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2025-08-22

申办/合作机构

National Cancer Institute

NCT07038915

/ Withdrawn临床2期IIT

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2025-07-28

申办/合作机构

The University of Texas MD Anderson Cancer Center

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临床结果

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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）

2025-08-01·Journal for ImmunoTherapy of Cancer

Pharmacological and structural characterization of vibostolimab, a novel anti-TIGIT blocking antibody for cancer immunotherapy

Article

作者: Blumenschein, Wendy ; Keenan, Tanya ; Chien, Ellen ; Chakravorty, Srishti ; Fayadat-Dilman, Laurence ; Seghezzi, Wolfgang ; Ban, David ; Pradhan, Komal ; McCoy, Mark A ; Bahmanjah, Soheila ; Wilson, Douglas ; Yuan, Jing ; Williams, Sybil M G ; Baker, Jeanne ; Wong, Janica C ; Beaumont, Maribel ; Grein, Jeffery ; Malashock, Daniel ; Hsieh, Mark ; Fischmann, Thierry O ; Mayhood, Todd ; Han, Jin-Hwan ; Ahn, Eunseon ; Wang, Hongmei ; Cai, Mingmei

Background:

Vibostolimab is a humanized anti-T cell immunoreceptor with immunoglobulin (Ig) and ITIM domains (TIGIT) antibody was recently investigated in late-stage clinical trials. Vibostolimab was developed based on its specific binding property to the human and cynomolgus monkey TIGIT protein and its functional blocking activity of the TIGIT:CD155 interaction.

Methods:

The biochemical properties of vibostolimab, in a comparison with tiragolumab, were assessed with Biacore, nuclear magnetic resonance (NMR), and X-ray crystallography, while the T-cell activation was examined using engineered Jurkat cells in an in vitro co-culture system by measuring interleukin (IL)-2 production as a readout of T-cell activation. The mouse surrogate anti-TIGIT antibodies were identified and used to extensively investigate the mechanism of action of anti-TIGIT antibodies as monotherapy or in combination with anti-programmed cell death protein-1 (PD-1) antibody in vivo by gene expression profiling and flow cytometry analyses with a mouse syngeneic tumor model.

Results:

Structural analyses with solution NMR and X-ray crystallography revealed that vibostolimab binds the CC’C’’FG loop interface of TIGIT, completely competing for the binding site of CD155 with a larger coverage area than another anti-TIGIT antibody tiragolumab, consistent with surface plasmon resonance analysis, though mouse models with similar antibodies revealed no functional difference in antitumor efficacy. Biacore-based binding data indicate that both vibostolimab and tiragolumab bind on TIGIT with comparable binding affinity (KD), but different binding kinetics characterized by faster on and off rates, which may contribute to enhanced T-cell activation with vibostolimab, as evidenced by greater IL-2 production in an in vitro cell-based assay. Functional experiments in mouse models demonstrated additional detailed biological mechanisms of the mouse equivalent of vibostolimab, including the differentiating role of myeloid cell activation in addition to improved T cell cytolytic activity, both of which are further enhanced by anti-PD-1 combination therapy.

Conclusions:

Vibostolimab is a novel anti-TIGIT antibody that completely blocks CD155 binding and induces T-cell activation. From experiments using a mouse tumor model and mouse surrogate anti-TIGIT antibody, we demonstrate direct evidence where it not only activates cytotoxic T cells but also induces the activation of antigen-presenting cells. The clinical relevance of vibostolimab, based on these mechanisms, in combination with pembrolizumab was recently tested in registrational trials.

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.

325

项与替瑞利尤单抗相关的新闻（医药）

2025-08-11

·氨基观察

失利的TIGIT，至少烧掉了百亿

氨基观察-创新药组原创出品作者 | 武月肿瘤免疫研发的狂热与理性之殇，在TIGIT身上暴露无遗。被视为“下一代PD-1”的TIGIT靶点，在吞噬药企十几亿美元首付款和数十亿研发资金后，终成肿瘤免疫领域又一大“研发黑洞”。尽管仍有一些项目在推进临床，但在业内看来，随着今年上半年iTeos的TIGIT+PD-1联合疗法临床失败，罗氏TIGIT终止全部三期临床，TIGIT单药或联合用药全军覆没，TIGIT这一靶点基本宣告“剧终”。药物研发失败并不奇怪，这本就是一项成本高昂、风险高的业务。在药物最终上市之前，谁也无法预测最终的结果，即便是身经百战的大药企们。然而，多个临床表现与预期之间产生的不可弥合的背离，一次次失利烧掉百亿，TIGIT的大溃败仍是让我们再次见识到热门靶点的“杀伤力”，以及免疫系统的复杂性。更重要的是，TIGIT之后，下一场豪赌早已开场。如何避免重蹈覆辙，或许是所有入局者要考虑的。 / 01 / TIGIT的沉没成本 2020年，TIGIT靶点顶着“下一个PD-1”的名头横空出世。罗氏的TIGIT单抗Tiragolumab在当年ASCO大会上惊艳亮相后，吉利德、BMS、GSK、诺华等大药企开始争相入场，疯抢全球TIGIT在研临床管线，相关交易首付款超14亿美元。其中，吉利德、GSK出手最为大方，前者为了引进Arcus管线，除了支付1.75亿美元首付款（多靶点），2.75亿美元行权费（TIGIT靶点），还通过7.4亿美元股权投资（均价27.58美元/股），而Arcus股价现已跌破 10美元。 GSK为了引进iTeos的管线，仅首付款就高达6.25亿美元。随着今年5月双方因TIGIT+PD-1联合疗法临床失败而终止合作，GSK当初的首付款也打了水漂。这是我们能看到的成本。考虑到全球有超80条TIGIT管线，大药企曾先后启动大规模三期临床，以及一些biotech也借此完成了融资，整个行业在TIGIT靶点上的投入，远不止这些。首先是与BD交易相关的里程碑款超 50亿美元，但因项目终止，绝大多数未被支付。大头则是研发成本。对于罗氏等大药企来说，TIGIT的成本隐含在推进候选药物的巨额研发预算中，我们无法得知具体投入，但通过一些合作管线的投入，仍可以窥得一二。以GSK与iTeos的合作为例，GSK承诺为后者的TIGIT药物全球开发计划投入9亿美元，实际因2期失败可能仅支出小部分。但这一数字，可以为大型后期临床的投入量级提供一定参考。由于对创新免疫疗法的迫切渴望，大药企在TIGIT管线的投入规模与推进速度层面，可以说不遗余力。罗氏的tiragolumab在10项三期研究中，招募目标是近4600名患者；默沙东的vibostolimab在5项三期研究中，招募目标是超4600名患者；吉利德、Arcus等合作的3项三期研究，招募了近3000名患者。如果参照GSK与iTeos的合作投入，罗氏、吉利德、默沙东在TIGIT资产的中后期临床试验中，可能合计已经消耗掉数十亿美元。另外，iTeos的资金消耗速度，也能为我们提供一个角度。2021年以来，其通过融资及与GSK的交易，募集了超11亿美元，随着管线失败公司计划解散运营，现金储备仅剩 6.24亿美元，也就是说超5亿美元融资化为iTeos研发损耗。总之，尽管仍有一些项目在推进临床，但是随着越来越多临床失败、药企的撤退，意味着短短几年间，行业已为TIGIT投入了数十亿美元的沉没成本。 / 02 / 溃败背后正如前文所说，TIGIT靶点之所以成为研发热点，很大一部分原因与PD-1有关。当时市场都在寻找下一个PD-1，而TIGIT在免疫抑制的机制上与之有一定的相似性，但作用的细胞类型和具体环节存在差异，二者联用有可能产生协同的免疫激活效果。然而，理论与现实，总是有巨大的鸿沟。在实际临床试验中，这种联合治疗的优势并没有充分体现，单药治疗效果与PD-(L)1单药治疗相比也相差甚远。以前文提及的iTeos为例，尽管其TIGIT与PD-1联合疗法曾在非小细胞癌中取得突破，主要终点客观缓解率（ORR）达到60%以上，对照组PD-1单药仅28.1%，但今年5月其更新的数据显示，与PD-1单药治疗相比，联合疗法队列中未达到无进展生存期的既定标准。先驱罗氏则在二季度中，彻底移除了Tiragolumab。尽管TIGIT联合疗法在肝癌二期中持续更新积极数据，但二季度，其将TIGIT联合PD-L1抗体的不可切除的非小细胞肺癌，TIGIT、PD-L1抗体和贝伐珠一线肝癌的三联疗法的两项三期临床移除管线，Tiragolumab自此完全消失在罗氏管线中。从预期一路走高，到TIGIT几经失败，预期不断翻转再翻转，当初那批顶着质疑与压力的药企，终究没能等来好消息。这背后有一点不可忽视，当行业疯狂涌向一个热门靶点之际，科学理性容易被抛诸脑后。TIGIT至今未能成药，可能是其在肿瘤免疫调节中的作用从一开始就被高估，也可能是由于联合疗法的方案还有待优化。而在业内人士看来，针对TIGIT靶点的研发，在多个临床表现与预期之间产生了不小的差距，本质上，这体现了我们对该靶点的认知程度不足，先前基于这一靶点的一些预测可能是错误的。这也提醒我们，不要轻易对一个靶点的未来，极度乐观或悲观。不只是TIGIT，过往肿瘤学押注失败的历史不再少数，典型高投入失败案例IL-2、CD47等，成功者总是少数。 / 03 / 新的赌局轮回一个不争的事实是，创新药研发从来不是直线前进的旅程。虽然已有成功先例，但我们对免疫系统的认知依然有限，肿瘤免疫抑制微环境的复杂性和异质性，是阻碍免疫治疗前进的重要原因。加上创新药研发本就是一项成本高昂、风险高的业务。在药物最终上市之前，谁也无法预测最终的结果，即便是身经百战的大药企们。然而，如同TIGIT这样的惨痛教训也再次为我们带来启示。未来肿瘤免疫治疗，需要不断探索新的未知数，也需要更扎实的靶点与机制研究、更精准的患者分层又或是更创新的组合策略。与此同时，药企也需要在靶点验证严谨性与临床开发节奏间寻求一种平衡，避免上百亿学费重蹈覆辙。因为，资本可以在“靶点风口”间逐浪狂时，科学却需要匍匐于机制验证的荆棘之路。对整个行业来说，当旧靶点退场，新赌局早已开始。包括默沙东、GSK、罗氏等大药企先后放弃TIGIT的原因，还在于新的免疫治疗靶点和技术如双抗、ADC等不断涌现，尤其是PD-(L)1/VEGF双抗的崛起，让TIGIT的临床意义逐渐弱化。大药企也很难保证创新药的成功率，而它们更懂得战略性的撤退，为下一代突破性药物腾出资源与空间。以PD-(L)1/VEGF双抗为例，先驱康方生物已经让人看到了希望，并不断提高相关资产的价值。仅计算国产PD-(L)1/VEGF双抗的BD规模，首付款及收购款已经超过30亿美元，若达所有里程碑，总交易额将超150亿美元。如果算上BMS与BioNTech的百亿美元交易，总交易额已经接近300亿美元，更不要提还有正在观望的艾伯维等大药企，贡献新的交易额。在大药企的抢位与竞争下，已经有海外媒体发出了警示，一旦失败，PD-(L)1/VEGF双抗的灾难规模将令TIGIT风波相形见绌。面对新的科学博弈与研发对赌，所有入局者都需要在创新激情与科学严谨的钢丝上保持平衡。因为，真正的突破永远来自对未知的敬畏，而非对风口的贪婪。当然，每一次理性的撤退，也都是对下一次进击的蓄力。 PS：欢迎扫描下方二维码，添加氨基君微信号交流。

引进/卖出临床3期免疫疗法ASCO会议临床2期

2025-08-06

·BioPlus

Pfizer等6家MNC：2025 Q2管线调整，哪些项目被砍，哪些新增？

作者：Medicina 近期，MNC企业相继发布了其第二季度的财务报告，笔者据此对各企业的管线变动情况进行了整理。 01 Pfizer Programs Discontinued：1. PF-06425090, Prophylactic vaccine – protein subunit, Primary Clostridioides difficile (C. Difficile) Infection （艰难梭菌感染）2. Vepdegestrant (ARV-471) + VERZENIO® (abemaciclib), ER-targeting PROTAC® protein degrader + CDK4/6 inhibitor, ER+/HER2- 2L Metastatic Breast Cancer (VERITAC 4)3. Vedegestrant (ARV-471) + Atimocilib ER-targeting PROTAC® protein degrader + CDK4 inhibitor, ER+/HER2- 1L Metastatic Breast Cancer4. VELSIPITY™ (etrasimod), S1P inhibitor, Crohn's Disease5. PF-06954522, Glucagon-like peptide 1 receptor (GLP-1R) agonist, Chronic Weight Management6. PF-07293893, AMPKγ3 activator, Heart Failure7. PF-07820435, STING agonist, Advanced Solid Tumors8. felmetatug vedotin (PF-08046048) (B7H4V), B7H4-ADC, Advanced Solid Tumors 02 BMS Removed 1. Phase I：IL2-CD25 2. Phase II：afimetrotan（TLR7/8拮抗剂） New to Phase I 1. BMS-986500 in Solid Tumors (有人推测是CDK2 inhibitor?) 2. BMS-986517 in Solid Tumors 3. CD19 HD Allo CAR T in AID 4. RYZ401 in Solid Tumors 03 GSK Removed from Phase III 1. belrestotug (GSK4428859): Anti-TIGIT antibody, Non-small cell lung cancer 2. ibrexafungerp (GSK458448): Antifungal glucan synthase inhibitor, Invasive candidiasis Removed from Phase II 1. GSK3437949: Recombinant protein, adjuvanted, Malaria fractional dose 2. GSK3536852: GMMA, Shigella 3. sanfetrin cilexetil (GV118819): Serine beta lactamase inhibitor, Tuberculosis Removed from Phase I 1. GSK3536867: Bivalent conjugate, Salmonella (typhoid + paratyphoid A) New to Phase I GSK5458514: PSMAxCD3 T cell engaging bispecific antibody, Prostate Cancer 04 Sanofi Removed from Phase 2 1. amitelimab – HS (OX40L单抗，曾报道疗效不佳) 2. SAR444656 – AD/HS（SAR444656也称KT-474，为IRAK4降解剂；曾报道赛诺菲优先考虑临床前IRAK4降解剂KT-485，而不是推进KT-474，新候选药物KT-485在临床前显示出更高的选择性和活性，可能安全性更好） New in Phase 1 1. SAR448501 – inflammatory indication（原研Dren Bio，Dectin-1/CD20） 05 AZ Removed from Phase I 1. AZD5851: GPC3 CAR-T hepatocellular carcinoma (但AZD7003 China GPC3 CAR-T，hepatocellular carcinoma/squamous NSCLC，仍然在管线中，处于I期临床) 2. AZD6422: CLDN18.2 CAR-T solid tumors 3. NT-125: autologous, fully-individualised, multi-specific TCR-T targeting neoantigens solid tumors Removed from Phase II 1. Additional indication: zibotentan/dapagliflozin: endothelin A receptor （ETA）antagonist/SGLT2 inhibitor liver cirrhosis 2. Life cycle management: Ultomiris, anti-C5 mAb proliferative lupus nephritis New to Phase I 1. AZD0240: KRAS G12D armoured TCR-T solid tumours 2. AZD1613: inflammation and metabolism modulation kidney disease (anti-PAPPA单抗) 3. AZD4248: cellular health cardiorenal disease 4. AZD4360: CLDN18.2 ADC solid tumours (这是另一款新的CLDN18.2-ADC;此前从美雅珂/康诺亚获得的CLDN18.2 MMAE ADC AZD0901 现在处于临床III期) 5. AZD4954: Lp(a) inhibitor dyslipidaemia 6. Additional indication: AZD5492 CD20 TITAN T-cell engager systemic lupus erythematosus （CD20/CD8/TCR） 7. volrustomig avDLVF-RCC02: PD-1/CTLA4 bispecific mAb 1L advanced clear cell renal cell carcinoma (ccRCC) 06 Roche Removed from phase I （4 NMES）: 1. RG6279 eciskafusp alfa + T - solid tumors (RG6279为IL-2/PD1抗体融合蛋白) 2. RG6457 WRN covalent inhibitor - solid tumors 3. RG6414 USP1 inhibitor - solid tumors 4. RG7921 NME - RVO Removed from phase III： 1NME: 1. RG6058 tiragolumab + T - stage III unresectable 1L NSCLC （tiragolumab 为anti-TIGIT单抗） 2 AIs: 1. RG6058 tiragolumab + T + Avastin - 1L HCC （tiragolumab 为TIGIT单抗） 2. RG7601 Veneclexta + azacitidine - 1L MDS （Veneclexta为Bcl-2抑制剂） New to phase I (2 NMEs): 1. RG6505 PanRAS inhibitor - solid tumors（2025年3月，启动了I期临床，NCT06884618） 2. RG6327 NME - geographic atrophy （2025年5月，启动了I期临床NCT06961370） New to phase II（1 AI）： 1. RG6237 emugrobart (GYM 329) - obesity（2025年5月启动II期临床，NCT06965413，RG6237 +Tirzepatide vs. Tirzepatide ）欢迎大家加入BioPlus微信交流群，共同探讨。 BioPlus 微信交流群申请入群申请联系人：Lisa 邮箱：lisa.li@bp-bioplus.com 电话：18662346610（同微信）入群申请，请先添加Lisa微信，并分享名片入群画像：Biotech/药厂研发/BD、投资机构、临床医生等入群福利：不定时行业资料包分享拓展阅读 BioPlus-海外寻找资产系列： 1.AACR复盘：9家CDH17-ADC数据对比 2.自免小众靶点APRIL，正在悄悄火起来了！ 3. STEAP1，会成为ADC与TCE的下一个爆款靶点么？ BioPlus国际大会跟踪系列： 1. 2025 ASCO：ADC、双抗/多抗，有哪些看点？（附一览表） 2. 2025 AACR 双抗与ADC有哪些看点？ 3. 小细胞肺癌领域，下一步将如何“破局”，ADC or TCE？ 4. ELCC 讨论：NSCLC的ADCs最新进展 5. 未来ADC发展方向：新靶点，新载荷，双靶点/双表位... 6. 2025 ASCO 重点项目临床数据：有哪些精彩看点？ 7. 2025 ASCO 重点项目临床数据 BioPlus靶点/管线研究系列： 1. “待爆”：CDH17 ADC项目大比拼，谁将脱颖而出? 2. PD-1激动剂在自免疾病项目数据盘点：失败项目的“坑”与启示 3. 上临床就能卖？DLL3 ADC这么好卖？ 4. 胰腺癌三大热门靶点：CLDN18.2、EGFR、RAS 5. TSLP/SCF双抗，下一个自免待爆靶点组合？ 6. GPC3靶点临床屡败，TCE能改写格局么？ 7. 亮相AACR，曾被临床终止的ADC靶点Ly6E，能否卷土重来？ 8. 最高18.45亿美元！赛诺菲为何重金买了两款TL1A双抗？ 9. 2025 Q1：BMS、Sanofi和Roche管线调整，哪些项目被砍？ 10. 现场！2025AACR：KRAS抑制剂的百花齐放 11. IL-17小分子抑制剂，能否杀出重围？ 12.全球首款：华东医药申报MUC17 ADC药物 13.荨麻疹 first-in-class双抗提交临床试验申请 BioPlus技术平台深入剖析系列： 1. TCE 免疫共刺激信号之选：CD2，一颗冉冉升起的新星 2. BD爆发前夜！6家TCE Probody技术平台深度盘点 3. TCE Probody：Amgen携重磅技术“破局“，改写行业格局？ 4. 有人放弃，有人前行！自免TCE全球管线大盘点 5. Immunocore将TCR疗法照进现实，向自免疾病迈进 6. B细胞清除免疫重置：SLE等疾病长效缓解终成现实！ 7. 国内50家CD3平台序列来源汇总 8. CD28共刺激最终章？ZW209 DLL3/CD3/CD28 三抗剑指 Amgen 9. TCE 结构之争落幕：行业用行动给出 “标准答案” 10. CD3 VHH猴交叉：重要吗？ 11.Genentech创新前沿：口服VHH抗体，靶向IL-23R 12.AbbVie专利公开：靶向PSMA/STEAP1 双抗ADC BioPlus人物专访： 1. 专访肖亮：卖青苗不一定是坏事，这是中国Biotech长成参天大树的必经之路 2. 专访王刚，恺佧生物这些年的“出海”之旅？

免疫疗法临床1期细胞疗法抗体药物偶联物疫苗

2025-08-04

·思齐俱乐部

罗氏、GSK等大批药企相继撤离该赛道……

来源：制药网图片：花瓣网近日，TIGIT 靶点凭独特的免疫调节机制，曾被业界认为将是改写肿瘤治疗格局的 “黄金靶点”，并引得罗氏、GSK、BMS、诺华、百济神州等众多国内外药企纷纷重金投入。然而，当下大批重磅玩家却正在加速撤退离场。罗氏日前发布了2025年半年报，同时宣布砍掉7大研发管线。其中，其全球头个进入III期的TIGIT抑制剂——RG6058(tiragolumab)仅剩的两项III期临床，也已经正式终止。这意味着，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。据悉，TIGIT靶点的价值是罗氏在2009年发现的，2021年其曾经围绕着Tiragolumab开展了有数10项II/III期临床试验。但从2022年起，罗氏在TIGIT 研发上就开始接连失败。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，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。今年Q1，罗氏还进一步终止了其联合Tecentriq治疗局部晚期食管癌的III期研究。 5月，GSK宣布停止开发收购而来的TIGIT抗体药物——belrestotug，该决定是基于 GALAXIES Lung-201 和 GALAXIES H&N-202 两期临床研究的最新中期分析结果，这些研究未达到继续开发的既定疗效标准。基于两项研究结果，该合作以及所有包含 Belrestotug 的研究队列都将终止，包括正在进行的 GALAXIES Lung-301 III 期试验的新入组。 4月，百济神州宣布终止 TIGIT抗体欧司珀利单抗(Ociperlimab)的肺癌适应症临床开发，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。据悉，在此之前，百济神州就已停止了欧司珀利单抗另外一项在不可手术III期PD-L1表达≥1%的NSCLC III期试验。截至2024年12月，该项目已入组2000多例患者，累计投入达20.90亿元。这一巨额投入的终止，标志着百济神州在TIGIT靶点研发上的重大挫折。 2024年8月，Agenus公司宣布收到百时美施贵宝(BMS)的通知，后者由于管线开发战略调整，决定归还与其共同开发的TIGIT/CD96双特异性抗体BMS-986442 (AGEN1777)的权益，并自愿终止双方之前签订的许可协议。该决定自 2025 年 1 月 26 日起生效。 2024年12月，默沙东发布公告，经评估后，决定停止两个项目的开发，其中之一为TIGIT单抗vibostolimab。据了解，在8月份，默沙东就终止了K药+TIGIT用于一线治疗小细胞肺癌的三期临床。此外，在5月份，因为免疫副作用，默沙东还停止了K药+TIGIT联用辅助治疗黑色素瘤的三期临床。业内分析认为，2025 年 TIGIT 赛道的退潮并非终点，而是行业从 “靶点狂热” 转向 “科学驱动” 的转折点。失败的教训虽沉重，但同时也将促使科学界更精准地探索疾病机制。未来，药企需在靶点选择、临床试验设计和资源分配上进行系统性革新，同时通过技术创新(如双抗、Fc 改造)和跨领域协同，为免疫治疗开辟新路径。点击阅读原文了解更多

临床3期临床失败并购临床成功临床终止

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

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
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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临床结果

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


NCT04958811 (WCLC2025)	临床2期	鳞状细胞肺癌二线 PDL1 TPS ≥1%	12	bevacizumab+Atezolizumab+Tiragolumab	範鹹襯齋醖襯壓膚餘鹹(鏇選醖衊簾蓋遞遞衊齋) = 衊醖鑰鑰鬱艱遞餘襯淵餘襯窪窪蓋繭夢壓積鹽 (糧蓋製膚願獵淵憲遞夢 ) 更多	积极	2025-09-07
NCT04832854 (SKYSCRAPER05, WCLC2025)	临床2期	非小细胞肺癌新辅助 \| 辅助 PDL1 expression ≥ 50%	50	Atezolizumab+Tiragolumab (Cohort A (PD-L1 ≥50%))	膚蓋鹽構觸醖鹽夢構簾(餘窪廠願蓋壓鹹齋選蓋) = 鬱壓蓋範顧醖願獵積築膚廠鹽衊遞築膚繭餘醖 (願醖選範鏇築觸壓艱選, 30.3 ~ 94.9) 更多	积极	2025-09-07
				Atezolizumab+Tiragolumab+Platinum containing dual drug chemotherapy (Cohort B (PD-L1 any))	膚蓋鹽構觸醖鹽夢構簾(餘窪廠願蓋壓鹹齋選蓋) = 鬱淵網糧遞繭鏇遞鹽齋膚廠鹽衊遞築膚繭餘醖 (願醖選範鏇築觸壓艱選, 35 ~ 67) 更多
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	襯鏇簾選鏇糧淵艱範夢(繭製遞襯夢製鬱繭齋淵) = 鹹簾網簾遞餘鬱網齋構廠艱窪淵糧齋蓋鏇鬱鏇 (繭廠鑰繭襯網構築範鹽, 5.6 ~ 9.8) 更多	不佳	2025-04-28
				Placebo + Atezolizumab 1200 mg IVAtezolizumab 1200 mg IV	襯鏇簾選鏇糧淵艱範夢(繭製遞襯夢製鬱繭齋淵) = 窪餘襯蓋觸襯壓壓築繭廠艱窪淵糧齋蓋鏇鬱鏇 (繭廠鑰繭襯網構築範鹽, 4.4 ~ 7.0) 更多
NCT04300647 (SKYSCRAPER-04, CTgov)	临床2期	PD-L1阳性宫颈癌	172	Atezolizumab (Atezolizumab)	鑰積醖艱鹽構選網築鬱 = 廠憲簾選壓製窪鬱製醖憲醖鑰艱顧鹹顧製鹹壓 (鑰齋膚憲築觸襯製鏇鏇, 鑰襯獵繭遞積窪齋壓窪 ~ 憲製淵構製簾齋衊糧獵) 更多	-	2025-02-07
				Atezolizumab+Tiragolumab (Tiragolumab Plus Atezolizumab)	鑰積醖艱鹽構選網築鬱 = 壓壓餘願選淵艱廠壓鬱憲醖鑰艱顧鹹顧製鹹壓 (鑰齋膚憲築觸襯製鏇鏇, 顧鹽網淵糧遞廠鬱鹹鏇 ~ 糧淵顧鬱襯構築鹹鏇鬱) 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	淵膚壓膚糧簾衊範壓顧(積觸顧構構蓋觸醖鑰鑰) = 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. 糧廠廠繭鏇鏇蓋廠網蓋 (願餘壓膚襯遞鏇鏇衊壓 ) 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	製選糧獵鏇鏇簾選淵顧(網繭襯鑰範廠選糧醖鑰) = 範遞蓋壓壓顧鏇衊醖遞鏇選鏇廠觸鬱鬱鏇觸願 (積築範製夢鑰餘夢願範, 15.2 ~ 23.8) 更多	不佳	2024-12-12
				Placebo + Pembrolizumab 200 mg IV + Carboplatin/Cisplatin + Pemetrexed IV	製選糧獵鏇鏇簾選淵顧(網繭襯鑰範廠選糧醖鑰) = 鹹範鬱簾艱製鬱齋積餘鏇選鏇廠觸鬱鬱鏇觸願 (積築範製夢鑰餘夢願範, 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	願簾選艱憲憲積膚艱齋(膚齋鑰顧選壓顧網繭範) = did not reach the primary endpoint. 製鬱築淵壓窪鑰醖鬱糧 (齋夢窪鑰廠範夢餘淵艱 ) 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	獵襯觸夢廠鹹齋衊鏇夢 = 蓋鹹獵構壓壓網獵選夢蓋蓋憲構艱憲齋觸鏇遞 (蓋衊鑰壓遞壓鹽獵齋廠, 鹽遞衊衊壓鏇衊廠鬱遞 ~ 膚衊獵鹹廠鬱蓋積選憲) 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	願糧窪製憲壓鑰蓋醖遞(醖糧膚鹽夢鑰觸製遞觸): 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)	鏇襯廠網觸憲網顧鹹餘(選膚願窪網夢鹹觸鑰遞) = 醖鏇壓觸壓齋顧網餘廠鏇積鏇鬱鹹築願簾壓繭 (窪餘憲憲衊淵襯鹹範鹹 )	积极	2024-03-22