A Phase II Study of N-803 Alone or in Combination With BN-Brachyury Vaccine or Bintrafusp Alfa (M7824) for Participants With Castration Resistant Prostate Cancer

Background:
Prostate cancer does not trigger a strong immune response in the body. Hormone therapy, to reduce levels of testosterone in the body, can be helpful to treat some prostate cancers. However, castration-resistant prostate cancer (CRPC) keeps growing even when the testosterone is reduced to a very low level. Men with metastatic CRPC survive an average of only 3 years. More effective treatments are needed.
Objective:
To test whether an immunotherapy drug (N-803), alone or in combination with other drugs, can help treat CRPC.
Eligibility:
Males aged 18 or older with CRPC. Prior treatment with testosterone-lowering therapy is required.
Design:
Participants will be screened. They will have blood and urine tests. They will have a CT scan of the chest, abdomen, and pelvis.
They will continue to receive hormone therapy for prostate cancer.
Participants will come to the NIH clinic once a week for the first 4 weeks. Then they will come once every 2 weeks. Visits will last up to 8 hours. The study will continue up to 3 years.
All participants will receive N-803 once every 2 weeks. The drug is injected just under the skin with a small needle.
Some participants will receive N-803 plus another drug (brachyury vaccine). This drug is also injected under the skin with a small needle.
Some participants will receive N-803 plus a different drug (bintrafusp alfa) once every 2 weeks. This drug is given through a tube attached to a needle placed in a vein in the arm.
Some participants may receive all 3 drugs.
Participants will have imaging scans every 12 weeks.

开始日期2024-04-01

申办/合作机构

National Cancer Institute

NCT05012098

/ Completed临床2期IIT

Phase 2 Study of Bintrafusp Alfa in Recurrent/Metastatic Olfactory Neuroblastoma (BARON).

Background:
Olfactory neuroblastoma (ONB) is a rare cancer of the nasal cavity. At diagnosis, it is usually locally advanced. It tends to spread to the neck. Sometimes it spreads to the lungs and bones. Researchers want to find a better way to treat it.
Objective:
To learn if giving immunotherapy drug bintrafusp alfa can help ONB shrink or disappear.
Eligibility:
People aged 18 years and older diagnosed with recurrent or metastatic ONB that has not responded to standard treatment.
Design:
Participants will be screened with a medical history, blood and urine tests, and physical exam. Their ability to perform their normal activities will be assessed. They will have an electrocardiogram to evaluate their heart. They will have imaging scans and/or a nuclear bone scan, as needed. For some scans, they may receive a contrast dye.
Some screening tests will be repeated during the study.
Participants will receive bintrafusp alfa once every 2 weeks for 26 doses. They will get it intravenously over 60 minutes. They may get other medicines to prevent side effects. They will complete health questionnaires. Visits will last 4-6 hours.
Participants may have optional tumor biopsies.
Participants will have an end of treatment visit within 7 days after they stop taking the study drug. About 28 days after treatment ends, they will have a safety visit. They will have follow-up visits every 3 months for the first year, then every 6 months for years 2-5, and then once a year after that for the rest of their life. If their disease progresses, they may be eligible for re-treatment with the study drug

开始日期2022-06-21

申办/合作机构

National Cancer Institute

NCT04874311

/ Recruiting临床2期IIT

Bintrafusp Alfa and Doxorubicin Hydrochloride in Treating Patients With Advanced Sarcoma. TRUST Study

This study encompasses two multicenter, prospective, open-labeled, 2-arm, non-comparative randomized phase II trials to assess the antitumor activity of bintrafusp alfa in association with doxorubicin

开始日期2022-03-01

申办/合作机构

Institut Bergonié

[+1]

100 项与必特芙普α 相关的临床结果

登录后查看更多信息

100 项与必特芙普α 相关的转化医学

登录后查看更多信息

100 项与必特芙普α 相关的专利（医药）

登录后查看更多信息

项与必特芙普α 相关的文献（医药）

2026-02-05·ONCOLOGIST

The quadruple immunotherapy for colorectal cancer (QuICC) trial for mismatch repair-proficient metastatic colorectal cancer

Article

作者: Turkbey, Evrim B ; Pastor, Danielle M ; Tschernia, Nicholas P ; Cordes, Lisa ; Marté, Jennifer L ; Karzai, Fatima ; Floudas, Charalampos S ; Redman, Jason M ; Hodge, James W ; Gulley, James L ; Brownell, Isaac ; Maeng, Hoyoung M ; Donahue, Renee N ; Soon-Shiong, Patrick ; Schlom, Jeffrey ; Strauss, Julius ; Bracken-Clarke, Dara

Abstract:

Background:

Despite successes in other malignancies, immune checkpoint blockade (ICB) has not demonstrated reproducible efficacy in mismatch repair-proficient (pMMR) colorectal cancer (CRC). Preclinical studies indicate that multitargeted combination immunotherapy may sensitize resistant tumors to immune-mediated killing. This trial was designed to test this hypothesis by combining agents to induce and augment an immune response in pMMR CRC.

Methods:

In this single-center, phase 1/2 trial, eligible patients had pMMR, RECIST v1.1-measurable metastatic CRC, ≥2 prior lines of therapy, and no prior immunotherapy. The primary endpoint was objective response rate. Patients received triplet therapy: CV-301 (CEA/MUC-1 vaccine), N-803 (IL-15 receptor superagonist), bintrafusp alfa (bifunctional anti-PD-L1/TGFβ “trap”), or quadruplet therapy (adding PDS01ADC [tumor-targeted IL-12 immunocytokine]).

Results:

Between September 2020 and September 2022, 32 patients enrolled in triplet (n = 12) and quadruplet (n = 20) therapy. The combinations had toxicity profiles consistent with each individual agent included. One complete response durable for 29+ months occurred in a patient with RAS wild-type CRC metastatic to lymph nodes who received quadruplet therapy.

Conclusion:

Quadruplet therapy produced one objective response in unselected mCRC patients (n = 20). There were no responses with triplet therapy (n = 12). The role of ICB-based combination immunotherapy in pMMR CRC remains unclear. NCT04491955

2026-02-01·MOLECULAR IMAGING AND BIOLOGY

A Bioimaging Study of 89Zr-Bintrafusp Alfa PET Scans in Patients with Advanced or Metastatic NSCLC Receiving Bintrafusp Alfa Alone or in Combination with Chemotherapy

Article

作者: Gan, Hui K ; O'Keefe, Graeme J ; Scott, Andrew M ; Mathai, Jared ; Scott, Fiona E ; Palmer, Jodie ; Parakh, Sagun ; McDonald, Alexander F ; Lee, Sze Ting ; Smith, Vivian ; Wichmann, Christian W ; Guo, Nancy

RATIONALE:

Bintrafusp alfa is a first-in-class bifunctional fusion protein composed of the extracellular domain of the human transforming growth factor β receptor II (TGF-βRII or TGF-β "trap") and human immunoglobulin 1 antibody which blocks programmed cell death ligand 1 (PD-L1). This trial aimed to investigate the biodistribution of ⁸⁹Zr-bintrafusp alfa in patients with NSCLC with PD-L1 expressing tumors.

METHODS:

Five lung cancer patients were recruited with PD-L1 staining more than 1% of tumor cells. Patients underwent ⁸⁹Zr-bintrafusp alfa intravenous infusion (100 mg IV) on Day 1 followed by sequential PET imaging to determine the biodistribution of ⁸⁹Zr-bintrafusp alfa. Patients then received treatment with bintrafusp alfa (1200 mg IV) on day 15 and 29, with the latter including further ⁸⁹Zr-bintrafusp alfa to determine the effects of bintrafusp alfa treatment on receptor occupancy. Patients continued with bintrafusp alfa monotherapy, or in combination with chemotherapy for those without objective response to monotherapy, until disease progression or unacceptable toxicity. The study stopped after five patients due to the overall cessation of the bintrafusp alfa program.

RESULTS:

⁸⁹Zr-bintrafusp alfa imaging was feasible and well tolerated. All patients showed tumor specific uptake without normal tissue uptake. There was no correlation between uptake and tissue PD-L1 expression or outcomes, likely due to sample size. Inter- and intra-patient heterogeneity was observed and optimal treatment regimens will need to address this in future.

CONCLUSIONS:

⁸⁹Zr-bintrafusp alfa imaging is safe, feasible and provides relevant tumor targeting information for patient selection and treatment.

2026-02-01·Journal for ImmunoTherapy of Cancer

Potent antitumor activity through dual targeting of PD-L1 and TGF-β pathways in the glioma tumor microenvironment

Article

作者: Nuñez, Nicolas Gonzalo ; Kienzler, Jenny C ; Roth, Patrick ; Becher, Burkhard ; Mastall, Maximilian ; Weller, Michael ; Silginer, Manuela ; Weiss, Tobias

Background:

Glioblastoma, one of the most aggressive brain tumors, has been largely resistant to conventional immunotherapies, underscoring the need for novel treatment approaches. A promising strategy involves simultaneously inhibiting immunosuppressive pathways in the tumor microenvironment, as these pathways play pivotal roles in immune evasion. However, the therapeutic potential of combined targeting of these key immunosuppressive pathways in glioblastoma remains underexplored. We hypothesized that co-targeting the transforming growth factor (TGF)-β and PD-1 pathways could enhance immune responses against glioblastoma.

Methods:

Human glioblastoma datasets were interrogated for the expression of PD-L1, TGF-β, and TGF-β target genes. Bintrafusp alfa, a first-in-class bifunctional fusion protein that blocks PD-L1 while sequestering TGF-β in the tumor microenvironment, was used to simultaneously inhibit both pathways. Its effects were assessed in vitro using human and mouse glioma cells and in vivo in immunocompetent, syngeneic mouse glioma models. High-dimensional flow cytometry was used to analyze treatment-induced changes in the tumor microenvironment.

Results:

We observed a strong correlation between TGF-β and PD-L1 co-regulation, suggesting interconnected immunosuppressive mechanisms as part of a gene expression network. In vitro, bintrafusp alfa inhibited TGF-β-induced Smad2 phosphorylation, a bona fide response marker of TGF-β pathway activation, and enhanced immune cell-mediated killing of glioma cells. In vivo, combined targeting of both immunosuppressive pathways significantly improved survival of glioma-bearing mice, with long-term survivors exhibiting protection from tumor re-challenge. This survival benefit was not seen in T cell-deficient mice, confirming the necessity of adaptive immunity. High-dimensional flow cytometry of single-cell suspensions from tumor-bearing hemispheres revealed a distinct remodeling of immune subsets in the bintrafusp alfa-treated group compared with control-treated mice.

Conclusions:

Our findings provide strong support for the combined targeting of TGF-β and PD-L1 as a promising immunotherapeutic strategy to overcome immunosuppressive barriers in glioblastoma and induce potent antitumor responses.

142

项与必特芙普α 相关的新闻（医药）

2026-06-18

·研日新

研日新日报 ·4| 06月18日皮肤科 | 消化内科 | 精神科

日报精选医学文献今日精选20篇医学文献，查看更多请点击阅读原文本文支持继续浏览摘要内容；完整摘要、收藏文章、订阅管理等完整功能，请前往小程序「医研日新」。前往小程序查看更多与订阅收藏 1. Single-cell multi-omics dissection of RevitalAge Markers uncovers age-dependent immunotherapy resistance and druggable targets in melanoma. [Melanoma] Biology direct | 2026-06-17 | IF 5.7 AIST3GAL4可作为老年黑色素瘤患者免疫治疗耐药的预测标志物和潜在治疗靶点，联合RAF/MEK抑制剂具有应用前景。摘要Aging-related molecular reprogramming profoundly influences melanoma progression and therapeutic sensitivity, yet underlying mechanisms remain poorly understood. We constructed a comprehensive multi-omics atlas integrating mutations, transcription, methylation, and copy number variations, utilizing the MOFA algorithm to uncover key age-driving factors. Among 20 factors, Factor6 exhibited significa...查看完整摘要 2. Breaking the mast cell-T helper 2 axis in atopic dermatitis: Insights from oral MRGPRX2 antagonist. [Dermatitis] The Journal of investigative dermatology | 2026-06-17 | IF 5.7 AIMRGPRX2拮抗剂通过双重机制（抑制肥大细胞活化+阻断Th2轴）为难治性特应性皮炎提供精准靶向治疗新选择。 3. Bintrafusp alfa for patients with recurrent or metastatic olfactory neuroblastoma. [Skin Diseases] Cancer immunology, immunotherapy : CII | 2026-06-17 | IF 5.1 AIBintrafusp alfa在R/M ONB中虽未达客观缓解终点，但展现可控安全性及部分患者的持久获益，证实了该罕见肿瘤免疫治疗临床试验的可行性。摘要There is no established treatment for patients with recurrent/metastatic (R/M) olfactory neuroblastoma (ONB), a rare sinonasal tumor. We conducted the first immunotherapy clinical trial (NCT05012098) in patients with R/M ONB, to evaluate the activity of the bifunctional TGF-β "trap"/anti-PD-L1 fusion protein bintrafusp alfa (BA). Patients received BA (1200 mg, intravenously) every 2 weeks. Primary...查看完整摘要 4. Programmable mRNA 3'UTR engineering restores MHC-I and overcomes immune evasion in prostate cancer. [Melanoma] Nature biomedical engineering | 2026-06-16 | IF 26.8 AI该研究为克服前列腺癌免疫治疗耐药提供了新靶点，通过LNP递送的3'UTRCES平台精准恢复MHC-I表达，有望将免疫冷肿瘤转化为热肿瘤，提升ICT疗效。摘要Immune-cold tumours such as prostate cancer often resist immune checkpoint therapies (ICT) due to impaired antigen presentation via major histocompatibility complex class I (MHC-I). While MHC-I downregulation is a common immune evasion mechanism, no approved therapies selectively restore MHC-I expression in tumours. We developed a programmable RNA engineering platform, termed the 3'UTR CRISPR/dCas...查看完整摘要 5. Clinical utility of immune biomarker staining of skin biopsies in psoriasis and eczematous dermatitis: A single-center retrospective analysis. [Psoriasis] Journal of the American Academy of Dermatology | 2026-06-16 | IF 12.8 AI免疫生物标志物染色可作为银屑病与湿疹性皮炎鉴别诊断的有效辅助工具，尤其对组织形态学重叠的疑难病例具有重要的临床参考价值。 6. AKAP1 enhances glycogen accumulation and hepatocarcinogenesis through YTHDF2-mediated G6PC mRNA decay. [Carcinoma, Hepatocellular] Signal transduction and targeted therapy | 2026-06-16 | IF 40.8 AIAP-21肽抑制剂通过靶向AKAP1线粒体定位可有效抑制糖原积累和肝癌发生，为HCC提供了一种新颖且无明显毒性的治疗策略。摘要During recent years, a growing body of evidence has revealed that metabolic rewiring of glycogen is a hallmark of cancer that plays a significant role in tumor development and progression. Nonetheless, the molecular mechanism underlying the dysregulation of glycogen remains largely unknown. In this study, using liver-specific AKAP1 depletion and overexpression mouse models, we demonstrated that AK...查看完整摘要 7. Valorization of Sea Buckthorn (Hippophae rhamnocaides L.) Leaves: Polyphenol-Rich Extract Targeting Helicobacter pylori Virulence and Gastric Mucosal Homeostasis. [Helicobacter Infections] Journal of agricultural and food chemistry | 2026-06-05 | IF 5.7 AI沙棘叶提取物对多重耐药幽门螺杆菌具有显著抑制作用，并兼具黏膜保护功效，可作为传统抗生素疗法外的一种天然辅助治疗选择。摘要Sea buckthorn (Hippophae rhamnoides L.) leaves are rich in polyphenols and exhibit potent activity against Helicobacter pylori. This study found that its extract demonstrates a dual mechanism of action, inhibiting bacterial virulence while protecting the gastric mucosa. For multidrug-resistant strains, the minimum inhibitory concentration (MIC) range of this extract was 0.08-0.64 mg/...查看完整摘要 8. Patient-derived organoids from metastatic colorectal cancer mirror tumor heterogeneity and predict patient survival and drug sensitivity. [Liver Neoplasms] Cell reports. Medicine | 2026-05-28 | IF 11.7 AI类器官形态学特征可快速预测转移性结直肠癌药物敏感性，囊性形态提示更高化疗敏感性，为个性化治疗决策提供实时体外药敏参考。摘要This study reports the pharmacogenomic analysis of tumor heterogeneity in a living biobank of 213 organoids derived from liver metastases of 102 patients with metastatic colorectal cancer. Successful organoid establishment reflects poorer chemosensitivity and patient survival. Molecular fidelity is confirmed in tumor-organoid pairs, and multi-modal phenotypes are defined based on organoid morpholo...查看完整摘要 9. Leveraging longitudinal data to boost statistical power for gene-environment interaction analysis. [Mental Disorders] Nature computational science | 2026-06-16 | IF 12.0 AISAGELD方法通过高效利用纵向随访数据显著提升基因-环境交互分析的统计效能，可帮助临床识别更多疾病风险基因位点，为个体化预防策略提供遗传学依据。摘要Gene-environment interaction (G×E) analyses play a crucial role in advancing genetic discovery, addressing missing heritability, and facilitating precision medicine. However, existing G×E methods are mostly designed for cross-sectional data, limiting the utility of longitudinal data. Here we propose SAGELD, a scalable and accurate genome-wide G×E method for longitudinal traits that controls for sa...查看完整摘要 10. Digital Tools to Support Mental Health in Later Life: Scoping Review of Systematic Reviews. [Mental Disorders] 综述 | Current psychiatry reports | 2026-06-16 | IF 6.7 AI数字工具在改善老年人抑郁症状方面具有一定潜力，但当前证据质量参差不齐，临床应用时需关注工具的可用性评估及长期有效性验证。摘要This scoping review synthesises existing evidence from systematic reviews on the effectiveness and implementation of digital mental health interventions among community-dwelling older adults. Twenty-one systematic reviews were included. Results showed that a range of digital tools demonstrate potential to improve common mental health and psychosocial symptoms among older adults, with most evidence...查看完整摘要 11. The Joy and the Pain of Being Alone: Managing the Solitude-Loneliness (SOLO) Paradox in People High on the Autism Spectrum. [Autism Spectrum Disorder] 综述 | Clinical child and family psychology review | 2026-06-16 | IF 6.1 AI自闭症患者的孤独感与独处偏好可同时存在且相互矛盾，临床干预需平衡其社交需求与独处偏好，而非简单鼓励社交接触。摘要This narrative review examines the complex relationship between autism and two fundamental social needs: the need to belong and the need to be alone, which underpin the conceptually distinct experiences of loneliness and solitude. After outlining core features of autism spectrum disorder-focusing on characteristic patterns of social functioning across the spectrum-we synthesize evidence showing th...查看完整摘要 12. Distinct contributions of schizophrenia and neurotransmitter pathway genetic liability to neurocognition and antipsychotic efficacy in drug-naïve first-episode schizophrenia. [Schizophrenia] Molecular psychiatry | 2026-06-15 | IF 9.6 AIGABA和5-HT通路多基因风险评分可预测抗精神病药疗效，有望成为指导个体化用药的潜在生物标志物。摘要The genetic mechanisms underlying heterogeneity in symptom presentation and antipsychotic response in schizophrenia remain unclear, limiting the development of personalized treatment. We integrated genome-wide schizophrenia polygenic risk scores (SZ-PRS) and pathway-specific PRSs (pPRSs) for four major neurotransmitter systems to examine their associations with clinical phenotypes across the cours...查看完整摘要 13. A novel composite model of PTSD induced by social bullying: validation via multidimensional behavioral and molecular biomarkers. [Mental Disorders] Molecular psychiatry | 2026-06-15 | IF 9.6 AI新型社会欺凌模型填补了社会创伤相关PTSD动物模型的空白，社交回避表型可指导临床识别高危个体，氟西汀的疗效验证为此类患者提供治疗参考。摘要Post-traumatic stress disorder (PTSD) is a debilitating psychiatric condition characterized by persistent fear memory, hyperarousal, and social impairment. Mounting evidence highlights the critical role of social stress, such as bullying, in triggering PTSD. However, progress in elucidating the underlying mechanisms and developing effective treatments has been hindered by the lack of animal models...查看完整摘要 14. Alterations in Cardiac and Systemic Metabolism in Heart Failure. [Heart Failure] 综述 | Circulation. Heart failure | 2026-06-17 | IF 7.8 AIHFrEF与HFpEF存在截然不同的代谢异常模式，针对代谢通路的新疗法（SGLT-2i、GLP-1RA）可能通过纠正代谢紊乱改善患者预后。摘要Altered cardiac and systemic metabolism is a hallmark of heart failure (HF). In the failing heart, cardiomyocytes develop alterations in substrate preference, mitochondrial oxidative metabolism, and the shuttling of high-energy phosphates from mitochondria to the cytosol that compromise energetic efficiency and contribute to disease progression. At the systemic level, neurohormonal activation play...查看完整摘要 15. The microbiome in reptile health, disease, and ecology. [Zoonoses] 综述 | Microbiology and molecular biology reviews : MMBR | 2026-06-17 | IF 7.8 AI爬行动物微生物组研究揭示了外热性动物独特的宿主-微生物互作模式，为理解脊椎动物微生物组多样性及珍稀物种保护提供重要参考。摘要SUMMARYReptiles are a diverse and speciose class of animals that are broadly threatened by habitat loss, climate change, and other factors. From a microbiological perspective, reptiles have historically been examined as a source of disease, particularly salmonellosis, with most studies being culture-based investigations into causative agents of disease and potential for zoonoses. More recent work ...查看完整摘要 16. Application of hydrogel technologies in the treatment of musculoskeletal disorders. [Osteoarthritis] Chinese medical journal | 2026-06-17 | IF 7.5 AI水凝胶技术为骨关节炎、软骨损伤等常见MSDs提供了有前景的非手术再生治疗策略，但临床转化仍需解决机械耐久性、生物活性可控释放及规模化生产等关键挑战。摘要Musculoskeletal disorders (MSDs) represent a diverse group of conditions affecting bones, cartilage, intervertebral discs, tendons, muscles, and related structures, and continue to be a leading cause of global disability. Despite advancements in surgery and pharmacotherapy, issues such as incomplete regeneration, limited longevity, and procedure-related complications remain unresolved. As a result...查看完整摘要 17. Tenecteplase Beyond the 4.5-h Window for Patients with Acute Ischemic Stroke: An Updated Meta-Analysis of Randomized Controlled Trials. [Hemorrhage] 系统综述 | CNS drugs | 2026-06-17 | IF 7.4 AI对于发病超过4.5小时的急性缺血性卒中患者，替奈普酶可显著改善功能预后，虽症状性颅内出血风险略增，但绝对值低，可作为经筛选患者的有效溶栓选择。摘要Intravenous thrombolysis (IVT) is the established treatment for acute ischemic stroke (AIS) when administered within 4.5 h of the last known well (LKW) status. However, this narrow therapeutic window limits the number of patients eligible for treatment. In this context, tenecteplase (TNK) is being investigated as an alternative thrombolytic agent in the extended time window. The objective of this ...查看完整摘要 18. An injectable SFMA/HA-E hydrogel for sustained delivery of hucMSC-derived exosomes promotes myocardial repair after infarction. [Heart Failure] Stem cell research & therapy | 2026-06-17 | IF 7.1 AI可注射水凝胶缓释人脐带间充质干细胞外泌体可实现单次给药显著改善心功能，为心肌梗死患者提供一种微创、高效的细胞衍生生物疗法新选择。摘要Myocardial infarction (MI) causes permanent loss of cardiomyocytes and heart failure. Human umbilical cord mesenchymal stem cell-derived exosomes (hucMSCs-Exos) have shown therapeutic potential. Still, their clinical utility is limited by rapid systemic clearance, highlighting the need for a delivery system to achieve sustained release and effect. We fabricated an injectable, photopolymerizable hy...查看完整摘要 19. Long-term metabolically unhealthy aging, its underlying molecular underpinnings, and association with cognitive impairment: a 12.4-year longitudinal cohort study. [Hypertension] BMC medicine | 2026-06-17 | IF 7.0 AI代谢不健康衰老与认知功能下降和脑结构萎缩密切相关，通过监测代谢指标和特定生物标志物可早期识别高危人群，为延缓认知衰退提供干预窗口。摘要Individuals experience heterogeneous aging processes closely associated with metabolism. However, it remains unclear whether older adults undergo different metabolic health-related aging patterns over time. We aimed to investigate the long-term metabolic health-related aging trajectories, their associations with cognitive function, and underlying molecular underpinnings among older adults. This st...查看完整摘要 20. Retinal Vascular Caliber: 6 to 12 Months and 15 to 25 Years Following Hypertensive Pregnancy. [Hypertension] Hypertension (Dallas, Tex. : 1979) | 2026-06-17 | IF 6.9 AI子痫前期女性产后存在持续的视网膜血管异常，这一发现提示临床医生应对此类患者进行长期心血管风险监测。摘要Women display retinal vessel caliber abnormalities after hypertensive pregnancy, but whether these predate or reflect vascular aging is unknown. Retinal imaging was performed in 2 cohorts: 196 women at 6 to 12 months postpartum (167 hypertensive, 29 normotensive), and 105 women at 15 to 25 years postpartum (64 hypertensive, 41 normotensive), using identical imaging/analysis protocols (Imedos Healt...查看完整摘要在小程序获取完整功能收藏文章、管理订阅、查看本期完整摘要与个性化内容，请前往小程序「医研日新」。前往小程序查看更多内容免责声明：仅供学术交流参考，不构成任何医学建议或诊疗指导

2026-06-18

·生物通

用于复发性或转移性嗅神经母细胞瘤患者的Bintrafusp alfa

摘要背景对于患有复发性/转移性嗅神经母细胞瘤（ONB）的患者，目前尚无标准治疗方案，这是一种罕见的鼻窦肿瘤。我们开展了首项针对R/M ONB患者的免疫疗法临床试验（NCT05012098），旨在评估双功能TGF-β“陷阱”/抗PD-L1融合蛋白bintrafusp alfa（BA）的疗效。方法患者每两周接受一次BA治疗（1200毫克，静脉注射）。主要评估指标为总体缓解率（ORR）；次要评估指标包括安全性、无进展生存期（PFS）和总生存期（OS）。结果2022年6月至2023年6月期间，共有11名患者接受了治疗（第1组：未接受过免疫疗法，n=9；第2组：曾接受过免疫疗法，n=2）；由于BA药物研发中止，试验已停止招募。未观察到任何客观缓解。在第1组中，8名可评估患者中有4名（50%）处于疾病稳定状态，其中3名的稳定状态持续时间较长；中位无进展生存期为3.7个月，中位总生存期尚未达到；其中1名疾病稳定的患者在68Ga-DOTATATE成像检查中显示出完全的代谢反应。在第2组中，有1名患者处于疾病稳定状态；中位无进展生存期为3个月，中位总生存期为6.8个月。有3名患者出现了3/4级的治疗相关不良反应（免疫介导的糖尿病、食管出血、贫血、鼻出血）。结论尽管未达到主要评估指标，但BA的安全性可控，部分患者因疾病长期处于稳定状态而获得临床益处，其中1名患者甚至出现了完全的代谢反应。这是首项针对R/M ONB患者的系统性疗法临床试验，证明了在该疾病背景下开展临床试验的可行性，也为进一步研究该患者群体的联合免疫疗法策略提供了依据。试验注册信息 ClinicalTrials.gov编号：NCT05012098，https://clinicaltrials.gov/ct2/show/NCT05012098。注册时间为2021年8月18日。背景对于患有复发性/转移性嗅神经母细胞瘤（ONB）的患者，目前尚无标准治疗方案，这是一种罕见的鼻窦肿瘤。我们开展了首项针对R/M ONB患者的免疫疗法临床试验（NCT05012098），旨在评估双功能TGF-β“陷阱”/抗PD-L1融合蛋白bintrafusp alfa（BA）的疗效。方法患者每两周接受一次BA治疗（1200毫克，静脉注射）。主要评估指标为总体缓解率（ORR）；次要评估指标包括安全性、无进展生存期（PFS）和总生存期（OS）。结果2022年6月至2023年6月期间，共有11名患者接受了治疗（第1组：未接受过免疫疗法，n=9；第2组：曾接受过免疫疗法，n=2）；由于BA药物研发中止，试验已停止招募。未观察到任何客观缓解。在第1组中，8名可评估患者中有4名（50%）处于疾病稳定状态，其中3名的稳定状态持续时间较长；中位无进展生存期为3.7个月，中位总生存期尚未达到；其中1名疾病稳定的患者在68Ga-DOTATATE成像检查中显示出完全的代谢反应。在第2组中，有1名患者处于疾病稳定状态；中位无进展生存期为3个月，中位总生存期为6.8个月。有3名患者出现了3/4级的治疗相关不良反应（免疫介导的糖尿病、食管出血、贫血、鼻出血）。结论尽管未达到主要评估指标，但BA的安全性可控，部分患者因疾病长期处于稳定状态而获得临床益处，其中1名患者甚至出现了完全的代谢反应。这是首项针对R/M ONB患者的系统性疗法临床试验，证明了在该疾病背景下开展临床试验的可行性，也为进一步研究该患者群体的联合免疫疗法策略提供了依据。试验注册信息 ClinicalTrials.gov编号：NCT05012098，https://clinicaltrials.gov/ct2/show/NCT05012098。注册时间为2021年8月18日。

免疫疗法临床结果临床3期临床2期

2026-05-27

·菲恩生物

【热门靶点解析】TGF-β信号通路+重要作用+药物研发！（建议收藏）

转化生长因子-β（TGF-β）是分泌型多肽生长因子家族的原型，由33个基因编码，参与调控细胞增殖、分化、迁移与凋亡，维持机体稳态。其家族分为经典TGF-β亚群（如TGF-β1-3、激活素等）和骨形态发生蛋白（BMP）亚群。其中，TGF-β1是研究最深入的亚型，在免疫细胞中广泛表达，具有强效促纤维化作用，几乎可由所有细胞合成。其基因位于19q3，编码产物在人与鼠间同源性高达99%，序列高度保守，功能相似，广泛参与组织修复、血管生成及免疫调节等生物学过程。 TGF-β1的激活 TGF-β1在体内以非活性前体蛋白形式合成，其翻译产物依赖信号肽引导并经分泌途径转运。前体蛋白在高尔基体中被前蛋白转化酶Furin特异性切割，生成Latency-Associated Peptide（LAP）与C端成熟肽段。两者通过非共价键紧密结合，形成无活性的复合物并分泌至胞外基质。该潜伏复合物需通过整合素等机制与LAP结合，诱导构象变化，从而释放具有生物活性的TGF-β1，启动下游信号通路，实现对细胞功能的调控。经典TGF-β/Smad信号转导 TGF-β的经典信号通路依赖R-Smad蛋白的磷酸化级联反应，分为TGF-β1/2/3和BMP两条分支，分别激活Smad2/3和Smad1/5/8。TGF-β配体首先结合Ⅱ型受体（TβRⅡ），招募Ⅰ型受体（TβRⅠ/ALK5）形成复合物，TβRⅡ磷酸化激活TβRⅠ，后者进一步磷酸化Smad2/3。活化的R-Smad与Smad4结合，转入细胞核，与转录因子共同调控靶基因表达，介导细胞分化、凋亡、上皮-间质转化及免疫调节等生物学功能。该过程受Ⅲ型受体（TβRⅢ）辅助调控，确保信号精确传递。 TGF-β1的重要作用 01、 TGF-β1定向诱导T细胞的分化 TGF-β1在免疫调控中具有双重作用：在IL-2存在下，高浓度TGF-β1促进CD4+T细胞分化为Foxp3+ iTreg细胞，维持免疫耐受；低浓度时则与IL-6或IL-21协同，通过STAT3信号诱导致病性Th17分化。其浓度依赖性效应还体现于抑制Th17特征或促进IL-23R表达。肿瘤微环境中，TGF-β1可诱导Treg分化，抑制CD8+ T细胞功能，助力肿瘤免疫逃逸。 02、 TGF-β1刺激成纤维细胞增殖 TGF-β1可促进成纤维细胞增殖、分泌胶原蛋白等细胞外基质，并抑制其降解，参与组织修复与纤维化。研究表明，10 ng/mL TGF-β1可显著增强L929细胞增殖。此外，TGF-β1能诱导骨髓间充质干细胞（BMSCs）向肌成纤维细胞分化，该过程伴随活性氧（ROS）大量生成。通过DCFH-DA荧光检测证实，TGF-β1处理后BMSCs内绿色荧光显著增强，表明其可诱导ROS产生，介导细胞分化。 TGF-β1调节骨代谢破骨细胞为源自单核造血细胞的多核巨细胞，负责骨吸收，其与骨形成的平衡维持骨骼稳态。TGF-β1在骨代谢中发挥双重调控作用：既可直接促进骨髓巨噬细胞向破骨细胞分化，又通过调节RANKL/护骨因子平衡间接影响其生成；同时，TGF-β1还能促进成骨细胞增殖，但抑制其向成熟骨细胞分化，在骨重塑中起关键调节作用，失衡则可能导致骨质疏松等疾病。靶向TGF-β的药物研发鉴于TGF-β在促进肿瘤转移中的关键作用，其抑制剂的研发备受关注。其中，抗体类药物因靶向性强、药代动力学优良而成为重点方向。目前开发的TGF-β靶向候选药物主要包括三类：靶向TGF-β的单克隆抗体、双特异性抗体以及基于TGF-β通路调控的细胞治疗产品，有望为癌症治疗提供新策略。 01、 TGF-β单抗靶向药 NIS793（诺华）为全人源抗TGF-β单抗，正开展针对胰腺癌等的III期临床。Galunisertib（礼来）是早期TGF-β抑制剂，已用于MDS、肝癌等临床研究。GFH018（劲方医药）为口服小分子抑制剂，联合PD-1抑制剂在全球多中心试验中。YL-13027（璎黎药业）具强效抗肿瘤活性，可增加肿瘤浸润淋巴细胞，与PD-L1抗体协同作用，现处于I期临床。 02、 TGF-β双抗靶向药靶向TGF-β的双抗药物是抗癌研发热点，尤以PD-L1/TGF-β双抗为主。默克/GSK的M7824曾因早期优异数据被视为“PD-1 2.0”，但在2021年多项关键临床试验失败后研发停滞，合作终止。尽管如此，国内企业持续推进，恒瑞医药的SHR-1701作为国内首款PD-L1/TGF-β双抗，目前有12项临床在研，多为联合疗法。此外，普米斯的PM8001、正大天晴的TQB2858和维立志博的LBL-015也进展较快，其中PM8001凭借单域抗体优势进入II期临床，展现国产创新潜力。 03 、靶向TGF-β的细胞治疗产品永泰生物的迪诺仑赛注射液是一款靶向CD19并拮抗TGF-β信号的CAR-T细胞治疗产品。改造后的T细胞可特异性杀伤CD19阳性肿瘤细胞，同时表达阻断TGF-β下游通路的蛋白，以抵御肿瘤微环境中的免疫抑制，防止CAR-T细胞功能耗竭。该产品旨在提升CAR-T在实体瘤中的持久性与疗效，克服现有治疗局限。临床应用 TGF-β1在多种病理生理过程中发挥关键作用：促进成纤维细胞迁移与基质沉积，加速创伤愈合；诱导上皮-间质转化，参与腹膜纤维化与心室重构；通过调控滋养细胞功能及氧化应激影响子痫前期发展；促进骨与牙本质再生，应用于活髓保存；在肿瘤中具双重作用，早期抑癌，晚期促侵袭转移及免疫逃逸。菲恩生物聚焦TGF-β靶点研究，依托先进的细胞与蛋白技术平台，提供经功能验证的重组TGF-β蛋白及其特异性抗体试剂，致力于为科研机构及生物医药企业提供高品质的科研工具，助力疾病机制研究。 >>>> 以下是菲恩生物 TGF-β 相关指标产品推荐 ELISA 试剂盒货号产品名称灵敏度检测范围 EH0287 Human TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-EH0287 Human TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml EM0176 Mouse TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-EM0176 Mouse TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml EMK0075 Monkey TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-EMK0075 Monkey TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml ERB0119 Rabbit TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-ERB0119 Rabbit TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml EP0154 Porcine TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-EP0154 Porcine TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml ER1378 Rat TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-ER1378 Rat TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml ESH0023 Sheep TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-ESH0023 Sheep TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml ECA0019 Canine TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-ECA0019 Canine TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml EGP0051 Guinea pig TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml QT-EGP0051 Guinea pig TGF-β1 QuickTest ELISA Kit 18.75pg/ml 31.25-2000pg/ml EHS0071 Horse TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml EU2686 Human/Mouse/Rat/Porcine/Canine TGF-β1 ELISA Kit 18.75pg/ml 31.25-2000pg/ml 重组蛋白&抗体货号产品名称表达宿主/宿主分子量/应用 P2940 Recombinant Human TGFB1 HEK293 cells 16,38,55 kDa P2602 Recombinant Mouse TGFB1 E.Coli 14.7 kDa P9633 Recombinant Mouse TGFB1 HEK293 cells 16, 8, 55 kDa P4827 Recombinant Rat Tgfb1 E.Coli 27.3 kDa FNab08638 TGFB1 antibody Rabbit ELISA,WB,IHC FNab09851 TGFB1 antibody Rabbit ELISA,WB GMP实验室公司介绍武汉菲恩生物科技有限公司(Wuhan Fine Biotech Co., Ltd.)面向国际市场专业研发、生产和销售ELISA试剂盒、抗体、蛋白及相关试剂。公司坐落于中国光谷生物城，建有现代化的研发中心和标准的GMP生产车间，已整体通过欧盟CE认证、ISO 9001:2015质量管理体系认证，获得高新技术企业、3551人才、瞪羚企业、科技小巨人等多项荣誉；公司建有实验动物房、配备先进的实验仪器，以保证产品的品质和实验研究的准确可靠性。公司由海内外博士、教授组成的研发和管理团队，拥有成熟的分子生物学技术、免疫学技术、蛋白表达纯化技术、抗体筛选及制备等生物学技术。现已研发生产ELISA试剂盒热门产品3000多种，包含10多种稀有种属试剂盒；鼠单抗，兔多抗一万余种经过验证的抗体，同时每年新增研发抗体近千种；多种标记/非标记二抗，针对兔、羊、小鼠、大鼠、人等多个种属。100多种标记二抗，标记物包括HRP、Biotin、FITC、Cy3、Alexa Fluor 488、Alexa Fluor 594等；提供蛋白产品7500多种，包括原核和真核表达重组蛋白以及天然蛋白，涵盖人类及常见种属的炎症因子，信号通路，诊断原料，受体蛋白，酶，抗原等。公司拥有一套严格的质控标准，生产出的产品均做过大量人和动物实验标本的检测。公司产品在免疫学、信号转导、代谢、神经科学等领域内都有最前沿科学文献发表，被国内外多所大学、研究机构和药学平台使用并发表文献达6500多次。公司凭借优异的产品和完善的服务体系受到国内外广大用户的青睐和认可；公司愿成为您的科研好帮手，专业生产商。 // END

100 项与必特芙普α 相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11893	-	-	DB15387

研发状态

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
肺癌	临床3期	美国	Merck KGaA	2021-12-01
肺癌	临床3期	中国	Merck KGaA	2021-12-01
肺癌	临床3期	日本	Merck KGaA	2021-12-01
肺癌	临床3期	比利时	Merck KGaA	2021-12-01
肺癌	临床3期	德国	Merck KGaA	2021-12-01
肺癌	临床3期	意大利	Merck KGaA	2021-12-01
肺癌	临床3期	俄罗斯	Merck KGaA	2021-12-01
肺癌	临床3期	韩国	Merck KGaA	2021-12-01
肺癌	临床3期	西班牙	Merck KGaA	2021-12-01
肺癌	临床3期	中国台湾	Merck KGaA	2021-12-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04835896 (K-Umbrella-06, ASCO2026)	临床1/2期	晚期胃癌二线 HER2-negative	30	Bintrafusp alfa (TGF-β trap/anti-PD-L1) + Paclitaxel	獵顧積齋鏇築製窪範廠(鑰鏇壓衊艱鑰積鹹網築): HR = 1.61, P-Value = 0.285 更多	积极	2026-05-29
				Nivolumab + Paclitaxel
NCT04789668 (CTgov)	临床1/2期	皮肤黑色素瘤 \| 转移性实体瘤 \| 血液肿瘤 ... 更多	8	Pimasertib+Bintrafusp Alfa (Dose-Level)	齋製鹹範窪壓餘鬱窪淵 = 艱壓蓋構淵簾壓衊衊窪製鏇鏇選鏇製夢獵鏇遞 (醖餘鹹鬱鹹鑰鑰醖壓積, 獵壓憲鏇願願鹽構顧糧 ~ 膚築鑰鹹齋製鑰襯遞築) 更多	-	2026-03-18
				Pimasertib+Bintrafusp (Dose-Level 1)	範選選淵繭艱夢夢範廠(遞觸醖齋壓壓積築憲鹽) = 淵鬱遞鬱鏇構衊簾淵鏇繭製窪醖蓋醖窪觸憲遞 (襯壓憲廠簾鬱齋醖餘鹽, 鹹鬱選鑰獵範蓋襯鏇襯 ~ 遞構繭構繭艱憲蓋窪壓) 更多
NCT04491955 (Pubmed \| Oncologist)	临床1/2期	转移性结直肠癌 pMMR	32	CV-301 + N-803 + bintrafusp alfa + PDS01ADC	憲顧製鬱築構築簾醖顧(衊遞壓憲糧淵觸鬱觸鹽) = 網構鹽範醖遞鏇獵觸範齋鹹壓遞餘構願顧憲淵 (選鹹獵膚壓衊繭夢憲築 ) 更多	不佳	2026-02-05
NCT05061823 (CTgov)	临床3期	肺癌	22	bintrafusp alfa (Biliary Tract Cancer)	構鏇廠齋鏇選齋構艱觸 = 壓遞齋獵壓簾觸膚鏇齋衊鑰壓醖願願鏇蓋醖構 (網鏇壓齋網窪簾積鹽糧, 壓蓋簾積築餘鬱製鏇築 ~ 顧憲廠蓋壓餘網襯選鬱) 更多	-	2026-02-02
				bintrafusp alfa (Non-small Cell Lung Cancer)	構鏇廠齋鏇選齋構艱觸 = 獵鏇鹹鏇窪艱淵鹽願糧衊鑰壓醖願願鏇蓋醖構 (網鏇壓齋網窪簾積鹽糧, 鑰遞醖顧衊鹽窪鏇糧襯 ~ 醖遞壓鬱糧遞憲艱鹹鹹) 更多
NCT05005429 (BIMES, CTgov)	临床2期	恶性胸膜间皮瘤	47	Bintrafusp alfa	淵壓簾齋網艱齋鏇憲窪(簾製衊簾獵廠簾遞窪構) = 艱夢鹹繭鏇憲壓餘簾淵遞壓壓衊膚餘鹹鏇遞範 (繭鹹淵選壓選網範壓觸, 鬱繭壓觸鹽網餘構網顧 ~ 遞繭鬱醖餘窪窪壓積鑰) 更多	-	2025-12-23
NCT04396535 (CTgov)	临床2期	晚期非小细胞肺癌	10	Bintrafusp Alfa+Docetaxel (Arm I (Docetaxel, Bintrafusp Alfa))	觸願膚網構築鹽獵廠獵(獵憲淵艱製鹹醖齋獵窪) = 簾鏇窪構遞願網簾鏇鹹鑰蓋鏇齋鬱齋鏇齋糧窪 (衊鏇窪淵餘選蓋築廠願, 觸夢構製鏇積廠鑰顧鹹 ~ 壓範範醖鹹範顧鹽憲遞) 更多	-	2025-11-17
				Docetaxel (Arm II (Docetaxel))	觸願膚網構築鹽獵廠獵(獵憲淵艱製鹹醖齋獵窪) = 鏇觸壓鹽積糧鹽膚壓觸鑰蓋鏇齋鬱齋鏇齋糧窪 (衊鏇窪淵餘選蓋築廠願, 壓鹹餘鹹簾艱淵積齋觸 ~ 遞鹹夢廠鏇顧淵範壓繭) 更多
NCT03493945 (QuEST1, SITC2025)	临床1/2期	去势抵抗性前列腺癌	37	BNVax+BA+NAI	夢艱網遞餘築遞鏇獵襯(艱鹹積壓襯鏇糧繭鬱壓) = 積繭鹽糧鹽糧窪夢網鏇壓簾積範襯積觸蓋積糧 (顧觸糧網選構遞範製鹽 )	积极	2025-11-05
NCT03493945 (QuEST1, CTgov)	临床1/2期	局部晚期恶性实体瘤 \| 晚期恶性实体瘤	59	castration+M7824+BN-Brachyury (Phase IIA Dose Expansion (Dose Exp.), Cohort 2, Arm 2.1A)	範積築餘鏇憲醖構醖齋 = 艱觸窪鹽衊壓鬱醖衊構簾憲顧餘壓製襯憲積夢 (壓網壓顧鹹製製繭窪鬱, 窪糧衊遞艱鹽餘蓋鹽醖 ~ 廠鏇鏇蓋願選憲齋構醖) 更多	-	2025-06-08
				N-803+M7824+BN-Brachyury (All Participants in Phase IIA Dose Expansion and Phase IIB Dose Expansion)	範積築餘鏇憲醖構醖齋 = 齋糧製觸鏇窪壓願遞齋簾憲顧餘壓製襯憲積夢 (壓網壓顧鹹製製繭窪鬱, 艱窪築鏇繭觸構顧獵鹹 ~ 鏇淵構簾積廠蓋糧願齋) 更多
ASCO2025	N/A	胃肠道肿瘤	938	Bintrafusp Alfa (M7824)	鑰壓憲餘獵簾艱願衊壓(鹽憲壓憲鹽鏇繭繭遞鏇) = Grade 3 or higher AEs were reported with an event rate of 28.8% (95% CI: 20.3-39.1%, p < 0.001), which decreased to 23.1% (p < 0.001) after excluding three studies, reducing heterogeneity to I² = 5.01% (p = 0.39) 糧製糧膚範觸夢醖築積 (蓋觸壓範鏇鏇願鬱鏇鏇 )	积极	2025-05-30
NCT04287868 (Company_Website \| Pubmed) 人工标引	临床1/2期	HPV相关癌症 HPV16-positive	50	PDS0101 + PDS01ADC + bintrafusp alfa (BA) (ICB naïve patients)	膚壓繭醖選蓋襯獵夢網(製艱築膚膚淵鬱觸獵糧) = 鹹鏇選築製網構壓鏇鏇積選膚鏇顧艱淵獵顧夢 (觸獵獵遞構壓範醖觸築, 8.3 ~ NE) 更多	积极	2025-02-26
				PDS0101 + PDS01ADC + bintrafusp alfa (BA) (ICB naïve patients + HPV16-positive)	膚壓繭醖選蓋襯獵夢網(製艱築膚膚淵鬱觸獵糧) = 網顧製膚簾淵觸鑰鑰糧積選膚鏇顧艱淵獵顧夢 (觸獵獵遞構壓範醖觸築, 9.0 ~ 21.3) 更多