SWOG 1801和NADINA两项新辅助临床研究结果公布，黑色素瘤进入新辅助治疗时代。相比单纯术后辅助， PD-1单抗新辅助将III期皮肤型黑色素瘤2年复发风险降低了23%；PD-1单抗联合CTLA-4单抗新辅助治疗将1年无事件生存（EFS）率提升到了83.7%（单纯辅助组57.2%），且59%的患者达到主要病理缓解（MPR）从而免去了后续长期辅助治疗[1,2]。免疫单药与联合、其他免疫检查点的应用以及其他亚型新辅助方案的探索仍是目前值得探索的方向。II期患者从单免新辅助治疗中获益有限SWOG 1801研究已经证实了帕博利珠单抗（PD-1单抗）单药新辅助在III期皮肤型患者中能显著降低复发风险，其在II期黑色素瘤患者的疗效尚需探索[1]。美国宾州大学附属医院牵头的一项II期新辅助研究评估了帕博利珠单抗在临床IIB-IIC期皮肤黑色素瘤中的应用，研究共纳入64例患者，术前帕博利珠单抗新辅助后继续辅助治疗1年。结果显示，新辅助治疗组总体前哨淋巴结（SLN）阳性率未显著降低（P=0.384）；但IIC亚组SLN阳性率降低了23.3%（P=0.009）。中位随访20.4个月时，2年无复发生存率（RFS）为81%，远处无转移生存率（DMFS）88%。该研究2年RFS率与KEYNOTE 716（81.2%）和CHECKMATE 76K（78%）结果类似[3,4]。三药联合为肢端新辅助带来新变革替莫唑胺联合阿帕替尼及卡瑞丽珠单抗的三药联合方案已在晚期肢端黑色素瘤一线治疗中取得了较好效果（ORR 64%，中位PFS 18.4个月）[5]。同样由该团队主导的CAP 03-NEO II期研究创新性地采用两阶段设计，评估了卡瑞利珠单抗联合阿帕替尼及替莫唑胺三药联合方案在可切除II/III期肢端型黑色素瘤新辅助治疗中的疗效。研究纳入30例患者（II期11例，III期19例），28例接受手术的患者中病理缓解率达57.1%（含7例pCR和5例near-pCR），III期患者的MPR率显著高于II期（42.9% vs 36.7%）。中位随访18.1个月显示，12个月EFS率达77.6%（III期患者75%），达到MPR的患者1年EFS率为100%。更多双免联合方案证据及探索2024年公布的III期临床研究数据，纳武利尤单抗（NIVO）联合伊匹木单抗（IPI）在III期黑色素瘤新辅助治疗中降低了26.5%的1年复发风险，pCR（病理完全缓解）率达到了47.2%，MPR的患者1年RFS（无复发生存）率达到了95.1%[2]。今年ASCO大会上，同样是NIVO+IPI新辅助的II期C-IT Neo trial研究报道了相似的结果，pCR率达45.4%，MPR患者1年RFS率为100%，但此研究仅纳入了22例患者。更多免疫检查点抑制剂联合方案在新辅助中的疗效也在探索中。在美国开展的II期临床试验NeoACTIVATE的Arm C队列中，阿替利珠单抗（PDL-1单抗）联合tiragolumab（TIGIT单抗）的双免疫疗法在III期高危可切除黑色素瘤患者新辅助中pCR率达38.2%，1年EFS率72%，1年RFS和DMFS分别为73.3%和86%。另一项III期随机非对照新辅助NEO-MEL-T研究对比Dostarlimab（PD-1单抗）单药新辅助同Dostarlimab+Cobolimab（TIM-3单抗）联合新辅助的效果，对比Dostarlimab单药新辅助，联合新辅助组的pCR率仅提高了3.7%（37% vs 33.3%），但MPR率提高了22.3%（55.6% vs 33.3%），影像评估中ORR（客观缓解率）提高了1倍（33.3% vs 16.7%），不过两组中位RFS无显著差异。点评黑色素瘤新辅助治疗近年来备受关注，免疫单药或联合的选择是目前皮肤型黑色素瘤探索的方向之一。PD-1单抗新辅助在II期皮肤型黑色素瘤中整体呈阴性结果，但IIC期患者SLN阳性率显著降低，双免疫新辅助方案中，PD-1单抗+CTLA-4单抗的联合方案相较于其他免疫检查点抑制剂的联合似乎更能降低复发转移风险。三药联合方案在肢端亚型中取得了和双免在皮肤型新辅助中类似的MPR率，为中国黑色素瘤新辅助治疗方案提供了参考。如何能在降低复发转移风险的同时延长OS，是未来新辅助研究应该关注及解决的问题。02辅助治疗目前NCCN指南已将PD-1单抗及达拉非尼+曲美替尼双靶方案作为III期皮肤型黑色素瘤辅助治疗推荐，II期患者是否也能达到相似的获益，免疫联合辅助治疗方案能否使患者进一步获益，以及其他分型黑色素瘤的辅助治疗模式的探索是值得关注的方向。双免辅助未优于单免辅助2024年ESMO大会上公布了KEYNOTE 054的7年随访结果，PD-1单抗单药辅助可降低III期皮肤型黑色素瘤14%的复发风险（PD-1单抗50% vs安慰剂组36%）。但双免是否能进一步降低复发风险，为此，RELATIVITY 098研究在III-IV期黑色素瘤开展了LAG3单抗Relatilimab联合Nivolumab对比Nivolumab单药辅助的多中心3期临床试验，经中位随访26.7个月后，两组RFS无显著差异。NIVO+RELA和NIVO单药组的1年RFS率分别为75%和72%，2年RFS率62%和64%。双靶方案在II期辅助中安全性探索达拉非尼联合曲美替尼在BRAF突变的III期皮肤黑色素瘤辅助中可降低32%的1年复发风险（1年RFS 88% vs 安慰剂56%），4年RFS率提升了16%（54% vs 38%）[6,7]。在II期BRAF-V600E/K突变皮肤型患者中，今年ASCO大会中的EORTC-2139-MG/Columbus-AD III期研究显示，BRAF抑制剂Encorafenib联合MEK抑制剂Binimetinib（E+B）辅助治疗的1年RFS率提升了16%（86% vs 70%），DMFS率为92%（安慰剂组82%）。尽管安全性可控（3级以上毒性24%），但因PD-1单抗在同类适应症中的优先获批（如KEYNOTE-716的1年RFS 90%），该研究提前终止，仅入组110例患者，最终转为安全性探索性分析。点评今年黑色素瘤辅助研究结果多为阴性，对阴性结果原因的探讨或许能为未来的研究提供思考。RELATIVITY 098中NIVO联合RELA辅助相较于NIVO单药并未显著降低复发风险，进一步T细胞亚群变化分析提示晚期患者LAG-3+ T细胞水平更高且治疗后 LAG-3+ T 细胞的增加较辅助患者更为显著。这或许可以说明肿瘤存在的时候具有更强的免疫原性，因此可能可以解释在晚期治疗RELATIVITY-047中免疫联合治疗效果更佳。Columabus-AD的双靶辅助研究无疾而终，但对于呈独特的“冷肿瘤”特征的中国黑色素瘤，靶向辅助治疗或许仍有望成为后续辅助治疗探索方向之一。随着新辅助研究中MPR率的不断提高，根据不同的病理缓解率来设计后续辅助治疗方案将成为未来辅助治疗的趋势。参考文献上下滑动查看更多内容[1].Patel SP, Othus M, Chen Y, Wright GP, Jr., Yost KJ, Hyngstrom JR, Hu-Lieskovan S, Lao CD, Fecher LA, Truong TG et al: Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma. N Engl J Med 2023, 388（9）:813-823.[2].Blank CU, Lucas MW, Scolyer RA, van de Wiel BA, Menzies AM, Lopez-Yurda M, Hoeijmakers LL, Saw RPM, Lijnsvelt JM, Maher NG et al: Neoadjuvant Nivolumab and Ipilimumab in Resectable Stage III Melanoma. N Engl J Med 2024, 391（18）:1696-1708.[3].Luke JJ, Rutkowski P, Queirolo P, Del Vecchio M, Mackiewicz J, Chiarion-Sileni V, de la Cruz Merino L, Khattak MA, Schadendorf D, Long GV et al: Pembrolizumab versus placebo as adjuvant therapy in completely resected stage IIB or IIC melanoma （KEYNOTE-716）: a randomised, double-blind, phase 3 trial. Lancet 2022, 399（10336）:1718-1729.[4].Kirkwood JM, Del Vecchio M, Weber J, Hoeller C, Grob JJ, Mohr P, Loquai C, Dutriaux C, Chiarion-Sileni V, Mackiewicz J et al: Adjuvant nivolumab in resected stage IIB/C melanoma: primary results from the randomized, phase 3 CheckMate 76K trial. Nat Med 2023, 29（11）:2835-2843.[5].Mao L, Lian B, Li C, Bai X, Zhou L, Cui C, Chi Z, Sheng X, Wang X, Tang B et al: Camrelizumab Plus Apatinib and Temozolomide as First-Line Treatment in Patients With Advanced Acral Melanoma: The CAP 03 Phase 2 Nonrandomized Clinical Trial. JAMA Oncol 2023, 9（8）:1099-1107.[6].Hauschild A, Dummer R, Schadendorf D, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C et al: Longer Follow-Up Confirms Relapse-Free Survival Benefit With Adjuvant Dabrafenib Plus Trametinib in Patients With Resected BRAF V600-Mutant Stage III Melanoma. J Clin Oncol 2018, 36（35）:3441-3449.[7].Long GV, Hauschild A, Santinami M, Atkinson V, Mandalà M, Chiarion-Sileni V, Larkin J, Nyakas M, Dutriaux C, Haydon A et al: Adjuvant Dabrafenib plus Trametinib in Stage III BRAF-Mutated Melanoma. N Engl J Med 2017, 377（19）:1813-1823.斯璐教授北京大学肿瘤医院黑色素瘤及肉瘤内科，主任医师，博士生导师《CSCO黑色素瘤诊治指南》执笔人《CSCO免疫检查点抑制剂相关毒性管理指南》执笔人CSCO黑色素瘤专家委员会副主任委员CSCO神经系统肿瘤专委会副主任委员《肿瘤学杂志》青年编委、副主编Clinical Cancer Research审稿专家王稼祥北京大学临床肿瘤学院肿瘤内科博士北京大学肿瘤医院肾癌黑色素瘤内科住院医师主要研究方向：黑色素瘤的靶向、免疫、化疗等综合治疗（来源：《肿瘤瞭望》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。

ASCO会议临床结果临床3期临床2期

2025-07-25

·E药经理人

罗氏血亏，百济叫停，MNC全员撤退！明星赛道沦为“天坑”，发生了啥？

从早期单药无效的挫折，到最终在III期联合临床试验中全面溃败，TIGIT靶点兵败如山倒，到底哪出错了？撰文| 润屿TIGIT研发领域，痛失最后一位、也是坚守最久的超级大“玩家”——罗氏。7月24日，罗氏发布了2025年半年报，同时宣布砍掉7大研发管线，包括四项I期和三项III期临床研究。其中，其全球首个进入III期的TIGIT抑制剂——RG6058（tiragolumab）仅剩的两项III期临床，已经正式终止。自2022年起，该产品III期研究接连碰壁，2024年Q4罗氏披露管线进展时，涉及该产品2项III期、2项II期及1项I期临床研究悉数被砍，占了所有“断舍离”管线的一半；今年Q1罗氏进一步终止其联合Tecentriq治疗局部晚期食管癌的III期研究。而伴随最后两项III期临床的终止，RG6058的10年研发历程彻底画上句点，这也标志着罗氏在TIGIT赛道长达数年的探索与苦撑，全然打了水漂。曾经，TIGIT 靶点凭独特的免疫调节机制，被业界寄予厚望，认为它将成为继 PD-1/PD-L1 之后又一个改写肿瘤治疗格局的 “黄金靶点”。罗氏、GSK、BMS、诺华等众多药企纷纷重金投入，PD-1“四小龙”等中国药企亦开启了一场激烈的研发竞赛。然而，现实却如同一场残酷的风暴，从罗氏丢掉重要城池开始，几乎所有重磅玩家都已撤退离场。这背后，到底隐藏了哪些关于科学探索的艰难与无奈？罗氏：从不死心，到心已死罗氏基因泰克是最早入局TIGIT赛道的企业，在这一靶点的探索上堪称先驱。TIGIT的发现之旅始于罗氏基因泰克实验室。2002年，科学家团队首次在T细胞和NK细胞中发现一种特异性表达基因，并观察到其在免疫调节中的潜在作用，但这个新分子当时并未引发足够关注。2009年，肿瘤免疫学家Jane Grogan团队率先通过小鼠实验证实TIGIT是抑制T/NK细胞活性的关键分子。最初，这项突破聚焦于哮喘、红斑狼疮等自免疾病领域，后发现TIGIT在抗肿瘤CD8+T细胞上异常高表达，在人类肺癌组织和小鼠模型中取得了突破性发现：TIGIT不仅抑制CD8+T细胞活性，其作用机制更与PD-L1存在功能相似性。2014年，基因泰克正式公布研究成果，恰逢PD-1掀起肿瘤免疫治疗革命，TIGIT迅速与LAG-3、TIM-3并列为下一代明星靶点。罗氏于2016年率先启动了TIGIT抗体tiragolumab的I期临床。默沙东紧随其后于同年12月推进了TIGIT抗体MK7684的临床研究。2020年ASCO大会上，罗氏公布了tiragolumab联合PD-L1将晚期肺癌患者客观缓解率明显提升、让无进展生存期翻倍的数据，亮眼数据激发了行业热情。正逢PD-1疗法面临响应率有限、耐药性等瓶颈，TIGIT联合疗法成为了破局希望。罗氏趁热打铁，旋即启动了多项大Ⅲ期研究，诸多药企也于2020年和2021年扎堆入场。然而，2022年，罗氏首次迎来了TIGIT 研发路上的重大滑铁卢时刻：先是最想突破的小细胞肺癌适应证，翻车了。罗氏宣布tiragolumab联用PD-L1 治疗小细胞肺癌的III期临床失败。接着，市场对TIGIT联合疗法最给予厚望的一项适应证——非小细胞肺癌的III期试验，也没有达到PFS主要终点。“领头羊”的接连失败，让TIGIT之路陡生不确定性。但这时候的罗氏，还没有轻易放弃，他仍将其列入了2023年值得关注的研发计划中。然而，命运并不打算眷顾TIGIT。2024年7月，罗氏tiragolumab在转移性非鳞状非小细胞肺癌II/III期研究上折戟，原因是无法跟对照组拉开疗效差距。换句说，没能打败“K药”。4个月后，该产品联合PD-L1 抗体治疗局部复发性或转移性非小细胞肺癌的III期临床也未达到 OS 主要终点。而到现在，罗氏已全面撤离了这个曾经寄予厚望的赛道，转而聚焦于其他新领域。能够看到，罗氏在TIGIT上的研发策略有一大共性：联合用药是核心方向，尤其以PD-1/L1联合疗法为基石；适应证高度集中，肺癌（尤其是非小细胞肺癌）为最主要的战场。这样的策略一度掀起了业内跟风潮流，大至营收TOP10里的MNC，小至明星Biotech，几乎都选择了与罗氏类似的研发大方向，再在此基础上进行靶点组合多样化拓展。所以毫无疑问，当罗氏这一“弄潮儿”数次失利，后继者的市场信心，必然会逐渐塌缩。推荐阅读 * 强生、诺华撤退，吉利德屡败，GSK百亿杀入研发黑洞，能成吗？* 罗氏杀回第一，诺和诺德进前十，肿瘤难独霸，自免、代谢大爆发。2024哪些新药值得关注？巨头败走，“四小龙”哑火10年时间，面向几项大适应证的数项大III期临床——罗氏对TIGIT 靶点算是绝对的真爱，但也一直是负重前行，烧掉的资金不计其数。最具曙光的那一年——2021年，罗氏针对tiragolumab开展了20多项临床试验，其中包括以Skyscraper项目（主要面向肺癌）为代表的八项关键性研究。有数据显示，截至2021年6月，tiragolumab的净现值已经达到59.51亿美元。次年5月，tiragolumab相关研究入组患者的人数已超8000，可见罗氏的重视程度。2021年，更是众巨头入局、竞争角逐白热化的高光时刻。仅在那一年里，BMS斥资15.6亿美元引进TIGIT双抗；GSK以21亿美元押注iTeos公司的EOS-448；吉利德以7.5亿美元收购Arcus的几款TIGIT管线；诺华以最高28亿美元引进百济神州TIGIT抗体。当时，TIGIT在国内也获得了在PD-1竞争中占得先机的中国药企的重视——PD-1“四小龙”均有布局，另康方生物、百奥泰等多家药企亦较早入局。其中，百济率先开展了III期非小细胞肺癌研究，信达生物亦领跑国内临床。然而，罗氏的接连失利，犹如推倒了多米诺骨牌，在行业内引发了连锁反应。众多药企在 TIGIT 靶点研发上纷纷遭遇挫折，开始重新审视这条曾经被热捧的赛道。2023年，BMS终止了TIGIT 单抗的Ⅱ期临床试验，原因是在联合用药时观察到了毒性。默沙东同样未能在 TIGIT 赛道上幸免。2024年，因为免疫副作用，默沙东停止了K药与 TIGIT联用辅助治疗黑色素瘤的III期临床。仅3个月后，默沙东再次终止了K药联合TIGIT 用于一线治疗小细胞肺癌的III期临床。同年，Coherus终止了与君实生物重组人源化抗TIGIT单抗的许可合作。2025年，市场里剩下的大玩家们开始“清场”。4月，百济宣布终止 TIGIT抗体欧司珀利单抗（Ociperlimab）的肺癌适应证临床开发，因试验的总体有效性和安全性数据评估表明，该研究或难以达到总生存期主要终点，也未发现新的安全信号。5月，GSK宣布停止开发收购而来的TIGIT抗体药物——belrestotug，两周后，合作公司iTeos宣布逐步停止运营、出售资产，其累计融资11亿美元中超5亿美元化为了研发损耗。如此溃败的局面，上一次出现还是在2014年的IDO抑制剂身上。曾经被视为 “下一个 PD-1” 的TIGIT靶点，为何会陷入这一潦倒的死局？站在底层技术逻辑来看，TIGIT靶点的研发困境根源与IDO抑制剂颇为相似：单药无效，与PD-1药物联用显示一定早期疗效，但基于机制的高度复杂性，在肿瘤中的作用原理并不清楚，到了临床III期，各项研究相继出现后劲不足的情况。TIGIT与其配体形成了独特的“多对多”关系网络，作用机制至今未完全阐明，这埋下了“先天不足”的隐患。临床实践中，罗氏的TIGIT单药的临床疗效极其有限（早期单药治疗非小细胞肺癌ORR为0），基于此，罗氏很快战略性转移了研发策略——全力押注联合疗法。但后来的故事行业皆知，罗氏及一众药企的诸多关键III期试验，都失败了。一直到如今TIGIT走出聚光灯，其棘手的底层机制问题还是没有解决：TIGIT、CD226、PVR构成动态平衡网络，阻断TIGIT可能引发CD226的代偿抑制效应，犹如“按下葫芦浮起瓢”，使抗体调控失效。此外，盲目沿用PD-L1作为入组标准，而忽略TIGIT可能依赖未知且难测的生物标志物，导致试验难以精准筛选获益人群。早期寄予厚望的“1+1>2” PD-1联用协同效应，也被证明可能是PD-1效果掩盖了TIGIT的乏力。也因此，数十亿投入与稀疏的阳性数据形成鲜明反差。雷声大，雨点小。TIGIT的溃败为行业敲响警钟：面对复杂机制未清的靶点，即便联合策略与巨额资本加持，也难以绕过科学认知的鸿沟。失败的教训虽沉重，但也促使科学界更精准地探索疾病机制，为未来寻找真正有效的治疗铺路。一审| 黄佳二审| 李芳晨三审| 李静芝精彩推荐大事件 | IPO | 融资&交易 | 财报季 | 新产品 | 研发日 | 里程碑 | 行业观察 | 政策解读 | 深度案例 | 大咖履新 | 集采&国谈 | 出海 | 高端访谈 | 技术&赛道 | E企谈 | 新药生命周期 | 市值 | 新药上市 | 商业价值 | 医疗器械 | IND | 周年庆大药企 | 竞争力20强 | 恒瑞 | 石药 | 中生制药 | 齐鲁 | 复星 | 科伦 | 翰森 | 华润 | 国药 | 云南白药 | 天士力 | 华东 | 上药创新药企 | 创新100强 | 百济 | 信达 | 君实 | 复宏汉霖 | 康方 | 和黄 | 荣昌 | 亚盛｜康宁杰瑞｜贝达｜微芯｜再鼎｜亚虹跨国药企｜ＭＮＣ卓越｜辉瑞｜AZ｜诺华｜罗氏｜BMS｜默克｜赛诺菲｜GSK｜武田｜礼来｜诺和诺德｜拜耳供应链｜赛默飞｜药明｜凯莱英｜泰格｜思拓凡｜康龙化成｜博腾｜晶泰｜龙沙｜三星启思会 | 声音·责任 | 创百汇 | E药经理人理事会 | 微解药直播 | 大国新药 | 营销硬观点 | 投资人去哪儿 | 分析师看赛道 | 药事每周谈 | 中国医药手册

临床1期临床3期ASCO会议临床结果临床终止

100 项与替瑞利尤单抗相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D11482	-	-	DB16409

研发状态

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适应症	最高研发状态	国家/地区	公司	日期
胃食管交界处癌	临床3期	中国	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	日本	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	比利时	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	加拿大	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	哥斯达黎加	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	法国	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	墨西哥	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	俄罗斯	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	韩国	F. Hoffmann-La Roche Ltd.	2025-05-28
胃食管交界处癌	临床3期	中国台湾	F. Hoffmann-La Roche Ltd.	2025-05-28

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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


NCT04294810 (SKYSCRAPER-01, AACR2025) 人工标引	临床3期	非小细胞肺癌一线 PD-L1-high	534	TiragolumabTiragolumab 600 mg IV + Atezolizumab 1200 mg IVAtezolizumab 1200 mg IV	膚積壓簾糧餘繭遞膚觸(淵鏇築糧遞繭襯膚網觸) = 鑰範積糧襯襯範窪艱夢憲齋鬱選顧窪鬱鑰觸衊 (餘鏇淵膚觸夢齋艱繭製, 5.6 ~ 9.8) 更多	不佳	2025-04-28
				Placebo + Atezolizumab 1200 mg IVAtezolizumab 1200 mg IV	膚積壓簾糧餘繭遞膚觸(淵鏇築糧遞繭襯膚網觸) = 鏇繭築觸製遞簾憲淵夢憲齋鬱選顧窪鬱鑰觸衊 (餘鏇淵膚觸夢齋艱繭製, 4.4 ~ 7.0) 更多
NCT04300647 (SKYSCRAPER-04, CTgov)	临床2期	PD-L1阳性宫颈癌	172	Atezolizumab (Atezolizumab)	鑰願糧齋廠簾膚壓衊齋 = 餘膚積願糧顧膚鹽選構夢壓蓋膚網鏇淵艱選獵 (簾範鹽淵鬱窪鹹齋鏇衊, 積顧齋選觸鬱顧範鏇顧 ~ 製壓衊膚糧襯鹽觸鹽顧) 更多	-	2025-02-07
				Atezolizumab+Tiragolumab (Tiragolumab Plus Atezolizumab)	鑰願糧齋廠簾膚壓衊齋 = 獵蓋繭壓範築齋願鏇夢夢壓蓋膚網鏇淵艱選獵 (簾範鹽淵鬱窪鹹齋鏇衊, 獵願餘膚築鹽鏇艱顧選 ~ 壓蓋襯構範鑰糧夢獵繭) 更多
NCT04524871 (MORPHEUS-Liver, Pubmed \| Lancet Oncol) 人工标引	临床1/2期	肝细胞癌	58	TiragolumabTiragolumab 600 mg + Atezolizumab 1200 mg + Bevacizumab 15 mg/kgBevacizumab 15 mg/kg	積艱淵艱糧製構膚簾顧(選襯繭築膚繭遞遞齋選) = The incidence of pruritis (20 [50%] of 40 patients vs three [17%] of 18 patients), arthralgia (13 [33%] vs two [11%]), and diarrhoea (12 [30%] vs one [6%]) was notably higher in the tiragolumab plus atezolizumab plus bevacizumab group than in the atezolizumab plus bevacizumab group, although these were mainly grade 1-2. 壓廠艱觸膚艱鏇艱夢壓 (顧艱膚築艱襯糧壓簾願 ) 更多	积极	2025-01-21
				Atezolizumab 1200 mg + BevacizumabBevacizumab 15 mg/kg
NCT04619797 (SKYSCRAPER-06, ESMO_IO2024) 人工标引	临床2/3期	晚期肺非鳞状非小细胞癌维持	542	Tiragolumab 600 mg IV + Atezolizumab 1200 mg IV + Carboplatin/Cisplatin + Pemetrexed IV	積鹹膚壓糧蓋簾夢製憲(願鹽鏇鏇艱窪襯鬱選範) = 夢窪齋窪蓋願衊獵鬱獵膚鹹齋廠廠餘網獵糧簾 (製餘夢襯艱憲鬱觸糧遞, 15.2 ~ 23.8) 更多	不佳	2024-12-12
				Placebo + Pembrolizumab 200 mg IV + Carboplatin/Cisplatin + Pemetrexed IV	積鹹膚壓糧蓋簾夢製憲(願鹽鏇鏇艱窪襯鬱選範) = 網壓糧餘齋壓齋鬱淵鬱膚鹹齋廠廠餘網獵糧簾 (製餘夢襯艱憲鬱觸糧遞, 20.7 ~ 33.0) 更多
NCT04294810 (SKYSCRAPER-01, GlobeNewswire) 人工标引	临床3期	PD-L1阳性非小细胞肺癌 PD-L1 High Expression	534	tiragolumab + Tecentriq	窪網齋鏇衊簾鬱選鏇積(鏇膚觸糧範鏇襯艱夢憲) = did not reach the primary endpoint. 顧積蓋積顧積糧鏇鏇膚 (構憲夢廠觸廠餘艱構廠 ) 未达到更多	不佳	2024-11-26
				Placebo + Tecentriq
NCT05315713 (CTgov)	临床1/2期	滤泡性淋巴瘤 \| 难治性B细胞淋巴瘤	8	Mosunetuzumab SC+Tocilizumab+Tiragolumab	獵鏇遞醖齋選膚積獵選 = 範築願齋簾鏇膚艱窪憲鹽願鬱選鹽構齋鏇獵齋 (夢獵範膚淵廠壓襯糧選, 鑰淵觸構廠膚窪艱積齋 ~ 憲繭鏇夢膚鏇獵廠顧醖) 更多	-	2024-10-04
NCT04619797 (SKYSCRAPER-06, Company_Website) 人工标引	临床2/3期	转移性非鳞状非小细胞肺癌一线	542	tiragolumab+Tecentriq+chemotherapy	觸膚淵憲淵簾廠鹽鏇觸(願餘願艱齋構製壓襯醖): HR = 1.27 (95% CI, 1.02 ~ 1.57) 未达到更多	不佳	2024-07-03
				Placebo+pembrolizumab+chemotherapy
NCT04300647 (SKYSCRAPER-04, AACR2024)	临床2期	宫颈癌 PD-L1+ \| TIGIT \| TAP ... 更多	171	Tiragolumab plus atezolizumab dual blockade (T+A)	築積範獵鏇憲積膚築選(顧憲蓋構積製鹽顧膚積) = 齋構簾製膚衊廠積遞簾鏇淵醖襯獵餘壓範壓鹹 (製製獵廠廠製鹹鹽淵鬱 )	积极	2024-03-22
NCT04256421 (SKYSCRAPER-02, Pubmed) 人工标引	临床3期	广泛期小细胞肺癌一线 \| 维持	490	Tiragolumabatezolizumabcarboplatinetoposide	廠膚製製鹹顧顧壓襯願(憲鬱膚積膚鏇網鑰壓糧) = 鹽積積淵顧簾願獵獵繭淵顧鑰簾鬱淵糧構襯觸 (觸夢憲窪夢壓製選衊淵 ) 更多	不佳	2024-01-20
				AtezolizAtezolizumabrbocarboplatinetoetoposideE)	廠膚製製鹹顧顧壓襯願(憲鬱膚積膚鏇網鑰壓糧) = 壓築蓋襯餘夢繭製製繭淵顧鑰簾鬱淵糧構襯觸 (觸夢憲窪夢壓製選衊淵 ) 更多
NCT03281369 (MORPHEUS-EC, ASCO_GI2024) 人工标引	临床1/2期	食管癌一线	152	Cisplatin + 5-FU	獵淵選網鹽鏇選積網繭(範製網襯繭鹹醖獵積鹽) = 願網鹽簾簾襯襯憲鹹蓋簾憲選窪艱築築製鹽簾 (餘壓蓋鹹觸願願遞鹹齋, 26.8 ~ 69.4) 更多	积极	2024-01-18
				Atezolizumab + Cisplatin + 5-FU	獵淵選網鹽鏇選積網繭(範製網襯繭鹹醖獵積鹽) = 廠構鹽餘憲齋窪糧獵顧簾憲選窪艱築築製鹽簾 (餘壓蓋鹹觸願願遞鹹齋, 41.0 ~ 66.3) 更多