An Open-label Pilot Study to Evaluate the Safety and Efficacy of ADCT-301 in Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Myeloproliferative Neoplasms.

This is research study to find out if a drug called ADCT-301 is safe and to look at how patients respond to the study drug after an allogeneic transplantation.
ADCT-301 will be administered on Days 1, 8 and 15 with blood tests following study drug infusion. Patients will have a bone marrow biopsy at the end of cycle 2/before cycle 3 to see how they are responding to the study drug.
Patients will be followed for approximately every 12 weeks from the last disease assessment for up to 1 year from completion of therapy.
There are risks to this study drug. Some risks include: decrease in certain blood cells, weight loss, loss of appetite, rash and Guillain-Barre syndrome, where the immune system attacks and damages nerves.

开始日期2021-12-07

申办/合作机构

Duke University

[+1]

NCT04052997

/ Completed临床2期

A Phase 2, Open-Label, Single-Arm Study to Evaluate the Efficacy and Safety of Camidanlumab Tesirine (ADCT-301) in Patients With Relapsed or Refractory Hodgkin Lymphoma

The purpose of this study is to evaluate the clinical efficacy and safety of Camidanlumab Tesirine (ADCT-301) in participants with relapsed or refractory Hodgkin Lymphoma (HL).

开始日期2019-09-13

申办/合作机构

ADC Therapeutics SA

NCT03621982

/ Terminated临床1期

A Phase 1b, Open-label, Dose-escalation and Dose-expansion Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of Camidanlumab Tesirine (ADCT-301) as Monotherapy or in Combination in Patients With Selected Advanced Solid Tumors

This study evaluates ADCT-301 in patients with Selected Advanced Solid Tumors. Patients will participate in a Treatment Period with 3-week cycles and a Follow-up Period every 12 weeks for up to 1 year after treatment discontinuation.

开始日期2018-11-09

申办/合作机构

ADC Therapeutics SA

100 项与卡米达卢单抗特西林相关的临床结果

登录后查看更多信息

100 项与卡米达卢单抗特西林相关的转化医学

登录后查看更多信息

100 项与卡米达卢单抗特西林相关的专利（医药）

登录后查看更多信息

项与卡米达卢单抗特西林相关的文献（医药）

2024-11-01·BRITISH JOURNAL OF HAEMATOLOGY

Targeting CD25+ lymphoma cells with the antibody–drug conjugate camidanlumab tesirine as a single agent or in combination with targeted agents

Article

作者: Bertoni, Francesco ; Van Berkel, Patrick H. ; Scalise, Lorenzo ; Spriano, Filippo ; Zammarchi, Francesca ; Zucca, Emanuele ; Cacciapuoti, Maria Teresa ; Golino, Gaetanina ; Inghirami, Giorgio ; Gaudio, Eugenio ; Cascione, Luciano ; Tarantelli, Chiara ; Stathis, Anastasios

Summary:

Camidanlumab tesirine (ADCT‐301) is a CD25‐specific antibody‐drug conjugate (ADC) employing SG3199, a highly cytotoxic DNA minor groove cross‐linking pyrrolobenzodiazepine dimer. The ADC has shown early clinical antitumour activity in various cancers, including B‐ and T‐cell lymphomas. We assessed its preclinical activity as a single agent in 57 lymphoma cell lines and in combination with selected drugs in T‐cell lymphoma‐derived cell lines. Cells were exposed to increasing concentrations of the ADC or SG3199 for 96 h, followed by an MTT proliferation assay. CD25 expression was measured at cell surface and RNA levels. Experiments with PDX‐derived cell lines were used for validation studies. Camidanlumab tesirine presented more potent single agent in vitro cytotoxic activity in T‐ than B‐cell lymphomas. In vitro activity was correlated with CD25 cell surface and RNA expression. In vitro activity was correlated with CD25 cell surface and RNA expression. When camidanlumab tesirine‐containing combinations were evaluated in four T‐cell lymphoma models, the most active partners were everolimus, copanlisib, venetoclax, vorinostat, and pralatrexate, followed by bortezomib, romidepsin, bendamustine, and 5‐azacytidine. The strong camidanlumab tesirine single‐agent anti‐lymphoma activity and the in vitro synergisms with targeted agents identify potential combination partners for future clinical studies.

2023-12-08·Hematology. American Society of Hematology. Education Program

The optimal management of relapsed and refractory Hodgkin lymphoma: post–brentuximab and checkpoint inhibitor failure

Article

作者: Beaven, Anne W. ; Grover, Natalie S. ; Thakkar, Astha ; Dittus, Christopher

Abstract:

The treatment landscape of classical Hodgkin lymphoma has changed dramatically over the past decade. Relapsed and refractory mainstay therapeutics such as brentuximab vedotin (BV) and checkpoint inhibitors (CPIs) are being moved to earlier lines of therapy. However, the treatment of patients who progress after BV and CPI remains a challenge. Allogeneic stem cell transplantation still plays an important role in this patient population as the only current treatment approach with curative potential. Unfortunately, not all patients are transplant candidates, and many will still relapse afterward. Cytotoxic chemotherapy and radiation may be used for symptom palliation or as a bridge to transplant. Targeted therapies, including the antibody drug conjugate, camidanlumab tesirine, and transcriptional agents such mammalian target of rapamycin and histone deacetylase inhibitors have shown some potential in patients with refractory disease. In addition, combination therapies with CPIs and novel agents may help overcome resistance to therapy. Clinical trials with cellular therapies, including chimeric antigen receptor T cells targeting CD30 and allogeneic natural killer cells combined with AFM13, a CD30/CD16a-bispecific antibody, have shown promising results. The availability of more therapeutic options for this patient population is eagerly awaited.

2023-07-01·Journal of the European Academy of Dermatology and Venereology : JEADV

Development of recalcitrant cutaneous eruptions in patients with relapsed/refractory Hodgkin's lymphoma undergoing treatment with camidanlumab tesirine

Letter

作者: Jaglowski, Samantha ; Chung, Catherine ; Dulmage, Brittany ; Maddocks, Kami ; Bond, David ; Kaffenberger, Benjamin H. ; Himed, Sonia

In a study of a surrogate of camidanlumab tesirine in murine solid tumors, depletion of intratumoral regulatory T cells was accompanied by increased activation and proliferation of CD8+ effector T cells in the intratumoral microenvironment resulting in an increase in T-effector to regulatory T-cell ratio.In the setting of relapsed/refractory classical Hodgkin Lymphoma (r/r-HL), only 50% of patients achieve remission with standard of care of salvage therapy and autologous stem cell transplantation.We have observed a long-standing characteristic corticosteroid-recalcitrant dermatitis associated with Camidanlumab tesirine.

项与卡米达卢单抗特西林相关的新闻（医药）

2026-03-20

·allsci.com

BMS’s Opdivo becomes first PD-1 for front-line advanced Hodgkin lymphoma

The US FDA issued an approval notice for Opdivo (nivolumab) in combination with doxorubicin, vinblastine, and dacarbazine (AVD) for adult and pediatric patients aged 12 years and older with previously untreated, Stage III or IV classical Hodgkin lymphoma (cHL). The approval, granted to Bristol Myers Squibb (BMS), makes nivolumab the first PD-1 checkpoint inhibitor authorized for frontline use in advanced cHL, a disease that affects approximately 8,500 to 9,000 people annually in the United States. Concurrently, the FDA converted nivolumab’s prior accelerated approvals from 2016 and 2017 for relapsed or refractory cHL to traditional approvals. The application received priority review and orphan drug designation, and was reviewed under Project Orbis in collaboration with regulatory agencies in Israel, Australia, Canada, and Switzerland. The approval covers nivolumab at 240 mg for adults and pediatric patients weighing 40 kg or more, or 3 mg/kg for those under 40 kg, administered intravenously on Days 1 and 15 of each 28-day cycle for up to six cycles in combination with AVD. Primary G-CSF prophylaxis is recommended starting in Cycle 1. The traditional approval conversion applies to two previously accelerated indications in adults with relapsed or refractory disease: after autologous hematopoietic stem cell transplantation and brentuximab vedotin, and after three or more lines of systemic therapy including autologous transplantation. The approval rests on results from SWOG S1826 (Study CA209-8UT), a randomized, open-label, multicenter Phase III trial that enrolled 994 patients aged 12 years and older with previously untreated Stage III or IV classical Hodgkin lymphoma. Patients were randomized 1:1 to receive either nivolumab plus AVD or brentuximab vedotin plus AVD for six cycles. The primary endpoint was investigator-assessed progression-free survival. The nivolumab arm demonstrated a hazard ratio of 0.42 (95% CI: 0.27–0.67; p<0.0001), corresponding to a 58% reduction in the risk of progression or death. Median progression-free survival was not reached in either arm after a median follow-up of 13.7 months. At a median follow-up of 36.7 months, deaths occurred in 1.8% of patients receiving nivolumab plus AVD compared with 3.4% in the brentuximab vedotin arm. Serious adverse reactions occurred in 39% of patients in the nivolumab arm, with immune-mediated adverse reactions reported in 9% of patients, of which 2.7% were Grade 3 or 4. This approval alters the treatment landscape for advanced cHL, where brentuximab vedotin (Adcetris, Seagen/Pfizer) combined with AVD has been an important frontline standard, particularly in advanced-stage disease, since its approval in 2018 based on the ECHELON-1 trial. The SWOG S1826 trial was designed as a direct head-to-head comparison between the two regimens, and the magnitude of the progression-free survival difference was substantial. For BMS, the approval extends Opdivo’s reach into a new line of therapy for a disease where it previously held indications only in the relapsed or refractory setting. Classical Hodgkin lymphoma disproportionately affects adolescents and young adults, a population for whom long-term treatment toxicity is a persistent concern. Both the nivolumab and brentuximab vedotin combination regimens use AVD rather than the older ABVD backbone, eliminating bleomycin and its associated pulmonary toxicity. The field continues to evolve, with investigational approaches including CD30-directed CAR-T cell therapies, dual checkpoint blockade, and anti-CD25 antibody-drug conjugates such as camidanlumab tesirine (ADC Therapeutics) in development for relapsed or refractory disease. An open question is how to manage patients who relapse after receiving PD-1 inhibitor-based frontline therapy, a clinical scenario that will become more common as this regimen enters routine practice. Your email address will not be published. Required fields are marked * Comment * Name * Email * Website

上市批准临床3期临床结果孤儿药加速审批

2026-02-23

·PRNewswire

ADC Therapeutics Announces Amended HealthCare Royalty Financing Agreement

LAUSANNE, Switzerland, Feb. 23, 2026 /PRNewswire/ -- ADC Therapeutics SA (NYSE: ADCT), a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), today announced that it has entered into an amendment to its royalty purchase agreement with entities managed by HealthCare Royalty. Based on confidence in the long-term outlook for ZYNLONTA®, ADC Therapeutics negotiated mutually beneficial updated terms with HealthCare Royalty, offering greater strategic flexibility to the Company. The new agreement reduces the change of control payment from $750 million to $150 million through the end of 2027, and to $200 million thereafter. In the event of a change of control, HealthCare Royalty will continue to receive royalties on sales by the acquirer until the original royalty cap is reached. In return, HealthCare Royalty has been granted warrants to purchase approximately 9.8 million common shares, with an exercise price of $3.81 per share. These warrants are exercisable until December 31, 2030, and are subject to a lock-up through the end of 2027. "We are pleased by this meaningful amendment to the terms of our partnership with HealthCare Royalty, based on our shared conviction in ZYNLONTA's potential, as it enables greater strategic flexibility for our Company," said Ameet Mallik, Chief Executive Officer of ADC Therapeutics. "With a robust and growing body of evidence, including multiple expected data readouts this year across our clinical programs supporting the best-in-class potential of ZYNLONTA, we anticipate meaningful growth beginning in 2027. Assuming compendia inclusion and regulatory approval, potential peak revenue in the US could reach $600 million to $1 billion annually." "This updated agreement is a result of our belief in the long-term upside of ZYNLONTA," said Clarke Futch, Chairman and Chief Executive Officer of HealthCare Royalty. "The combination of existing and upcoming ZYNLONTA data in diffuse large B-cell lymphoma and other indolent lymphomas has enhanced our confidence in the Company's focused portfolio, which we believe will unlock significant value." HealthCare Royalty had previously provided $300 million of funding under the original agreement and, conditional upon the occurrence of a change of control event, ADC Therapeutics was obligated to buy out the remaining royalty obligations for $750 million (or $675 million if HealthCare Royalty receives specified minimum royalty payments before March 31, 2029), less the amount of royalties previously paid to HealthCare Royalty. Under the amendment: Upon the occurrence of a change of control event, ADC Therapeutics is obligated to pay HealthCare Royalty $150 million (if the change of control event occurs on or before December 31, 2027) or $200 million (if the change of control event occurs on or after January 1, 2028), which amount is not reduced by the amount of royalties previously paid to HealthCare Royalty. Following any such change of control, the royalty obligations under the royalty purchase agreement will continue to be paid up to the original royalty cap, unless ADC Therapeutics (or its successor in interest) buys out the remaining royalty obligations by paying HealthCare Royalty $525 million (if the buyout occurs on or prior to December 31, 2029) or $750 million (if the buyout occurs on or after January 1, 2030), less the amount of royalties previously paid to HealthCare Royalty and the change of control payment described above. About ZYNLONTA® ZYNLONTA® is a CD19-directed antibody drug conjugate (ADC). Once bound to a CD19-expressing cell, ZYNLONTA is internalized by the cell, where enzymes release a pyrrolobenzodiazepine (PBD) payload. The potent payload binds to DNA minor groove with little distortion, remaining less visible to DNA repair mechanisms. This ultimately results in cell cycle arrest and tumor cell death. The U.S. Food and Drug Administration (FDA) and the European Medicines Agency (EMA) have approved ZYNLONTA (loncastuximab tesirine-lpyl) for the treatment of adult patients with relapsed or refractory (r/r) large B-cell lymphoma after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from low-grade lymphoma and also high-grade B-cell lymphoma. The trial included a broad spectrum of heavily pre-treated patients (median three prior lines of therapy) with difficult-to-treat disease, including patients who did not respond to first-line therapy, patients refractory to all prior lines of therapy, patients with double/triple hit genetics and patients who had stem cell transplant and CAR-T therapy prior to their treatment with ZYNLONTA. This indication is approved by the FDA under accelerated approval and in the European Union under conditional approval based on overall response rate and continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Please see full prescribing information including important safety information about ZYNLONTA at . About ADC Therapeutics ADC Therapeutics (NYSE: ADCT) is a commercial-stage global leader and pioneer in the field of antibody drug conjugates (ADCs), transforming treatment for patients through our focused portfolio with ZYNLONTA (loncastuximab tesirine-lpyl). ADC Therapeutics' CD19-directed ADC ZYNLONTA received accelerated approval by the FDA and conditional approval from the European Commission for the treatment of relapsed or refractory diffuse large B-cell lymphoma after two or more lines of systemic therapy. ZYNLONTA is also in development in combination with other agents and in earlier lines of therapy. Headquartered in Lausanne (Biopôle), Switzerland, with operations in New Jersey, ADC Therapeutics is focused on driving innovation in ADC development with specialized capabilities from clinical to manufacturing and commercialization. Learn more at adctherapeutics.com and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. In some cases you can identify forward-looking statements by terminology such as "may", "will", "should", "would", "expect", "intend", "plan", "anticipate", "believe", "estimate", "predict", "potential", "seem", "seek", "future", "continue", or "appear" or the negative of these terms or similar expressions, although not all forward-looking statements contain these identifying words. Forward-looking statements are subject to certain risks and uncertainties that can cause actual results to differ materially from those described. Factors that may cause such differences include, but are not limited to: whether future LOTIS-7 clinical trial results will be consistent with or different from the LOTIS-7 data presented by the Company on December 3, 2025, the timing, publication and outcome of the full LOTIS-7 trial, compendia inclusion and regulatory strategy and the commercial opportunity; the timing of the PFS events and topline data release for LOTIS-5 and the results of the trial, the timing for the sBLA submission and full FDA approval; the Company's ability to grow ZYNLONTA® revenue in the United States and potential peak revenue; the ability of our partners to commercialize ZYNLONTA® in foreign markets, the timing and amount of future revenue and payments to us from such partnerships and their ability to obtain regulatory approval for ZYNLONTA® in foreign jurisdictions; the timing and results of the Company's clinical trials; the timing, publication and results of investigator-initiated trials including those studying FL and MZL and the potential regulatory and/or compendia strategy and the future opportunity; the timing and outcome of regulatory submissions for the Company's products or product candidates; actions by the FDA or foreign regulatory authorities; projected revenue and expenses; the Company's indebtedness, including HealthCare Royalty Management and Blue Owl and Oaktree facilities, and the restrictions imposed on the Company's activities by such indebtedness, the ability to comply with the terms of the various agreements and repay such indebtedness and the significant cash required to service such indebtedness; and the Company's ability to obtain financial and other resources for its research, development, clinical, and commercial activities; and the uncertainties of international trade policies, including tariffs, sanctions, trade barriers and most favored nation drug pricing and the potential impact they may have on our business, financial condition, and results of operations. Additional information concerning these and other factors that may cause actual results to differ materially from those anticipated in the forward-looking statements is contained in the "Risk Factors" section of the Company's Annual Report on Form 10-K and in the Company's other periodic and current reports and filings with the U.S. Securities and Exchange Commission. These statements involve known and unknown risks, uncertainties and other factors that may cause actual results, performance, achievements or prospects to be materially different from any future results, performance, achievements or prospects expressed in or implied by such forward-looking statements. The Company cautions investors not to place undue reliance on the forward-looking statements contained in this document. CONTACTS: Investors and Media Nicole Riley ADC Therapeutics [email protected] +1 862-926-9040 SOURCE ADC Therapeutics SA 21% more press release views with Request a Demo

上市批准抗体药物偶联物加速审批免疫疗法细胞疗法

2025-11-04

·医药速览

普华资本竺宝琳：从ADC看各类偶联药物的发展机会| 普华慧

竺宝琳普华资本投资副总裁除了比较成熟的ADC、FDC、RDC外，随着偶联技术和对分子类型认知的提升，有望实现突破性发展的领域有蛋白降解偶联药物和抗体-核苷偶联药物等。当然除了科学性考量外还需要考虑市场情况和竞争优势，但下一代“ADC”仍然有很大的机会出现。文丨竺宝琳 2023年3月，辉瑞以430亿美元并购Seagen；4月初，映恩生物成为继荣昌生物、科伦药业之后又一个获得超亿美元首付款的国内ADC创新药企。回顾过去几年，ADC在全球市场交易持续火热，该领域何以吸引巨头重金下场，除了ADC自身各组分迭代优化外，下一个“ADC”在何方？ 01. ADC交易回顾 ADC的交易数量和交易方式：自2018年以来，ADC相关资产的交易量增长了三倍多，授权模式和共同开发模式占比最高。 ADC不同临床阶段的交易数量： ADC交易经常在产品开发生命周期的早期达成。可见人们对早期的技术/资产有明显的兴趣，特别是在发现阶段，涉及单抗选择、优化链接子和毒素选取等方面。 ADC与其他不同分子形式平均交易首付款和里程碑付款对比：虽然ADC的交易频率低于某些分子形式，但ADC获得的交易价值最高。平均而言，所有阶段的首付款为8.51亿美元 (基于42项已披露的交易)，其中5项交易的首付款为10亿美元。在评估总交易金额中位值时，ADC的总体价值为8.48亿美元，比多/双特异性抗体的中位值5.12亿美元高出3亿美元。 ADC不同临床阶段的交易规模： ADC的交易版图中最引人注目的是各个开发阶段的整体交易价值。虽然从临床前到3期临床的整体交易价值也在持续增加（从临床前的约25亿美元到3期临床的约40亿美元），但首付款显著增加（从临床前的5200万美元到I期临床的5.2亿美元），这表明了通过临床数据实现的成药性风险消除价值。 02. 为何是ADC? ADC 药物自开发至今已有接近 100 多年历史，其首次真正尝试源于 1958 年，Mathe 将抗鼠白细胞免疫球蛋白与甲氨蝶呤偶联用于白血病的治疗。但这次尝试以失败告终，直到 2000 年第一款 ADC 药物 -吉妥珠单抗才正式上市；2011 年第二款 ADC 药物维布妥昔单抗上市，自此之后的 11 年接连上市了 10多款药物。总体来说，ADC 药物从 2011 年开始才真正意义上进入了发展的快车道。不同于大多数前沿疗法叫好不叫座，近5年来ADC凭借颠覆性的临床疗效及广覆盖的适应应用，正在释放巨大商业价值。DS-8201在2019年底以末线疗法上市以来，不断往前线和Her2低表达攻克，商业上气势如虹，2022年全球销售额12.6亿美元，《Nature》预计其 2026年销售额将达到62亿美元。 (一）结构决定性质抗体偶联药物（ADC，Antibody Drug Conjugate）由三部份组成，分别是能够对癌细胞靶向的单克隆抗体、高生物活性的小分子药物以及能够将单抗和小分子药物连接的连接子。抗体与癌细胞表面抗原结合后介导ADC通过内吞作用进入细胞，经内体运输进入溶酶体，在溶酶体中ADC的连接子或抗体部分降解，并释放细胞毒性小分子药物杀死肿瘤细胞。 ADC药物研发核心在于抗体、连接子、小分子毒素、偶联技术等四大基本要素。 1.1抗体方面涉及靶标选择和抗体类型选择靶标（Target）选择：理想的靶点可以获得更低的非特异性毒副作用以及更好的治疗指数。通常可选择的靶抗原有在肿瘤组织表达的特异性抗原（TSA）和在肿瘤组织中高表达而在正常组织中低表达的肿瘤相关抗原（TAA）。除了特异性表达要求外，这些这些靶点还需要有介导内吞作用，从而实现小分子药物在胞内起效。研究发现，ADC 活性与细胞表面的抗原数量相关，至少需要 10 4的表面抗原才能确保致死剂量的细胞毒性药物被递送到细胞内部实现ADC药物的起效，但DS-8201在her2低表达适应症的临床成功也给未来靶点选择拓宽了思路。 ADC有丰富的靶点选择空间： − 已成药的抗体靶点（如Her2）； − 靶部位高表达可内吞且机理较清晰的尚未成药靶点（如叶酸受体-α/FR-α）； − 机理尚未完全验证的未成药靶点 15款上市的ADC药物对应11个靶点，分别为CD33、CD30、HER2、CD22、CD79b、Nectin-4、BCMA、EGFR、CD19、TissueFactor和FRα。据药智网和医药魔方数据库统计在研的425款ADC药物中较为热门的靶点包括HER2、EGFR、CLDN18.2、TROP2、c-Met、CD19、PSMA、Muc1、BCMA和PDL1，大多数为验证成熟的靶点。更进一步待验证的ADC靶点有：注：由义翘神州公开资料整理抗体（Antibody）选择：抗体可变区选择和靶点高度相关，本身要求其满足高特异性、强靶点结合能力；恒定区选择要求低免疫原性、低交叉反应活性，以达到肿瘤细胞对ADC药物更高效的摄入和ADC药物在血清中更长的半衰期。 − ADC中抗体来源选择经历了大致四个阶段，即鼠源、嵌合体、人源化以及全人源抗体。由于鼠源、嵌合体抗体在不同程度上受到高免疫排异、低效性以及较短的循环半衰期影响，随着抗体和基因工程技术的发展，人源化以及全人源抗体成为ADC药物设计中的第一选择，现在绝大多数临床和临床前研究都采用后两种抗体。 − 除了抗体来源外，人的抗体还有多种亚型，其中IgG1在血清中丰富最高，也能够较好地平衡长半衰期和强免疫激活的关系，是被研究和采用最多的ADC抗体。除IgG1之外，IgG4由于较低的免疫激活效应也经常被采用在一些对免疫原性反应要求较高的ADC药物设计中。IgG1和IgG4都具有12个链内二硫键和4个链间二硫键，其中链间二硫键具有较高反应活性常被作为连接子反应位点。但是由于IgG4具有较高的Fab段交换性质会引起脱靶效应，所以在ADC药物设计在使用IgG4抗体时还需采取S228P 位点变异的策略来降低Fab段交换。 − 此外由于抗体本身具有某些信号作用，如抗体依赖性细胞毒性（ADCC）、抗体依赖的细胞吞噬（ADCP）和补体依赖性细胞毒性（CDC）也应被慎重考虑。ADCC和ADCP会介导免疫系统参与杀伤肿瘤细胞过程，对最终ADC的治疗效果产生影响，因此在设计ADC药物时必须对抗体的ADCC、ADCP效应有充分的研究。 1.2小分子毒素（Payloads）的选择：毒素分子是 ADC 药物研发成功的关键因素，直接决定对靶细胞的杀伤效果。早期ADC药物研究一般选择包括阿霉素在内的传统小分子化疗药物，但是注射入体内的抗体仅仅只有很小的一部分聚集在实体瘤组织中，且单个抗体偶联小分子药物数量有限，导致那些半数抑制浓度（IC50）在微摩尔级别的小分子药物并不能达到很好的治疗效果。现在在选择小分子药物时往往要求小分子药物IC50值低至纳摩尔级别乃至皮摩尔级别。这些小分子药物主要包括两类，即微管蛋白抑制剂和DNA 损伤剂。另外，毒性分子必须具有可偶联的合适的功能基团，强大的细胞毒性，具有疏水性，且在生理条件下要非常稳定。除需要较低的IC50值以外，通常还要求小分子药物有以下属性：1)在与抗体偶联后不易引起ADC药物发生聚集以保证在体内拥有较长的循环时间；2)本身以及构成ADC药物后较低的免疫原性；3)在水溶液、血液中足够稳定且具有合适的反应位点；4）通过连接子与抗体偶联，偶联后仍然能够保证其生物活性；5）可以通过相对经济的过程合成。 1.3连接子（Linker）的选择：尽管根据肿瘤细胞的类型选择特异性抗体和 payloads 很重要，但就药代动力学，药理学和治疗窗口来说，连接子能够对最终获得ADC药物的毒性、稳定性、特异性等性质产生巨大影响，通过选择合适的 linker 来约束抗体和 payloads 是成功构建 ADC 的关键。理想的 linker 必须满足以下条件：1）linker 需要在血液循环系统中稳定存在，当定位到肿瘤细胞内或附近时能快速释放活性 payloads，linker 的不稳定性会导致 payloads 的过早释放，造成对正常组织细胞的损伤；2）ADC 一旦被内化到靶肿瘤组织中，linker 需要具有被快速裂解并释放毒性分子的能力；3）亲疏水性也是 linker 考虑的一个重要特性，疏水性连接基团和疏水性 payloads 通常会导致 ADC 小分子的聚集，从而引起免疫原性。连接子大体上可以分为第一代ADC药物采用的不可裂解型和第二、三代ADC药物采用较多的可裂解型。不可裂解型：不可裂解型连接子主要包括马来酰型以及含硫醇己酰胺型连接子，通过形成酰胺键以及硫醚键将小分子药物与抗体偶联。不可裂解型连接子能够保证ADC药物在体内循环中保持较高的稳定性，经抗体-抗原介导进入细胞后通过内体运输进入溶酶体，然后抗体在溶酶体中各种生物酶的作用下裂解释放小分子药物进而产生细胞毒性。但通常采用不可裂解型连接子的ADC药物一般针对性靶向具有高抗原表达肿瘤细胞而很少影响周边低抗原表达的肿瘤细胞，这是由于ADC药物在溶酶体中酶解后的小分子药物通常带有具有电荷的氨基酸残留物，这些带电氨基酸-小分子复合物不能够进出细胞膜进而通过旁观者效应杀伤周围肿瘤细胞。可裂解型：可裂解型连接子利用其在血液系统和肿瘤细胞的环境差异，主要分为pH敏感型（腙类、碳酸酯类）、酶敏感型（多肽类、β-葡萄糖醛酸苷类）以及可还原型（二硫键），分别利用进入肿瘤组织酸性内体（PH=5.0-6.0）或溶酶体（PH=4.8）中较低的pH值、肿瘤细胞内蛋白酶、肿瘤细胞内较高的还原性来裂解连接子。采用这一类型连接子的ADC药物在通过抗体靶向定位肿瘤细胞，在肿瘤区域富集并利用肿瘤细胞特殊的微环境的刺激使连接子断裂释放小分子药物，从而产生抑制细胞增殖和杀伤细胞的效果。与不可裂解型连接子相比对肿瘤细胞内吞的依赖性较低，有利于ADC的旁杀伤效应。可见，选择何种类型的 linker 与靶标选择密切相关。在具有可切割 linker 的 ADC 药物中，靶标为 B 细胞抗原(CD19，CD20，CD21，CD22，CD79B，CD180) 的，被证实在体内非常有效。相反，带有不可切割 linker 的 ADC 药物中，被证实在体内内吞并快速转运到溶酶体的靶标如CD22，CD79b有效。 1.4偶联技术偶联方法可分为化学偶联和酶偶联，也可分为定点偶联和非定点偶联。化学偶联包括：赖氨酸酰胺偶联、半胱氨酸偶联、引入非天然氨基酸偶联。赖氨酸酰胺偶联：赖氨酸残基上的氨基可以与含有活性羧酸酯的连接子以酰胺键连接，进一步实现与药物偶联。由于抗体表面赖氨酸残基数量众多，该方法得到的ADC中将包含不同DAR和多种偶联部位的偶联物，优化后得到的最佳均值DAR为3.5-4，实际分布为0-7，均一性差。同时，一些赖氨酸残基在抗原抗体相互作用中很重要，该方法会降低抗体的亲和性。半胱氨酸偶联包括： 1）传统半胱氨酸偶联：一般情况下，抗体中半胱氨酸残基链间和链内都有巯基，以二硫键形式存在，链间的二硫键对抗体性质基本没有影响，可以采用温和的还原方法使其断裂，得到游离巯基。在IgG1中，有4个链间二硫键和12个链内二硫键，可以将链间二硫键选择还原为2、4、6或8个二硫键，进一步进行偶联。由于可偶联部位少，该方法优于赖氨酸酰胺偶联，但均一性仍有待提升； 2）工程化突变半胱氨酸偶联（Thiomab技术）：通过定点诱变，在单抗中人工引入半胱氨酸残基用于偶联。这样得到的ADC的DAR均值为1.9，抗体均一性大于90%，体内外都有活性； 3）半胱氨酸二硫键重架桥偶联：利用二溴马来酰亚胺等试剂，可以在还原后的链间巯基之间形成重架桥，实现定点偶联，得到的DAR主要为4； 4）芳基钯高选择性偶联：利用芳基钯进行高选择性偶联，得到的DAR主要为4.4。该方法不需要连接子，产物对酸、碱、氧化稳定，但是用到钯催化剂，需要考虑毒性、价格、钯残留等问题。第一种方法为非定点偶联，后三种方法为定点偶联。插入非天然氨基酸偶联：引入非天然氨基酸，利用其上的特征官能团进行偶联，方法包括： 1）通过一种特殊的密码子-tRNA合成酶可以在蛋白质中引入含有羰基的p-乙酰基苯丙胺残基，利用该羰基与烷氧胺生成肟，进一步与药物偶联； 2）引入含有叠氮基团的非天然氨基酸残基，如p-叠氮甲基苯丙胺等可以与炔基通过叠氮-炔环化反应连接，通过改变炔的结构，该反应在铜催化条件存在与否的情况下都可以进行。插入非天然氨基酸偶联属于定点偶联技术，得到的ADC具有较好的均一性，但该方法需要特殊的技术，且这些非天然氨基酸的免疫原性未知，需要考虑安全性。酶偶联包括：转肽酶催化转肽反应偶联、细菌谷氨酰胺转氨酶催化转氨反应偶联、N-聚糖工程偶联、甲酰甘氨酸生成酶催化反应偶联等。 (二）技术迭代助力临床优效从ADC药物发展至今，从技术迭代的角度看，可以分为三代。 2.1 同靶点HER2-ADC的对比 ADC的三要素抗体、连接子、载荷，每一项都是影响最终药物安全性和有效性的关键。无论是罗氏的Kadcyla（T-DM1）、第一三共的Enhertu （DS-8201）还是荣昌生物的RC48，都在各自的系统中，做到了三要素的平衡。 Kadcyla 作为先行者，开拓了ADC治疗实体瘤领域。而Enhertu和RC48，作为后来者不仅是致敬T-DM1，也通过自身技术的积累和更新，升级HER-2 ADC，挑战T-DM1的治疗效果。靶点选择： HER2在肿瘤细胞的表达量较正常细胞有100倍以上的差异，且HER2已经有成熟抗体药物，使其成为ADC治疗实体瘤一个较为理想的靶点。三家药企都选择了HER2作为ADC药物开发的靶点。这样在验证ADC平台时可避免生物学机理不清晰的挑战。抗体： T-DM1凭借曲妥珠单抗强内吞活性，将DM1递送至细胞内发挥肿瘤细胞的杀伤作用。DS-8201，与T-DM1同样使用了曲妥珠单抗，其亮点是独特的linker-payload系统大大增强了其药效。RC48, 使用了自主研发新型抗体-Disitamab，与曲妥珠单抗具有不同HER2表位，对HER2具有高度选择性。Disitamab具有更高的亲和力，EC50 为6.4pM, 曲妥珠单抗的EC50为20.1pM。 Linker： T-DM1使用MCC的不可裂解 linker。而DS-8201和RC48 则采用GGFG 和VC的可裂解linker，可裂解 linker有利于ADC的旁杀伤效应。减小ADC药物的疏水性有利于减少ADC体内清除，增强ADC药效。DAR值也直接关联着ADC的药效。而增加DAR值和减少疏水性存在一定的矛盾，因此，linker的亲水性就显得十分重要。DS-8201通过优化筛选上百种linker，建立起自其独特的linker-payload系统，使得DAR值可以高达8，且仍然保持较好的亲水性。独有的linker技术贡献了第一三共ADC成功的关键。载荷：由于肿瘤细胞表面上抗原的数量有限（平均每个细胞表面约 5,000 至 106的抗原），而且大多数临床阶段的 ADC 药物平均 DAR 为 3.5 至 4，所以 ADC 药物传递到肿瘤细胞内的很少。这也被认为 ADC 中偶联常规细胞毒性药物如甲氨蝶呤、紫杉醇和蒽环类抗生素等临床失败的主要原因之一。T-DM1采用了低通透性DM1毒素，而随着科学研究深入，第一三共研发了高通透性的DXd毒素，荣昌生物使用了较好的MMAE毒素，两者都比DM1 具有更高的膜通透性。毒素释放后，可穿透相邻细胞产生旁杀效应。从荣昌招股书中动物实验发现，3.3mg/kg RC48对靶细胞的旁观者效应明显强于10mg/kg T-DM1。此外，有研究表明不可裂解linker和细胞膜低通透性的DM1毒素，导致T-DM1在溶酶体中的大量积累，使得长时间的药物暴露，是造成T-DM1耐药的一个重要原因。 2.2 ADC成功的必然性和偶然性必然性：生物学确定性。肿瘤治疗的终极目标是选择性杀死肿瘤细胞而不损伤正常细胞。化疗药物这么多年之所以一直能够占据肿瘤治疗的一线疗法，正式因为其确切几乎无差别的杀伤效果，但也伴随着耐药和显著副作用问题。ADC药物从科学性上最简单的逻辑就是将化疗药物或比化疗药物毒性更大的毒素靶向递送到肿瘤细胞，没有生物学和科学性疑问。如果能够精准递送，则必然成功。偶然性：技术创新性。由于ADC涉及抗体、毒素、连接子、偶联方式等多个关键因素，哪一个团队能够在某一方面形成突破或迭代进化有很大的不确定。随着抗体技术日渐成熟，DS-8201通过对毒素、连接子的筛选，创新偶联方式，形成了对Her2靶点的重大突破。但其也仍面临间质性肺炎发生率较高的问题，未来还有新的ADC产品有机会在药物连接设计，甚至抗体全新靶点选择上实现新的迭代。 03. 下一个"ADC"? 跨国药企纷纷重金押注ADC赛道，势头不亚于早些年的PD-1，过去几年全球科学家也在寻找下一个PD-1，但是肿瘤免疫治疗领域的TIGIT、TGFβ、偏向性IL-2纷纷折戟。那有下一个“ADC”么？对比肿瘤免疫治疗（IO）赛道和ADC，从生物学确定性和技术创新看有很大的不同。IO赛道的创新药研发可能更侧重基础生物学的突破，新靶点、新机理、新通路，但是ADC领域目前看到主要突破在分子设计和偶联技术，其构成有确定机理的靶点以及确定起效的载荷，相比IO在科学性上的风险更小，对技术可实现性要求更高。从ADC的结构出发探索可成药的分子结构，就配体、连接子和载荷方向做了可能的延伸：除了抗体+linker+小分子毒素的ADC设计外，通过排列组合，我们还可以看到：抗体片段偶联药物（FDC）、多肽偶联药物（PDC）、小分子偶联药物（SMDC）、核素偶联药物（RDC）、抗体免疫刺激偶联药物（ISAC）、抗体降解偶联药物（ADeC）、抗体细胞偶联药物（ACC）、病毒样药物偶联物（VDC）、抗体寡核苷酸偶联物（AOC）、抗体生物聚合物偶联物（ABC）等。从配体类型分类：抗体片段偶联药物（FDC）和ADC的主要差别在于将全长的抗体换成抗体片段，主要依托于新的抗体工程技术发展，更小的抗体结构在肿瘤渗透上可能也有更好的疗效，同时由于结构缩小连接位点的选择也可能更为受限，药物代谢上可能与全长抗体也有区别。多肽偶联药物（Peptide-Drug Conjugates，PDC）主要是将靶头从ADC的抗体换成归巢肽，相比于目前ADC 药物，PDC 药物具有分子量小、肿瘤穿透性强、免疫原性低、利用固相合成法可大规模合成、生产成本较低、相对较好的药代动力学等特点。但目前多肽药物主要为内源性多肽的衍生物，如奥曲肽、GLP-1、胰岛素等，如何开发高亲和力的靶向多肽可能比ADC中的抗体要做更多的研究。小分子偶联药物（Small molecule-drug conjugates，SMDC）采取小分子定向，小分子之间的定点偶联技术可以实现相对准确的药物抗体比（DAR）。SMDC由纯小分子构成容易控制成本；理论上不会具有免疫原性，安全性控制更容易实现；分子量相较于ADC要低很多，从而在实体瘤中能够具有更好的细胞通透性以及更好的体外和体内稳定性。同时，也要考虑到SMDC的小分子配体选择并没有ADC抗体那样直接，筛选合适配体的难度较大。此外分子量小有优势也需要考虑半衰期和口服给药可实现性。从广义上看蛋白降解靶向联合体（PROTAC）也属于SMDC，通过小分子实现靶向将E3连接酶带到靶标实现目标分子的降解。但是PROTAC要求linker是不可断裂的，SMDC的linker是可裂解的。从可裂解的角度看，小分子前药设计也可以归入SMDC，但前药可能不一定要求有可靶向性的配体。同理核酸适配体偶联物（ApDC）、DNA嵌合体偶联物（如DNA嵌合体靶向水解，DENTAC）、病毒样颗粒偶联物（VDC）等主要将抗体变换为全新的配体成分。从筛选难度上看，也许抗体是最容易获得和做靶点差异化选择的配体。从载荷类型分类：核素偶联药物（Radionuclide Drug Conjugates，RDC）是利用抗体（Antibody-radionuclide Conjugate，ARC）或小分子（包括多肽，Peptide-radionuclide Conjugate，PRC）介导的靶向定位作用将细胞毒/成像因子（放射性核素放射性同位素，Radionuclide radioisotope）精准定位至靶位置，避免全身暴露的潜在危害。不同之处是，RDC载荷是放射性核素，既可用于诊断也能实现治疗功能；组成上与ADC也略有差异，需要添加螯合毒素的特定官能团结构。代表药物有诺华的镥177氧奥曲肽、177Lu-PSMA-617等。抗体-免疫刺激偶联物（Immune stimulating antibody conjugate，ISAC）和抗体-免疫调节偶联物（Immune modulating antibody conjugate，IMAC）主要是将免疫激动剂或免疫抑制剂连接到抗体上，实现起效成分的靶向释放。这两类有效成分由于其下游效应细胞在体内分布广，如果不能实现有效靶向的话一方面会限制其使用剂量影响疗效，另外一方面会因为全身分布导致靶毒性，故通过抗体实现靶向是比较理想的方式。涉及此类机制的药物主要包括Toll样受体激动剂（TLR）类ISAC药物BDC-1001；STING激动剂ISAC药物XMT-2056，Treg细胞调节IMAC药物ADCT-301等。抗体-降解剂偶联物（Antibody degrader Conjugate，ADeC），它的技术原理是将蛋白降解剂如分子胶或Protac作为payload，兼具抗体的肿瘤特异性和PROTAC分子在催化剂量下对低表达的适用性。代表药物是有Orum Therapeutics开发的ORM-5029。与降解剂相反的药物设计有蛋白稳定剂，DUBTACs也是类似Protac的双功能性分子，它们的一端是与致病蛋白相结合的化合物，通过连接子与能够募集去泛素化酶（DUB）的化合物连接在一起。去泛素化酶能够去除即将被降解的蛋白表面的泛素链，从而防止它们的降解并稳定蛋白水平。2022年这个领域Stablix 、Vicinitas等多家靶蛋白稳定的公司完成早期融资，但尚未看到抗体-稳定剂偶联物（Antibody stabilizer Conjugate，ASC）相关公司。抗体-寡核苷酸偶联物（Antibody oligonucleotide Conjugate，AOC）和抗体-siRNA偶联物（Antibody-siRNA conjugates, AsiRC）的设计是将寡核苷酸或siRNA连接到抗体上。目前RNA类药物面临着肝外靶向性不足的问题，通过抗体实现组织靶向也许是核酸递送的突破方向。相比于ADC携带的毒素，核酸片段的分子量要大很多，其电负性对药物设计也有非常不同的要求。目前代表药物是由Avidity 开发的AOC-1001。Avidity是研发AOC的先驱，该设计结合了单克隆抗体的组织选择性和基于寡核苷酸治疗方法的精确性，从而克服了阻碍寡核苷酸传递的障碍并实现疾病的遗传驱动因素靶向，用于治疗罕见的肌肉疾病和其他严重疾病。率先进入临床的AOC-1001由3部分组成：靶向转铁蛋白受体1的全长单抗、linker、靶向DMPK mRNA的siRNA，适应症为强直性肌营养不良症1型。抗体-生物聚合物偶联物（Antibody-biopolymer Conjugate，ABC）由抗体与生物多聚物通过连接子偶联得到。代表药物是由Kodiak 开发的KSI-301。公司采用800kDa分支状磷酸胆碱多聚物为生物多聚物，该多聚物可以与水结合，与抗体通过不可裂解连接子定点偶联，在抗体外形成一层水屏障，避免其受到非特异性相互作用干扰直达靶点。该平台被设计用于VEGF靶点，提高药物在眼组织内的持续时间，以此提高疗效、减少注射次数，目前正被开发用于治疗视网膜血管疾病和预防糖尿性眼病患者的视力丧失。2022年2月，Kodiak Sciences公布湿性年龄相关黄斑变性KSI-301首个注册临床试验DAZZLE 数据，显示视力矫正较阿柏西普未显示非劣，未达到临床终点；公司分析认为，此次失败的一个重要原因是方案用药间隔过长。抗体-细胞偶联物（Antibody-cell Conjugate，ACC）与CAR-T的作用类似，更偏向于细胞治疗，抗体起到为细胞疗法提供靶向的作用，如CAR-NK，CAR-血小板等。但抗体细胞偶联药物通过化学反应偶联，不需要基因改造，免疫细胞仍保留天然的激活信号系统，抗体仅起到靶向作用。代表药物有Acepodia公司开发的ACE1702。将上述排列组合所得创新平台，根据以下几点考虑，以生物学确定性和技术成熟度为横纵坐标作图： 1.抗体偶联药物（ADC）和抗体片段偶联药物（FDC）相比其他偶联平台相似度最高，随着抗体工程的演进都有比较好的技术成熟度； 2.多肽偶联药物（PDC）、小分子偶联药物（SMDC）和核酸适配体偶联药物（ApDC）由于理想配体筛选难度较抗体更大，故参与企业数量比ADC少，技术成熟度相对较低，同靶点比ADC作出优效的科学性确定性也许要弱一些，但如果找到合适的靶点也有差异化的发展机会； 3.抗体偶联免疫激活剂（ISAC）从技术层面看与ADC有比较相似的设计方法，但目前激活剂单药成药难点比较大，载荷的生物学机理还有很多尚未研究清楚； 4.核素偶联药物（RDC）目前基于多肽和小分子的靶向基础已经有一些药物上市，相对技术成熟度和科学确定性比较高。由于核素管控要求更高，开发企业需要克服的相应技术难点，较ADC的技术普及性稍低； 5.蛋白降解体系的偶联药物有单纯的Protac、以及抗体介导的ADeC和DNA嵌合体介导的DNEtac，这些都依托体内的泛素降解体系，生物学机理已经有相对比较多的研究，但在药物分子结构设计和起效过程中体内三元复合物形成上还有很多技术问题待克服。目前Pretac已有相关分子进入临床研究阶段，其他尚处于临床前； 6.蛋白稳定剂与蛋白降解剂的作用机理相反，抑制泛素降解体系，与体内天然的泛素化系统运作相反，相比降解剂在基础生物学和分子设计上还都有更多要研究的，目前一些企业尚处于临床前阶段； 7.抗体偶联核酸（AOC）解决了目前核酸药物靶向性的核心难题，与ADC相比在连接上会有一些区别和待探索技术。生物学确定性上由于载荷涉及核酸全新序列设计，但这些序列的设计可参考基因组学，类似其他高开发成功率的RNA药物，在生物学成熟度上会有一些挑战但相对可控。 8. 病毒样药物偶联物（VDC）和抗体生物聚合物偶联物（ABC）在药物分子更大，结构更复杂，整体生物学确定性和目前的技术发展都还更早期些。注：1.在坐标中将ADC定位生物学确定性、技术成熟度最高，将新靶点的成熟分子形式（如抗体、小分子）定位生物学确定性最低、技术成熟度最高。2.不同色块对应有较大不同的技术平台，相同色块指相应平台在技术路径或实际应用上有比较好的可替换性。上图中我们可以看到除了比较成熟的ADC、FDC、RDC外，随着偶联技术和对分子类型认知的提升，有望实现突破性发展的领域有蛋白降解偶联药物和抗体-核苷偶联药物等。当然除了科学性考量外还需要考虑市场情况和竞争优势，但下一代“ADC”仍然有很大的机会出现。参考文献： 1.A Payday For Payloads: The Transactional Landscape Of ADCs. 2.Site-selective modification strategies in antibody–drug conjugates. 3.Cleavable linkers in antibody–drug conjugates. 4.Strategies and challenges for the next generation of antibody-drug conjugates. 5. Antibody–Drug Conjugates for Cancer Therapy. 6.Antibody-drug conjugates: recent advances in conjugation and linker chemistries. 7.Characterization of antibody-drug conjugates by mass spectrometry: advances and future trends. 8.Antibody–drug conjugates in solid tumors: a look into novel targets. 9.荣昌生物制药招股书。 10. HER2-ADC的迭代进阶。 11.Antibody–Drug Conjugates: A Comprehensive Review. 12.Antibody–Drug Conjugates (ADCs) for Personalized Treatment of Solid Tumors: A Review. 13.Collaboration on trastuzumab deruxtecan Investor conference call presentation. 14.Avidity、Stablix、Vicinitas、Kodiak、Acepodia等官网. 推文用于传递知识，如因版权等有疑问，请于本文刊发30日内联系医药速览。原创内容未经授权，禁止转载至其他平台。 ©2021 医药速览保留所有权利往期链接 “小小疫苗”养成记 | 医药公司管线盘点人人学懂免疫学| 人人学懂免疫学（语音版）综述文章解读 | 文献略读 | 医学科普|医药前沿笔记 PROTAC技术| 抗体药物| 抗体药物偶联-ADC 核酸疫苗 | CAR技术| 化学生物学温馨提示医药速览公众号目前已经有近12个交流群（好学，有趣且奔波于医药圈人才聚集于此）。进群请扫描上方二维码，备注“姓名/昵称-企业/高校-具体研究领域/专业”，此群仅为科研交流群，非诚勿扰。简单操作即可星标⭐️医药速览，第一时间收到我们的推送 ①点击标题下方“医药速览” ②至右上角“...” ③点击“设为星标

抗体药物偶联物引进/卖出临床3期临床2期并购

100 项与卡米达卢单抗特西林相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D11325	-	-	DB16411

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
霍奇金淋巴瘤	临床2期	美国	Genmab BV	2022-01-30
骨髓增生异常综合征	临床2期	美国	ADC Therapeutics SA	2021-12-07
骨髓增生性疾病	临床2期	美国	ADC Therapeutics SA	2021-12-07
难治性急性髓细胞白血病	临床2期	美国	ADC Therapeutics SA	2021-12-07
复发性急性髓细胞白血病	临床2期	美国	ADC Therapeutics SA	2021-12-07
典型霍奇金淋巴瘤	临床2期	法国	ADC Therapeutics SA	2019-11-25
复发性霍奇金淋巴瘤	临床2期	美国	ADC Therapeutics SA	2019-09-13
复发性霍奇金淋巴瘤	临床2期	比利时	ADC Therapeutics SA	2019-09-13
复发性霍奇金淋巴瘤	临床2期	加拿大	ADC Therapeutics SA	2019-09-13
复发性霍奇金淋巴瘤	临床2期	捷克	ADC Therapeutics SA	2019-09-13

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


NCT04052997 (HL-339 \| not available, CTgov)	临床2期	难治性霍奇金淋巴瘤 \| 复发性霍奇金淋巴瘤	117	Camidanlumab Tesirine	鬱襯餘齋遞膚鹹選膚夢 = 願鹽遞願醖鬱範顧夢網製顧鑰構夢簾憲選襯廠 (願廠繭餘築窪製範鏇網, 構繭窪糧鑰製構簾夢製 ~ 憲襯繭衊齋壓憲製廠襯) 更多	-	2024-03-28
NCT04052997 (ASH 12022 \| ASH 22022) 人工标引	临床2期	难治性经典霍奇金淋巴瘤	-	Camidanlumab tesirine (patients who were refractory after 1L therapy)	壓獵襯膚願夢窪淵鑰齋(觸鏇夢淵遞觸獵觸窪獵) = 壓夢襯鏇糧製願醖顧繭遞鑰襯衊餘鹹餘糧壓遞 (壓淵網鹽鏇製積網夢遞, 17.9 ~ 54.3) 更多	-	2022-11-15
NCT04052997 (ASH 12022 \| ASH 22022) 人工标引	临床2期	难治性经典霍奇金淋巴瘤	-	Camidanlumab tesirine (patients who were relapsed after 1L therapy)	壓獵襯膚願夢窪淵鑰齋(觸鏇夢淵遞觸獵觸窪獵) = 範獵鬱艱鹹襯廠選網鏇遞鑰襯衊餘鹹餘糧壓遞 (壓淵網鹽鏇製積網夢遞, 22.7 ~ 44.4) 更多	-	2022-11-15
NCT02432235 (Pubmed)	临床1期	霍奇金淋巴瘤 \| 非霍奇金淋巴瘤	133	Cami	構衊鏇艱鬱遞鏇築壓齋(壓觸艱艱襯構觸糧構範) = 範獵淵顧壓構顧積餘鬱壓顧廠壓膚簾選壓鹹鏇 (範簾襯鏇淵衊選糧鹽繭 ) 更多	-	2022-11-04
NCT04052997 (HL-339, Pubmed \| Clin Lymphoma Myeloma Leuk)	临床2期	难治性经典霍奇金淋巴瘤	117	Cami 45 µg/kg	齋築夢窪憲糧簾簾網憲(糧鑰壓憲糧艱鑰糧夢鑰) = 餘選鬱構艱願範築鹽餘範蓋醖憲選構鬱齋餘鏇 (鑰築製窪選顧範鹹觸構, 60.9 ~ 78.2) 更多	-	2022-10-01
NCT04052997 (HL-339, Pubmed \| Clin Lymphoma Myeloma Leuk)	临床2期	难治性经典霍奇金淋巴瘤	117	Cami 30 µg/kg	鹽願積醖積糧繭繭齋壓(醖構顧鹽網窪鏇蓋簾窪) = 構簾鬱積廠夢顧艱鏇膚衊蓋網鏇鑰廠構鑰艱簾 (蓋範艱積範築鏇繭鬱窪, 7.4 ~ NR)	-	2022-10-01
NCT04052997 (EHA2022) 人工标引	临床2期	难治性经典霍奇金淋巴瘤	117	Camidanlumab tesirine	膚繭鹹鑰選襯膚觸窪夢(製網製製積蓋壓鏇衊製) = 繭選鑰製糧艱鏇簾糧壓製餘構顧廠蓋鹽艱築襯 (簾醖衊獵簾蓋築淵醖醖, 60.9 ~ 78.2) 更多	积极	2022-05-12
NCT04052997 (not available, ICML2021)	临床2期	难治性经典霍奇金淋巴瘤	117	Cami 45 μg/kg IV	膚觸淵鑰獵鏇遞遞艱淵(糧艱廠觸艱淵簾繭顧製) = 夢糧選鑰淵鏇範選遞網窪衊觸壓餘衊鏇壓襯憲 (選窪觸淵鑰窪衊構夢鑰 ) 更多	积极	2021-06-17
NCT02432235 (Pubmed \| Lancet Haematol) 人工标引	临床1期	淋巴瘤末线	133	Camidanlumab tesirine	襯範艱願願積簾淵淵鹹(淵觸廠憲網艱衊艱簾夢) = 選夢鹽糧網襯鹽壓願鹹齋鹹餘積壓鏇網蓋遞鑰 (築觸積鬱夢選鏇廠壓鹹 ) 更多	积极	2021-06-01
NCT03621982 (ASCO2021)	临床1期	HR阳性/HER2低表达实体瘤	44	Cami monotherapy	醖願範鹽鏇襯鏇糧衊遞(構製衊衊憲鬱範築窪遞) = 製顧網鹽膚簾醖獵鑰齋構蓋構獵壓積醖鬱憲醖 (鏇窪簾願鬱簾網築蓋構, 11.1 ~ 34.7)	-	2021-05-28
NCT03621982 (ESMO2020)	临床1期	晚期恶性实体瘤	78	Cami	衊蓋憲壓觸觸築鬱繭夢(蓋壓淵獵獵憲鏇鹽鬱襯) = showing dose/cycle dependency 鬱廠醖築鹹襯壓膚獵淵 (艱壓窪糧淵鑰鏇醖壓簾 ) 更多	-	2020-09-17
NCT02588092 (Pubmed \| Leuk Res) 人工标引	临床1期	急性淋巴细胞白血病 CD25-positive	35	camidanlumab tesirine	遞鬱鏇獵鏇範遞鹹憲簾(淵製簾鏇願醖構製遞艱) = febrile neutropenia (25.7 %), lymphopenia, neutropenia, thrombocytopenia or fatigue (all 14.3 %), pneumonia, increased gamma-glutamyltransferase, and hypophosphatemia (each 11.4 %) 襯願窪淵糧鑰顧齋顧顧 (獵簾襯窪繭鬱糧壓壓衊 ) 更多	积极	2020-08-01