A Phase 1/2, Open-label, Global, Multicenter, Dose-Escalation and Dose-Expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Combination With Pembrolizumab in Participants With Advanced Solid Tumors

The primary objective of this study is to determine the recommended Phase 2 doses (RP2D(s)) and maximum tolerated dose (MTD) of PYX-201 in combination with pembrolizumab for participants with advanced solid tumors.

开始日期2025-04-15

申办/合作机构

Pyxis Oncology, Inc.

[+1]

NCT05720117

/ Recruiting临床1期

A First-in-Human, Open-label, Multicenter, Phase 1 Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of PYX-201 in Participants With Advanced Solid Tumors

The primary objectives of this study are to determine the recommended dose(s) of PYX-201 for participants with relapsed/refractory (R/R) solid tumors, and to determine the objective response rate (ORR) in participants treated with PYX-201 as a single agent.

开始日期2023-03-14

申办/合作机构

Pyxis Oncology, Inc.

100 项与 Micvotabart pelidotin 相关的临床结果

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100 项与 Micvotabart pelidotin 相关的转化医学

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100 项与 Micvotabart pelidotin 相关的专利（医药）

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项与 Micvotabart pelidotin 相关的文献（医药）

2025-05-08·JOURNAL OF MEDICINAL CHEMISTRY

Antibody-Drug Conjugates of NLRP3 Agonists: How Overcoming Lysosomal Accumulation Necessitated Noncanonical Linker Attachments

Article

作者: Lo, Julian C. ; Verma, Isha ; Su, Yang ; Chekler, Eugene P. ; Deshpande, Madhura ; D’Souza, Ryan ; Kotapati, Srikanth ; Riehl, Paul S. ; Zhang, Meng Yao ; Pan, Jie ; Dhar, Payal ; Olsen, Jonathan ; Wang, Zhiying ; Janc, James ; Yamazoe, Sayumi ; Zhang, Jun ; Li, Yi-xin ; Johnson, Walter L. ; Broz, Miranda ; Hollingsworth, Scott A. ; Zhang, Qian ; Li, Yvonne ; Micci, Luca ; Mansfield, Kathleen ; Cheng, Qinqin

An initial series of NLRP3 agonist antibody-drug conjugates (ADCs) failed to induce IL-1β in vitro due to lysosomal trapping of the payload. To address this, we developed assays and computational tools to identify a new payload that could diffuse out of the lysosomes. ADCs derived from this payload were active, emphasizing the need to avoid payload lysosomal accumulation for nonlysosomal targets. Two active ADCs necessitated attaching a cleavable valine-citrulline recognition element to the payload via a noncanonical ester linkage, rather than a canonical carbamate one, since the payload did not contain a basic amine. The citrulline stereocenter configuration was found to affect the payload release and in vitro activity. The ADC with the (L)-Val-(L)-Cit ester configuration showed superior in vitro activity, high stability in mouse serum, and rapid cleavage in human liver lysosomes. These properties suggest that this noncanonical (L)-Val-(L)-Cit ester attachment may be valuable to the ADC community moving forward.

2025-02-01·TETRAHEDRON

Drug-linker constructs bearing unique dual-mechanism tubulin binding payloads tethered through cleavable and non-cleavable linkers

Article

作者: VanNatta, Jennifer M ; Bai, Ruoli ; Deng, Yuling ; Trawick, Mary Lynn ; Ford, Jacob W ; Mondal, Deboprosad ; Lin, Chen-Ming ; Pinney, Kevin G ; Hamel, Ernest

Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels. These payloads have been incorporated into a variety of drug-linker constructs utilizing the clinically relevant cathepsin B cleavable Val-Cit dipeptide linker, employed within several FDA approved ADCs, along with other non-cleavable constructs. Various synthetic strategies were evaluated to prepare these drug-linker constructs. Aniline-based payloads were incorporated utilizing the Val-Cit dipeptide linker similar to FDA approved ADCs such as Adcetris^® (brentuximab vedotin). An additional self-immolative group, previously described in the literature for related model systems, was employed to tether the phenolic payloads. A variety of drug-linker constructs (with each bearing a unique dual mechanism payload) were synthesized and evaluated biologically for their enzyme-mediated release of payload and inhibition of tubulin polymerization. Following deactivation of the highly electrophilic maleimido terminus as its corresponding N-acetyl cysteine (NAC) derivative, the most promising construct (NAC-4) demonstrated approximately 90% release of an aniline-functionalized payload (1) upon treatment with cathepsins B or L over 90 minutes. Building on these promising results, future studies will examine the conjugation of drug-linker construct 4 to selected antibodies and engineered proteins and evaluate the biological activity of the resultant antibody-drug conjugates (ADCs).

2024-10-24·JOURNAL OF MEDICINAL CHEMISTRY

Exo-Cleavable Linkers: Enhanced Stability and Therapeutic Efficacy in Antibody–Drug Conjugates

Article

作者: Tatsuya Okuzumi ; Noriko Hatada ; Naoko Arashida ; Tomohiro Fujii ; Tomohiro Watanabe ; Yusuke Iwai ; Yutaka Matsuda ; Kazutaka Shimbo ; Natsuki Shikida ; Akira Nakayama ; Ryusuke Hirama ; Kenichiro Ito ; Takuya Seki ; Arashida, Naoko

Antibody-drug conjugates (ADCs) combine cytotoxic payloads with monoclonal antibodies through chemical linkers. Finding linkers that both enhance circulatory stability and enable effective tumor payload release remains a challenge. The conventional valine-citrulline (Val-Cit) linker is associated with several inherent drawbacks, including hydrophobicity-induced aggregation, a limited drug-antibody ratio (DAR), and premature payload release. This study introduces an exolinker approach, repositioning the cleavable peptide linker at the exo position of the p-aminobenzylcarbamate moiety, as an advancement over conventional linear linkers. This design, which incorporates hydrophilic glutamic acid, addresses the limitations of the Val-Cit platform and improves the ADC in vivo profiles. In vitro and in vivo evaluations showed that exolinker ADCs reduced premature payload release, increased drug-to-antibody ratios, and avoided significant aggregation, even with hydrophobic payloads. Furthermore, the payload remained stably attached to the ADC even in the presence of enzymes like carboxylesterases and human neutrophil elastase, indicating the potential for a favorable safety profile.

项与 Micvotabart pelidotin 相关的新闻（医药）

2026-02-26

·PRNewswire

Head and Neck Cancer Therapeutics Market to Reach USD 2.6 Billion by 2032, Driven by Immunotherapy and Precision Oncology - Credence Research Inc.

LONDON, Feb. 26, 2026 /PRNewswire/ -- The "Head and Neck Cancer Therapeutics Market – Growth, Share, Opportunities & Competitive Analysis, 2024 – 2032" report has been added to the offering of Credence Research Inc. The global head and neck cancer therapeutics market is projected to grow from USD 1.58 billion in 2024 to USD 2.6 billion by 2032, reflecting a CAGR of 6.8% over 2024–2032. Growth is supported by rising incidence, expanding use of immunotherapy and targeted therapies, and broader adoption of precision medicine, subject to access and reimbursement constraints across regions. Key Attributes Historical Period: 2020–2023 Base Year: 2024 Forecast Period: 2025–2032 Head and Neck Cancer Therapeutics Market Size 2024: USD 1.58 Billion Head and Neck Cancer Therapeutics Market Size 2032: USD 2.6 Billion Head and Neck Cancer Therapeutics Market CAGR (2024–2032): 6.8% Access crucial information at unmatched prices! Request your sample report today and start making informed decisions powered by Credence Research Inc. - Rising Prevalence of Head and Neck Cancers Higher prevalence and diagnosis rates of head and neck cancers underpin demand for therapeutics. Tobacco use, alcohol consumption, and HPV infection remain key risk factors in many markets. Some public health agencies report that HPV accounts for a substantial share of throat and mouth cancers, reshaping incidence patterns by subsite and region. These factors expand the treated population and support demand across first-line, recurrent, and metastatic care settings. Population aging further increases risk in many countries, adding to the addressable patient base. However, treatment uptake still depends on stage at diagnosis, timely referral to specialist centers, and patient ability to access and afford care. Advancements in Targeted and Immunotherapy Treatments Targeted therapies and immunotherapies have broadened the available treatment toolkit, particularly in recurrent or metastatic disease and biomarker-defined subgroups. EGFR-directed approaches and monoclonal antibodies are used in certain regimens. Checkpoint inhibitors, including pembrolizumab, have shown survival benefits in selected populations. These modalities can offer different efficacy and safety profiles versus conventional chemotherapy. Clinical benefit, though, varies by tumor type, line of therapy, biomarker status, and patient health. Ongoing clinical trials and label expansions continue to adjust where and how these agents are positioned within treatment pathways. Growing Adoption of Immunotherapy Immunotherapy is becoming a key component of the head and neck cancer treatment landscape. Immune checkpoint inhibitors and other immune-based approaches are gaining traction due to their ability to boost anti-tumor immune responses and extend survival in certain settings. For instance, GeoVax's Phase 2 trial of gene therapy Gedeptin combined with pembrolizumab (Keytruda) in recurrent head and neck cancer aims for pathologic complete responses in 36 patients, reflecting growing interest in immune-based strategies. Regulatory approvals and expanding clinical experience have supported the inclusion of immunotherapy in more treatment protocols. This trend reflects a broader shift in oncology toward immune-modulating approaches, although cost and eligibility criteria still constrain uptake. Market Challenges High Treatment Costs The high cost of advanced treatment options remains a major restraint. Immunotherapies, targeted therapies, and precision diagnostics often carry substantial price tags, which can limit access for many patients, especially in low- and middle-income regions. Expenses from prolonged therapies, companion diagnostics, and supportive care add further burden to patients and health systems. This financial pressure can constrain adoption, even where clinical benefit is demonstrated. Limited Access to Advanced Healthcare Infrastructure Access to specialized oncology services remains uneven. Many patients in developing and underdeveloped regions cannot reach centers that provide advanced therapies or complex diagnostics. Rural areas face gaps in diagnostic capacity, specialist availability, and timely referrals. This imbalance contributes to late-stage diagnosis and reduces the effectiveness of available interventions. The disparity in infrastructure and trained personnel remains a significant barrier to broader adoption of advanced therapeutics. Market Opportunities The increasing adoption of precision medicine presents a key opportunity. Advances in genomic profiling and biomarker identification support development of targeted therapies and more personalized regimens. Tailored treatment strategies can improve clinical outcomes and reduce unnecessary exposure to less effective options. Growing use of immunotherapy and combination regimens offers further opportunity. Integrating checkpoint inhibitors and other immune-based therapies with established treatments can improve survival and address resistance patterns. Firms that focus on novel combinations and biomarker-guided approaches can capture new growth segments. Improving healthcare infrastructure and access in emerging markets also expands opportunity. Investments in oncology centers, diagnostics, and reimbursement schemes can unlock new demand. Strategic collaborations, local trials, and adaptive pricing models can help companies build presence in these regions. Market Segmentation By Therapy Type Chemotherapy Immunotherapy Targeted Therapy By Route of Administration Injectable Oral By Distribution Channel Hospital Pharmacies Retail and Specialty Pharmacies Online Pharmacies By Region North America: United States, Canada Europe: United Kingdom, Germany, France, and others Asia-Pacific: China, India, Japan Latin America: Brazil, Mexico Middle East and Africa: South Africa, United Arab Emirates, and others Browse Complete Report Originally Published by Credence Research - Regional Analysis North America North America is described as accounting for around 40% of global revenue. The region benefits from established oncology infrastructure, high adoption of advanced therapies, and strong clinical research activity. Some sources cite more than 65,000 new head and neck cancer cases per year, supporting consistent treatment demand. Uptake of checkpoint inhibitors such as pembrolizumab and nivolumab has influenced treatment patterns in eligible patients. Reimbursement policies play a central role in shaping access and choice of therapy. Europe Europe is described as contributing around 30% of global share. Public health coverage, oncology research funding, and awareness campaigns support early detection and treatment access. Annual incidence is cited at more than 150,000 cases, with rising HPV-linked disease reported in some subtypes. EU-level initiatives and national programs support personalized medicine and development of novel therapies. Vaccination and prevention may affect long-term incidence, but near-term demand is driven by existing diagnosed populations. Key Player Analysis AstraZeneca Bristol-Myers Squibb Company Clinigen Group plc. Coherus BioSciences Eli Lilly and Company Hoffmann-La Roche Ltd. Merck & Co. Sanofi Takeda Pharmaceutical Company Limited Teva Pharmaceutical Industries Ltd Recent Developments In February 2025, Merus N.V. reported that the U.S. FDA granted Breakthrough Therapy Designation for petosemtamab in combination with pembrolizumab for first-line treatment of adults with recurrent or metastatic PD-L1–positive head and neck squamous cell carcinoma (CPS ≥ 1). In March 2025, Aprea Therapeutics signed a Material Transfer Agreement with MD Anderson Cancer Center to evaluate its WEE1 inhibitor, APR-1051, in HPV-positive and HPV-negative head and neck cancers. The work includes preclinical studies on replication stress and evaluation of combination strategies, including with immune checkpoint inhibitors. In April 2025, Akeso, Inc. received U.S. FDA approval for penpulimab-kcqx (a PD-1 monoclonal antibody) in combination with cisplatin or carboplatin and gemcitabine for adult recurrent or metastatic non-keratinizing nasopharyngeal carcinoma (NPC). In June 2025, Exelixis discontinued development of zanzalintinib for advanced head and neck cancer, citing a more competitive FGFR-inhibitor landscape. In June 2025, the U.S. FDA approved peri-operative pembrolizumab following KEYNOTE-689 results reporting event-free survival benefit. In July 2025, Rakuten Medical, Inc. expanded patient recruitment to Japan and reported plans to expand to Eastern Europe for its Phase 3 ASP-1929 photoimmunotherapy program in combination with pembrolizumab as first-line therapy for recurrent head and neck squamous cell carcinoma. In September 2025, Transgene reported positive Phase 1 results for TG4050 in operable head and neck squamous cell carcinoma. In October 2025, Bicara Therapeutics, Inc. reported that the U.S. FDA granted Breakthrough Therapy Designation for ficerafusp alfa in combination with pembrolizumab for first-line treatment of head and neck squamous cell carcinoma (HNSCC). In December 2025, Pyxis Oncology reported positive preliminary Phase 1 data for micvotabart pelidotin (MICVO) in patients with recurrent or metastatic head and neck squamous cell carcinoma. Report Coverage The research report offers an in-depth analysis by Therapy Type, Route of Administration, and Distribution Channel. It profiles leading market players, outlining their business overviews, product portfolios, investment focus, revenue streams, and key applications. The report also examines the competitive environment, SWOT positions, key market trends, and primary drivers and restraints. It reviews market dynamics, regulatory frameworks, and technological advances shaping the sector. The analysis includes assessment of macroeconomic factors and healthcare system changes affecting demand. Finally, the report provides strategic recommendations for new entrants and established companies to navigate regulatory complexity, optimize portfolios, and capture growth opportunities in both mature and emerging markets. Browse Complete Report Originally Published by Credence Research - Related Reports – Neoantigen-Based Personalized Cancer Therapeutic Vaccines Market Colorectal Cancer Therapeutics Market Head and Neck Cancer Therapeutics Market Lung Cancer Therapeutics Market Cancer Therapeutics Market Checkpoint Inhibitor Refractory Cancer Market Antisense RNAi Therapeutics Market U.K. Monoclonal Antibodies Therapeutics Market Italy Monoclonal Antibodies Therapeutics Market France Monoclonal Antibodies Therapeutics Market Europe Monoclonal Antibodies Therapeutics Market Australia Monoclonal Antibodies Therapeutics Market U.S. Monoclonal Antibodies Therapeutics Market mRNA Therapeutics Market Brain Metastasis Therapeutics Market About Us Credence Research Inc is a global market intelligence and consulting firm founded in 2015. It delivers deep market insights, quantitative analysis, and strategic guidance to business leaders, investors, governments, NGOs, and non-profit groups worldwide. The company helps organizations evaluate markets, understand trends, reduce risk, and make data-driven decisions that support growth and competitive strategy. Credence Research is known for rigorous research methods and comprehensive analytics. The firm produces detailed reports covering market size, forecasts, growth drivers, trends, and competitive landscapes across many industries. Each report often includes frameworks like PESTLE and Porter's Five Forces to give a complete view of market dynamics and future potential. Credence Research also provides tailored consulting services, due diligence support, go-to-market planning, and pre-IPO research to strengthen client strategies and investment narratives. Its insights come from both primary and secondary research, expert interviews, and advanced data modelling. The firm's client base spans Europe, the Americas, Asia-Pacific, and the Middle East/Africa. To find out more, visit or follow us on X.com, LinkedIn and Facebook Contact Us – Credence Research Inc, Tower C-1105, S 25, Akash Tower, Vishal Nagar, Pimple Nilakh, Haveli, Pune – 411027, India USA: +1-888-600-6441 Email: [email protected] Visit Our Website: Logo - SOURCE Credence Research Inc. 21% more press release views with Request a Demo

免疫疗法上市批准临床结果临床2期突破性疗法

2026-02-22

·科学研读社

抗体-药物偶联物（ADC）格局分析：下一代技术如何突破现有瓶颈

抗体-药物偶联物（Antibody–drug conjugates, ADCs）已成为肿瘤学领域的一种关键治疗方式，其在多种适应症中展现出优秀的临床表现。预计到2028年，已获批ADC及处于III期开发阶段的ADC所产生的收入将达到260亿美元。尽管ADC取得了成功，但其应用的长期增长仍面临两大主要挑战。首先，经过验证的有效载荷作用机制（MoAs）数量有限，限制了可治疗的适应症范围。已获批的ADC载荷涵盖三种细胞毒作用机制（抗微管、DNA烷化和拓扑异构酶1抑制）这些机制通常要求肿瘤特异性地过表达靶抗原，以确保充分且安全的载荷递送。因此，这些ADC主要针对已确立的肿瘤抗原，如HER2、CD20和BCMA。其次，非特异性和不足的载荷递送缩小了ADC的治疗窗口。已获批ADC的递送组件通常包括通过半胱氨酸还原随机偶联到单克隆抗体载体上的可裂解肽连接子。载荷提前释放、肿瘤穿透性差、药物抗体比（DAR）可变以及聚集是常见问题。为了探索下一代ADC技术对这些挑战的影响，本文分析了ADC临床管线在五个设计维度（靶点、有效载荷MoA、抗体、连接子和偶联方法）方面的创新，并讨论其扩大可治疗适应症或拓宽ADC治疗窗口的可能性。临床管线分析根据克服上述两大挑战的潜力，将正在开发的ADC资产分为两种类型。1型项目（Type-1 assets）具有新靶点和/或新有效载荷MoA，具有首创（first-in-class）潜力。2型项目（Type-2 assets）利用已确立的靶点/有效载荷MoA组合，辅以新颖的递送组件，以实现同类最优（best-in-class）的特征。第一三共（Daiichi Sankyo）的patritumab deruxtecan（靶向HER3）是1型项目的一个例子。II期HERTHENA-Lung01试验的最新数据显示，在既往接受过EGFR抑制剂和铂类化疗的EGFR突变患者中，其客观缓解率（ORR）为30%，而类似患者群体的真实世界估计ORR为14%。默克（Merck）和科伦生物（Kelun Biotech）的SKB264是2型项目的一个例子，其靶点和有效载荷MoA与已获批的ADC sacituzumab govitecan（Trodelvy；吉利德）相同。SKB264的差异化2-甲磺酰基嘧啶连接子相比sacituzumab govitecan提高了循环稳定性。一项针对经治转移性三阴性乳腺癌患者的II期研究显示，SKB264的ORR为40%，56%的患者出现3级或以上的不良事件（AEs）。相比之下，sacituzumab govitecan在类似患者群体中报告的ORR为21%，AE发生率为74%。在目前168个临床开发阶段ADC中，约85%的项目针对实体瘤适应症，其中乳腺癌和肺癌最为常见。在III期ADC中，约60%是2型项目，它们利用已确立的靶点和有效载荷MoA，并配以改进的递送组件，这可能反映了该模式近期的成功以及晚期开发中较低的风险容忍度。更大的生物学风险体现在早期开发阶段；约75%的I/II期ADC是1型项目，具有新颖的靶点和作用机制组合。下图展示了ADC临床管线在五个设计维度（靶点、有效载荷MoA、抗体、连接子和偶联方法）的前十靶点或技术。下一代靶点分析生物靶点是ADC的一个主要创新领域，目前临床上有61个独特靶点正在被研究。总体而言，约90%的靶点是癌细胞上高表达的抗原，而约10%的靶点与肿瘤微环境的独特特征相关。例如，Pyxis Oncology公司的PYX-201靶向纤连蛋白（fibronectin），这是一种由癌症相关成纤维细胞大量分泌的细胞外蛋白。靶向基质成分的ADC可能对基质-肿瘤比例高的肿瘤（如乳腺癌和前列腺癌）有效，并且由于基质细胞的遗传稳定性，可以消除耐药性的演变。下一代技术分析为了衡量ADC创新的潜在影响，我们对下一代技术进行了分类，并将其特征与已上市的ADC进行了比较（图2）。同时重点介绍了一部分因其新颖性和/或有前景的临床前和临床数据而可能值得关注的下一代设计杠杆。图2 | 下一代ADC技术的评估下一代有效载荷（Next-gen payloads）小分子降解剂是一类有前景的有效载荷，因其高特异性、皮摩尔级效力以及能够靶向与癌症相关的广泛胞内蛋白。Orum Therapeutics公司的ORM-5029递送一种选择性靶向GSPT1（一种在胃癌、结直肠癌和乳腺癌等多种癌症中过表达的GTP酶）的降解剂有效载荷。在乳腺癌模型的临床前研究中，其抗癌活性与trastuzumab deruxtecan（Enhertu；第一三共）相似。ORM-5029即将公布的I期数据将是抗体-降解剂偶联物的首个临床数据。下一代载体（Next-gen carriers）对抗体进行工程化改造，使其具有可变的抗原结合亲和力，可以减少脱靶组织毒性并增加肿瘤特异性暴露。策略包括使用可被肿瘤中过表达的蛋白酶切割的肽掩蔽物来屏蔽Fab结构域，以及对抗体进行工程化改造以优化其pH敏感的结合特性。尽管过去曾有失败案例，但抗体工程化有望拓宽治疗窗口，并治疗靶点表达水平较低的患者。例如，Mythic Therapeutics公司的MYTX-011被设计为在内体pH下具有较低的抗原亲和力，以增强载荷从内体逃逸的能力。在临床前研究中，其在c-Met表达的肿瘤模型中显示出比亲本抗体和一款临床c-Met靶向ADC更高的内化率、细胞毒活性和体内疗效。下一代连接子（Next-gen linkers）新兴的连接子技术专注于独立于内源性酶介导裂解的受控载荷释放。TagWork公司的临床前ADC TGW101使用一种外源性给药的化学激活剂来诱导载荷释放。在结直肠癌和卵巢癌异种移植模型的临床前研究中，其抗肿瘤活性优于VC-肽连接子。受控的载荷释放可以限制脱靶组织毒性，并支持进一步开发靶向癌症中过表达的非内化蛋白的资产。下一代偶联（Next-gen conjugation）将非天然氨基酸整合到抗体载体中，可通过肟键实现位点特异性偶联。Ambrx公司的ARX788是一种HER2靶向ADC，其不可裂解的PEG连接子以位点特异性的方式连接到非天然氨基酸上。I期数据显示，其抗肿瘤活性和血清稳定性均优于已获批的HER2靶向ADC。减少载荷的提前释放可以增加递送至肿瘤细胞的药量，并推动更高的缓解率。结语随着ADC获得认可和新技术的涌现，企业需要审慎评估这些新兴平台，明确自身是走“首创”还是“同类最优”的战略路径，以最大化其专业技术能力和投资回报。而ADC领域正处于一个由技术创新驱动的关键转折点。未来不太可能出现一种“放之四海而皆准”的通用技术平台。相反，成功的公司将会构建一个多样化的技术组件库（包括多种靶点、载荷、抗体、连接子和偶联方法），并根据特定靶点和适应症的需求，像“搭积木”一样进行灵活组合，实现“即插即用”（plug-and-play）式的定制化ADC开发。这种策略不仅能有效克服现有ADC的两大核心挑战，还将极大地加速新药研发进程，最终惠及更广泛的患者。往期精选文章：世界艾滋病日：抗体与T细胞联手实现持久的HIV缓解多特异性抗体（PolyBodies）治疗呼吸道合胞病毒（RSV）感染的展望 NATURE: 抗体药物新前景---对抗禽流感和HIV

抗体药物偶联物临床2期引进/卖出临床结果申请上市

2026-02-16

·生物药观察

靶向肿瘤微环境靶点的非内化ADC PYX-201

今天除夕，祝大家新春快乐今天聊一款非内化ADC，即通过靶向肿瘤微环境靶点并在胞外释放的新型ADC PYX-201（Micvotabart pelidotin，简写MICVO）。 MICVO由Pyxis Oncology 开发，目前正在开展HNSCC的单用及K药联用临床I期研究。 MICVO的分子设计： 🎯EDB+FN靶点：纤连蛋白的外域-B 剪接变体（EDB⁺FN）是纤连蛋白的一种剪接异构体。纤连蛋白是一种仅在多种实体瘤基质中表达上调的基质蛋白，与肿瘤生长、血管生成及转移密切相关，在正常组织低表达。在肿瘤细胞内和细胞膜上不表达，在肿瘤基质中特异性表达，因此属于肿瘤微环境的靶点 💊载荷：微管抑制剂Auristatin-0101，DAR4设计丫抗体：anti-EDB+FN-K(94)R-huIgG1-K290C-κK183C，工程化的半胱氨酸实现定点偶联 🔗连接子：传统连接子mc-vc-pab，作为一款first-in-concept 的ADC，并没有针对肿瘤微环境对连接子进行优化，不过体外研究证实多种组织蛋白酶可以有效释放载荷，且肿瘤微环境的低pH更容易释放载荷。 🐓proposed MOA：1)载荷释放后直接杀伤肿瘤；2)旁观者效应杀伤；3) ICD效应杀伤。 💯潜在优势：靶点特异性强，安全性更好；可以穿过肿瘤的纤维化屏障，药效更优（At ESMO, Tolcher emphasized that Micvo’s extracellular-targeting approach could bypass the fibrotic barriers of tumors like pancreatic cancer and enable a potent bystander effect，未看到相关证据） 🐭药效学研究中，多种PDX模型观察到显著药效，和PD-1具有协同优势 👤临床研究： I期剂量爬坡研究中，有效剂量为3.6-5.4mpk，在此剂量范围内ORR=26%，HNSCC的ORR为50%（2PR，1CR），DCR 100%，2例更高剂量6.6mpk 均为SD。安全性方面，在3.6-5.4mpk剂量范围内，无治疗相关性死亡，但是5.4mpk出现多例给药终止，剂量减少和延迟给药。3-4级AE主要为皮肤、中性粒细胞减少，贫血，还有1例肺炎。 MICVO显著增加了淋巴细胞的浸润靶点表达和药效并没有显著的相关性 HNSCC的结构特征可能和药效有一定相关性总结：靶向肿瘤微环境ADC是一种比较好的差异化思路，有些靶点如LRRC15在肿瘤细胞和肿瘤微环境同时表达，靶向肿瘤微环境Treg的CCR8 ADC，靶向肿瘤相关成纤维细胞的FAP ADC等也在POC阶段。MICVO目前的数据还比较有限，安全性和有效性的平衡点，肿瘤标志物和药效的相关性等都需要深入研究，期待更多研究结果。关注小编不迷路参考文献 1MICVO AACR_2024_Poster_PYX-201_a_stroma-targeting_ADC.pdf 2 MICVO AACR_2024-Poster_Sara_Final_2.pdf 3 MICVO AACR_NCI_EORTC_immune_intfilt_2025_EL_Final.pdf 4 MICVO AACR-NCI-EORTC-2025_CS_Final.pdf 5 MICVO ESMO-2025-Poster_Final__07Oct2025_print_Sized.pdf 6 MICVO ESMO-2025-Poster-1014e-IHC_FINAL-1.pdf

临床1期抗体药物偶联物AACR会议临床结果

100 项与 Micvotabart pelidotin 相关的药物交易

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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
晚期恶性实体瘤	临床2期	美国	Pyxis Oncology, Inc.	2025-04-15
晚期恶性实体瘤	临床2期	西班牙	Pyxis Oncology, Inc.	2025-04-15
乳腺癌	临床前	美国	Pyxis Oncology, Inc.	2025-04-28
胰腺癌	临床前	美国	Pyxis Oncology, Inc.	2023-05-03

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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


NCT05720117 (Company_Website \| NEWS) 人工标引	临床1期	转移性头颈部鳞状细胞癌 \| 复发性头颈部鳞状细胞癌	18	Micvotabart Pelidotin 5.4 mg/kg	網窪鹽簾壓積蓋夢窪範(鬱願膚壓願醖膚鹹積遞) = 襯繭鏇鏇觸餘鹹鏇齋鑰夢選繭糧憲鏇壓鹽顧鑰 (憲壓憲艱艱觸選窪獵壓 ) 更多	积极	2025-12-18
NCT05720117 (Company_Website \| NEWS) 人工标引	临床1期	转移性头颈部鳞状细胞癌 \| 复发性头颈部鳞状细胞癌	18	Micvotabart Pelidotin 5.4 mg/kg (post platinum & anti-PD(L)-1 experienced patients)	網窪鹽簾壓積蓋夢窪範(鬱願膚壓願醖膚鹹積遞) = 遞餘選繭廠糧積齋淵鹽夢選繭糧憲鏇壓鹽顧鑰 (憲壓憲艱艱觸選窪獵壓 )	积极	2025-12-18
NCT06795412 (Company_Website \| NEWS) 人工标引	临床1/2期	转移性头颈部鳞状细胞癌 \| 复发性头颈部鳞状细胞癌	7	MICVO +KEYTRUDA	簾獵鏇餘選壓構廠壓構(選憲糧製遞艱遞餘齋鏇) = 夢構夢糧醖選襯夢網壓觸簾鬱襯顧簾積鹹鑰簾 (窪艱齋窪膚築鹽膚遞蓋 ) 更多	积极	2025-12-18
NCT06795412 (PYX-201-102, SITC2025)	临床1/2期	晚期头颈部鳞状细胞癌一线	60	PembrolizumabMicvo (PYX-201) + PembrolizumabMicvo (PYX-201)	艱顧壓窪廠餘壓範鹹齋(網築積襯廠範襯壓獵網) = 遞鏇遞鑰繭鬱壓遞淵窪夢衊艱蓋顧築製願願積 (觸窪艱窪蓋製醖鹽構鏇 ) 更多	积极	2025-11-05
NCT05720117 (PYX-201-101, ESMO2025)	临床1期	实体瘤	77	MICVO	廠鹽淵繭鏇鏇衊膚窪糧(簾鬱膚艱網壓襯製壓簾) = 壓衊鬱糧淵鹹積衊衊選鏇餘簾鏇簾選簾築鹽網 (範衊艱繭壓鏇憲範範積 ) 更多	积极	2025-10-17
NCT06795412 (PYX-201-102, ESMO2025)	临床1/2期	晚期恶性实体瘤二线 \| 一线	32	MICVO + Pembrolizumab (PD-L1 CPS ≥1 + Advanced solid tumors)	簾鹹壓壓構蓋襯憲夢夢(艱憲夢繭齋鏇鏇醖膚簾) = 衊築願築餘鏇廠衊糧築廠顧範繭衊餘鏇繭顧淵 (積顧觸網糧願壓鬱淵遞 ) 更多	积极	2025-10-17
NCT05720117 (GlobeNewswire) 人工标引	临床1期	实体瘤 \| 头颈部鳞状细胞癌	80	PYX-201 (HNSCC)	齋鏇糧醖簾選廠鹹淵選(獵範淵製遞願膚憲蓋簾) = 糧構鬱餘憲衊淵蓋艱鹽餘窪繭選膚選鹽淵願選 (餘壓醖顧顧襯廠餘廠觸 ) 更多	积极	2024-11-20
NCT05720117 (GlobeNewswire) 人工标引	临床1期	实体瘤 \| 头颈部鳞状细胞癌	80	PYX-201 (six Solid Tumor Types)	齋鏇糧醖簾選廠鹹淵選(獵範淵製遞願膚憲蓋簾) = 鬱廠願繭鹹繭齋窪襯淵餘窪繭選膚選鹽淵願選 (餘壓醖顧顧襯廠餘廠觸 )	积极	2024-11-20