Multicenter, Open-label, Randomized, Phase 2 Study of Venetoclax and Azacitidine Plus Cusatuzumab Versus Venetoclax and Azacitidine Alone in Newly Diagnosed AML Patients Who Are Not Candidates for Intensive Therapy

The goal of this clinical trial is to learn if participants treated with the experimental drug cusatuzumab added to venetoclax and azacitidine works to treat acute myeloid leukemia (AML) compared to venetoclax and azacitidine. Venetoclax and azacitidine are drugs commonly used to treat AML in patients that are unable to receive chemotherapy to treat AML. The main question the clinical trial aims to answer is does cusatuzumab added to venetoclax and azacitidine prolong the length of time participants live compared to venetoclax and azacitidine?

开始日期2024-07-22

申办/合作机构

Oncoverity, Inc.

NCT04264806

/ Withdrawn临床2期

A Phase 2, Randomized, Open-label Study of Cusatuzumab in Combination With Azacitidine Compared With Azacitidine Alone in Patients With Higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) and Who Are Not Candidates for Hematopoietic Stem Cell Transplantation (HSCT)

The purpose of the study is to compare overall response rate (ORR) between treatment groups in participants with higher-risk Myelodysplastic Syndrome (MDS) or Chronic Myelomonocytic Leukemia (CMML) who are not eligible for Hematopoietic Stem Cell Transplantation (HSCT).

开始日期2021-05-06

申办/合作机构

Janssen Research & Development LLC

[+1]

CTIS2024-513276-17-00

/ Not yet recruiting临床1期

- ELEV20235

开始日期2020-08-11

申办/合作机构

Oncoverity, Inc.

100 项与 Cusatuzumab 相关的临床结果

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100 项与 Cusatuzumab 相关的转化医学

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100 项与 Cusatuzumab 相关的专利（医药）

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项与 Cusatuzumab 相关的文献（医药）

2023-11-01·The Lancet. Haematology

Cusatuzumab plus azacitidine in newly diagnosed acute myeloid leukaemia ineligible for intensive chemotherapy (CULMINATE): part one of a randomised, phase 2, dose optimisation study

Article

作者: Wei, Andrew H ; Doronin, Vadim ; Johnson, Amy J ; Xiu, Liang ; Hamad, Nada ; Gyan, Emmanuel ; Vey, Norbert ; Özcan, Muhit ; Nottage, Kerri ; Langlois, Angélique ; Demirkan, Fatih ; Ofran, Yishai ; Hultberg, Anna ; Herrera, Pilar ; Martinelli, Giovanni ; Müller, Rouven ; Jacobs, Julie ; Samoilova, Olga ; Trudel, Géralyn C ; Fogliatto, Laura M ; Pabst, Thomas ; Papayannidis, Cristina ; Arnan, Montserrat ; Guttke, Christina ; Ma, Xuewen ; Tolbert, Jaszianne A

BACKGROUND:

Cusatuzumab, a high-affinity anti-CD70 antibody, has shown preliminary activity as a treatment for acute myeloid leukaemia when combined with azacitidine. We aimed to determine the optimum dose for future trials of cusatuzumab in combination with azacitidine in patients with previously untreated acute myeloid leukaemia who are not eligible for intensive chemotherapy.

METHODS:

In this randomised, phase 2, open-label, dose-optimisation study we enrolled adult patients aged 18 years or older with newly diagnosed acute myeloid leukaemia not eligible for intensive chemotherapy, and with Eastern Cooperative Oncology Group scores of 0-2, from 40 hospitals and centres across seven countries. In part one of the trial, participants were randomly allocated 1:1 to 10 mg/kg or 20 mg/kg intravenous cusatuzumab on days 3 and 17, combined with subcutaneous or intravenous azacitidine 75 mg/m² on days 1-7 in 28-day cycles. The primary efficacy outcome was the rate of complete remission in the intention-to-treat group. The two dose cohorts were evaluated independently without between-cohort statistical comparison. Safety analyses were performed in all patients who received one dose of study drug. Part two of the trial was planned to be a single-arm expansion to evaluate cusatuzumab plus azacitidine at the cusatuzumab dose level selected in part one (primary hypothesis ≥35% rate of complete remission vs null hypothesis of 20%); however, changes in the acute myeloid leukaemia treatment landscape during this trial made it unlikely that enrolment to part two of the study would be clinically feasible, so the study stopped at the end of part one. The trial was registered at ClinicalTrials.gov, NCT04023526.

FINDINGS:

103 patients were enrolled between Aug 30, 2019, and Feb 25, 2020, and randomly assigned to either cusatuzumab 10 mg/kg (n=51) or 20 mg/kg (n=52). Median follow-up was 7·2 months (IQR 10·7 months). 57 of 103 (55%) patients were male and 46 (45%) patients were female, 78 (76%) were White, one (1%) was Asian, and 24 (23%) did not report their race. In the 10 mg/kg group, complete remission rate was 12% (six of 51 patients; 95% CI 6-23) and in the 20 mg/kg group was 27% (14 of 52; 17-40). Grade 3 or worse treatment-emergent adverse events (TEAEs) were similar between the cusatuzumab 10 mg/kg (n=51) and 20 mg/kg (n=51) cohorts and included thrombocytopenia (24 patients [47%] vs 29 [57%]), anaemia (24 [47%] vs 17 [33%]), and neutropenia (20 [39%] in both cohorts). Serious TEAEs were also similar in the two cohorts (44 [86%] vs 40 [78%]). Treatment-related TEAEs leading to death were reported in both groups (three patients [6%] in the 10 mg/kg group vs one patient [2%] in the 20 mg/kg group); the reported causes of death were pneumonia (n=2) and septic shock (n=2).

INTERPRETATION:

Although part one of this study was not designed to formally compare the two dose cohorts for efficacy, the totality of clinical data for cusatuzumab studies performed to date indicate that cusatuzumab 20 mg/kg plus azacitidine represents the optimal dose for further studies. A phase 1b study investigating the triple combination of cusatuzumab with venetoclax and azacitidine is underway (NCT04150887).

FUNDING:

Janssen Research & Development and argenx.

2023-10-01·Cell death and differentiation

METTL3 inhibition induced by M2 macrophage-derived extracellular vesicles drives anti-PD-1 therapy resistance via M6A-CD70-mediated immune suppression in thyroid cancer

Article

作者: Gao, Ming ; Zheng, Xiangqian ; Ruan, Xianhui ; Ning, Junya ; Zhang, Wei ; Hao, Jie ; Huang, Yue ; Hou, Xiukun ; Shi, Yi

The treatment options for advanced papillary thyroid cancer (PTC) and anaplastic thyroid cancer (ATC) refractory to standard therapies are limited. Although anti-PD-1 therapy has a manageable safety profile and has been effective in a small percentage of patients with advanced PTC and refractory ATC, the majority of the patients either do not respond or develop resistance to anti-PD-1 therapy. N6-methyladenosine (m6A) modification is a critical determinant of the complexity of the tumor microenvironment (TME). However, it is unclear whether and how m6A modification in tumor cells shapes the immune landscape of PTC and ATC. In this study, we performed bulk and single cell RNA sequencing analysis of PTC and ATC tissues, and found that low METTL3 expression not only correlated to poor response to immune checkpoint blockade (ICB) but was also associated with increased TNF family-related ligand-receptor interactions in the immunosuppressive Tregs and exhausted T cells. Furthermore, overexpression of METTL3 in PTC and ATC cells enhanced the efficacy of anti-PD-1 therapy in a peripheral blood mononuclear cell humanized NCG (huPBMC-NCG) mouse model. Mechanistically, M2 macrophage-derived extracellular vesicles (M2 EVs) inhibited METTL3 expression in PTC and ATC cells via miR-21-5p. Downregulation of METTL3 promoted demethylation of CD70 mRNA, which prevented YTHDF2-mediated degradation of the transcripts. The stabilization of CD70 mRNA, and the subsequent upregulation in CD70 protein levels increased the abundance of the immunosuppressive Tregs and terminally exhausted T cells, thereby inducing resistance to anti-PD-1 therapy. Furthermore, blocking CD70 using cusatuzumab, a high-affinity monoclonal antibody, reversed the anti-PD-1 therapy resistance induced by M2 EVs in vivo. Finally, we demonstrated that METTL3 expression negatively correlated with CD70 expression and M2 macrophages and Tregs infiltration in PTC and ATC tissues. Our findings provide new insights into developing novel therapies for advanced PTC and ATC.

2023-03-01·Cancer science

Cusatuzumab plus azacitidine in Japanese patients with newly diagnosed acute myeloid leukemia ineligible for intensive treatment

Article

作者: Hatayama, Tomoyoshi ; Shirahase, Toru ; Ikezoe, Takayuki ; Yamauchi, Takahiro ; Aida, Kensuke ; Usuki, Kensuke

Abstract:

We present the results of a phase 1 study that evaluated the safety, pharmacokinetics, pharmacodynamics, immunogenicity, and preliminary disease response to cusatuzumab, a novel anti‐CD70 monoclonal antibody, in combination with azacitidine, in newly diagnosed acute myeloid leukemia Japanese participants who were not candidates for intensive treatment. In this multicenter, single‐arm study, six participants were enrolled and treated. Only in cycle 1, participants received cusatuzumab monotherapy on day 14. Subsequently, cusatuzumab was administered intravenously on days 3 and 17 at 20 mg/kg in combination with azacitidine (75 mg/m2) on days 1‐7 of each 28‐day cycle. All six participants had at least one treatment‐emergent adverse event, and the most common treatment‐emergent adverse events (all grades) were leukopenia (four participants [66.7%]) and constipation (three participants [50.0%]). No dose‐limiting toxicity was observed during the study period. The combination of cusatuzumab and azacitidine is generally well tolerated in Japanese participants, and further exploration of this combination is warranted.

项与 Cusatuzumab 相关的新闻（医药）

2025-02-05

·Business Wire

CD70 Targeting Therapies Clinical Trials & Market Opportunity Insight 2025: Cusatuzumab Emerges as Leading Phase II Candidate for Leukemia Treatment, Paving the Way for CD70 Therapy Evolution - ResearchAndMarkets.com

DUBLIN--( BUSINESS WIRE )--The "CD70 Targeting Therapies Clinical Trials & Market Opportunity Insight 2025" report has been added to ResearchAndMarkets.com's offering. CD70 targeting therapies are rapidly gaining recognition as a promising strategy for the treatment of various cancers and immune-related disorders, significantly transforming the therapeutic landscape. CD70, a cell surface protein, is crucial in regulating the immune system, making it an optimal target for therapies designed to selectively attack diseased cells while preserving healthy tissues. This movement towards precision medicine is particularly vital in oncology, where traditional treatments such as chemotherapy and radiation often lead to severe side effects and limited effectiveness. Global CD70 Targeting Therapies Clinical Trials & Market Opportunity Insight 2025 Report Highlights: CD70 Targeting Therapies In Clinical Trials: > 20 Therapies CD 70 Targeting Therapies Clinical Trials Insight By Company, Country, Indication and Phase Insight On CD70 Targeting Therapy Technology Platforms FDA & EMA Designations Insight: Orphan, FTD, RMAT Designation Global & Regional Market Development Insight Combination Strategies For CD70 Targeting Therapies In clinical practice, CD70 targeting therapies are demonstrating considerable potential in treating hematological malignancies, particularly acute myeloid leukemia (AML), as well as solid tumors like renal cell carcinoma (RCC). AML is particularly challenging to manage with standard therapies, especially in patients who are unsuitable for intensive chemotherapy. Clinical trials focused on CD70 targeted therapies have shown promise in addressing this issue, with monoclonal antibodies and engineered cell therapies offering new hope for patients with few treatment options. The most advanced CD70-targeting therapy currently in clinical development is Cusatuzumab, created by argenx, which is presently undergoing Phase 2 trials in conjunction with chemotherapeutic agents for AML patients. This combination strategy seeks to enhance the effectiveness of Cusatuzumab by tackling resistance mechanisms and improving overall patient outcomes. The application of CD70 targeting therapies extends beyond cancer treatment. These therapies are also being investigated for autoimmune diseases, viral infections, and graft-versus-host disease (GvHD), although they remain in the early stages of research. In these contexts, where immune responses are dysfunctional, CD70 targeting agents hold the potential to modulate the immune system and restore normal immune function. The expansion of therapeutic applications significantly fuels interest in this sector, as it broadens the potential market for these treatments. In commercial terms, the US stands as hub for CD70 targeting therapy research and development. A robust ecosystem comprising biotechnology companies, pharmaceutical enterprises, and research institutions has driven the advancement of these therapies. Notable institutions such as Baylor College of Medicine, the National Institutes of Health, and cancer centers like City of Hope are conducting crucial clinical trials. Furthermore, regulatory support from the US FDA, including the Fast Track Designation for Adicet Bio's ADI-270 and the Regenerative Medicine Advanced Therapy designation for Allogene Therapeutics' ALLO-316, has expedited the development and commercialization processes. This regulatory endorsement is vital in facilitating access to new treatments, positioning the US as the heart for both clinical development and market introduction. China is emerging as a significant contender in the global CD70 targeting therapy landscape. The country's rapidly growing biotechnology sector, bolstered by increased investments and partnerships with international companies, has enabled swift advancements in innovative therapies. Chinese research institutions are increasingly involved in clinical trials, while local biotech firms are progressing towards the commercialization of CD70 targeting therapies. The intensifying competition within the CD70 targeting therapy market is fostering innovation, with several companies, including Allogene Therapeutics, Seagen (Pfizer), and CRISPR Therapeutics, developing novel treatments. These organizations are engaged in comprehensive preclinical and clinical research to assess the safety and efficacy of their therapies, thereby enhancing the therapeutic potential of CD70 targeted interventions. As more therapies enter clinical trials and yield favorable outcomes, the commercial opportunities for CD70 targeting therapies are expanding. In conclusion, the integration of favorable clinical results and a dynamic commercial landscape establishes CD70 targeting therapies as a crucial component of the future of precision medicine. As an increasing number of companies and research organizations dedicate resources to these therapies, their capacity to tackle a diverse array of diseases expands, indicating the prospect of both clinical and commercial achievements ahead. Key Topics Covered: 1. Introduction To CD70 Targeting Therapy 1.1 CD70 Targeting Therapy Overview 1.2 The Prerequisite For CD70 Targeting Therapy 1.3 Dual Role of CD70 As Diagnostic & Prognostic Biomarker 2. CD70 Targeting Therapeutic Approaches 2.1 Monoclonal Antibody 2.2 Bispecific Antibody 2.3 Tetraspecific Antibody 2.4 CAR T Cell Therapy 2.5 Antibody Drug Conjugate 2.6 CAR-NK Therapy 3. CD70 Targeting Therapies Clinical Research & Development By Indications 3.1 Leukemia 3.2 Lymphoma 3.3 Gynecologic Cancer 3.4 Renal Cell Carcinoma 3.5 Lung Cancer 3.6 Autoimmune & Inflammatory Disease 3.7 Viral Infections 4. Global CD70 Targeting Therapies Clinical Trials Overview 4.1 By Phase 4.2 By Country 4.3 By Company 4.4 By Indication 4.5 By Priority Status 4.6 Patient Segment 5. CD70 Targeting Therapies Regulatory Designations: Fast Track & Orphan Designation 6. Global CD70 Targeting Therapies Clinical Trials Insight 6.1 Preclinical 6.2 Phase I 6.3 Phase I/II 6.4 Phase II 7. CD70 Targeting Therapies Development Platforms By Company & Technology 7.1 AlloCAR T Platform 7.2 Gamma Delta Cell Platform 7.3 Tailwind Platform 7.4 DARPin Platform 7.5 SIMPLE Antibody Platform 7.6 Potelligent Technology 7.7 Off The Shelf Allogeneic Manufacturing 8. Global CD70 Targeting Therapies Current Market Trend & Developments 8.1 Current Market Outline 8.2 Future Market Forecast 9. CD70 Targeting Therapies Market Opportunity & Clinical Trends By Region 9.1 US 9.2 China 9.3 Europe 10. Combination Strategies For CD70 Targeting Therapies 10.1 In Combination With Immunotherapy 10.2 In Combination With Epigenetic Modulators 10.3 In Combination With Targeted Therapy 10.4 In Combination With Oncolytic Virus Therapy 10.5 In Combination With Chemotherapy 11. Global CD70 Targeting Therapies Market Dynamics 11.1 Market Drivers 11.2 Market Challenges 12. Competitive Landscape Adaptimmune (TCR2 Therapeutics ) Adicet Bio Allogene Therapeutics Ambrx (Johnson & Johnson) Chongqing Precision Biotech Chinook Therapeutics (Novartis) CRISPR Therapeutics ImmuneOnco Biopharma Pfizer Poseida Therapeutics For more information about this report visit https://www.researchandmarkets.com/r/9qx332 About ResearchAndMarkets.com ResearchAndMarkets.com is the world's leading source for international market research reports and market data. We provide you with the latest data on international and regional markets, key industries, the top companies, new products and the latest trends.

免疫疗法临床2期快速通道孤儿药细胞疗法

2024-11-22

·PipelineReview

OncoVerity Secures Extended Series A to Advance Cusatuzumab in Newly Diagnosed AML

First patients dosed in OV-AML-1231, a Phase 2 randomized controlled trial of cusatuzumab in newly diagnosed AML AURORA, CO, USA I November 21, 2024 I OncoVerity, a pioneer in applying advanced bioinformatics to drug development, announced today the closing of a Series A extension financing led by existing investors, argenx and RefinedScience. With this funding, OncoVerity aims to advance its mission to address the unmet medical need of cancer patients, leveraging a unique computational approach to inform a development strategy that seeks breadth and depth of response. The proceeds from the Series A extension will fund the Phase 2 OV-AML-1231 trial of cusatuzumab, a novel, first-in-class high-affinity monoclonal anti-CD70 antibody, in combination with venetoclax and azacitidine for the treatment of newly diagnosed acute myeloid leukemia (AML). The trial is enriched explicitly for patients with limited treatment options who show potential for responding to a cusatuzumab-based regimen, as informed by OncoVerity’s computational approach to guide its development. Patient enrollment is underway, and the first eight patients have been dosed. “This financing round is a critical step forward in accelerating the development of cusatuzumab,” said Max Colao, Chief Executive Officer at OncoVerity. “Cusatuzumab has the potential to treat a broad range of tumors, demonstrating a strong biologic rationale in AML. We are particularly excited about the potential of the Phase 2 trial, and look forward to sharing results from the interim analysis in the second half of 2025. These results will bring us closer to potentially offering a breakthrough new treatment option for AML patients. “This randomized phase 2 clinical trial was based on insights derived from machine learning-based approaches and will be analyzed using cutting-edge single cell omics technologies for depth and breadth of responses. This novel strategy was designed to optimize trial design and execution, address patient heterogeneity and other key patient specific needs and provide important insights into critical clinical and biologic areas. Together we hope this will help advance care for persons with AML and other cancers where there is urgent unmet medical need.” About OV-AML-1231 OV-AML-1231 is a randomized, open-label, multicenter, multinational, Phase 2 trial evaluating the safety and efficacy cusatuzumab combined with venetoclax, and azacitidine (VAC) to venetoclax and azacitidine (VA) in newly diagnosed AML patients not eligible for intensive chemotherapy. The planned enrollment is 120 newly diagnosed AML patients, randomized 2:1 to VAC (80 patients) and VA (40 patients). The trial population will be enriched for patients with adverse cytogenetic and molecular risk features. The primary end point is overall survival. Secondary endpoints include event-free survival, response rates including CR, CR+CRh, and rates of MRD negativity. About Cusatuzumab Cusatuzumab is a first-in-class high-affinity humanized monoclonal antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors, and severe autoimmune diseases. Cusatuzumab is designed to: block CD70, kill cancer cells expressing CD70 through complement-dependent cytotoxicity, enhance antibody-dependent cell-mediated phagocytosis, enhance antibody-dependent cell-mediated cytotoxicity, and restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532) . Cusatuzumab is currently being evaluated in patients with hematologic malignancies, including a Phase 2 trial in combination with azacitidine and a Phase 1b trial in combination with azacitidine and venetoclax in patients with newly diagnosed AML. About Acute Myeloid Leukemia Acute myeloid leukemia (AML) is a cancer of the bone marrow and the blood that progresses rapidly without treatment. It is a heterogeneous disease with variable prognosis for different patient subpopulations. Despite the advancements in medical research, there is still a significant need for new effective therapies to treat AML. The five-year survival rate for patients remains the lowest of all blood malignancies (5-20%), and relapse is common. Innovative therapies and targeted treatment approaches that can improve survival rates, reduce toxicity, and target specific subtypes of AML are urgently needed to address this unmet need. About OncoVerity OncoVerity is pioneering the use of computational tools applied to clinical and biological data to advance therapies that transform hope into reality for cancer patients. Through a strategic collaboration with Refined Science , OncoVerity’s approach leverages an advanced bioinformatics platform that applies single-cell multi-omics and machine learning technologies to a large AML patient database to identify biologic drivers to therapeutic resistance and insights on patient-specific risk factors. This approach not only holds promise for accelerating the development of cusatuzumab in AML, but also has the potential to be applied to its development in other hematologic malignancies, signifying a broader impact on the future of cancer treatment by bringing new hope to a wider range of patients. SOURCE: OncoVerity

临床2期免疫疗法

2024-07-20

·凯莱英药闻

宜明昂科：差异化设计寻求CD47突围之路！充足现金稳定支持公司重点项目推进

欢迎关注凯莱英药闻本月，宜明昂科发布公告，公司IMM01(替达派西普)与替雷利珠单抗联用，治疗程序性细胞死亡蛋白1(PD-1)抑制剂治疗后复发或病情有所进展的复发性或难治性(R/R)经典霍奇金淋巴瘤(cHL)患者的III期临床试验，已完成首例患者给药。IMM01是宜明昂科自主研发的新一代靶向CD47分子，是中国首个进入临床阶段的SIRPα-Fc融合蛋白，正被开发用于与其他药物联合治疗多种血液肿瘤和实体瘤。 CD47是一个关键的巨噬细胞检查点，在多种肿瘤细胞表面都有表达，其通过与巨噬细胞表面的SIRPα结合，传递“别吃我”信号，从而使其逃逸巨噬细胞的攻击；然而，在过去两年时间里，全球范围内不少药企都在CD47靶向药物的研发上折戟，其中包括吉利德、艾伯维、罗氏等MNC在内。据不完全统计，宜明昂科官网目前共披露了14款药物，其中推进最为靠前以靶向CD47单抗和双抗为主。宜明昂科的研发管线从创立之初，宜明昂科就被认为是“All in CD47”，这样的底气和信心从何而来？我们将从以下几个方面对公司和现有产品进行阐述。一公司及财务情况宜明昂科成立于2015年6月，是一家以科研为导向的生物技术公司，致力于开发肿瘤免疫疗法。公司利用先天和适应性免疫系统克服当前基于T细胞的免疫疗法的局限性，解决癌症患者大量未被满足的医疗需求。 2024年3月，宜明昂科公布2023年业绩，公司收入约38.6万元，研发开支增加5.3%至约2.92亿元，年内亏损约3.79亿元，同比收窄5.82%；每股亏损1.05元。这一业绩表明，‌尽管面临研发开支的增加，公司通过有效管理成本和资源，‌成功缩小了亏损额度；其研发开支增长主要归因于临床试验开支因临床候选药物的进展而增加，‌以及薪金及相关福利费用因临床团队的不断扩大而增加。‌这部分增加的开支部分被临床前及CMC开支减少所抵销。‌ 截至2023年12月31日，宜明昂科的现金及现金等价物（主要以美元、港元及人民币计值）、定期存款及按公允价值计量且其变动计入当期损益的金融资产合计为人民币6.09亿元。二研发平台公司已建立一体化的内部研发平台，具备靶点选择与验证、药物发现、高通量筛选、测试及临床前研究、CMC及IND注册能力；其专有平台使其能够持续探索和开发新一代创新肿瘤疗法并推动它们进入临床阶段，包括专有的单克隆抗体受体重组蛋白双特异性分子平台、先进的杂交瘤技术、高通量筛选、免疫测定和生物检测技术、高效的细胞系开发和抗体产能，以及强大的CMC和产能，使公司能够有效地进行药物筛选和成药性分析，经济高效地自主生产高质量的候选药物，为药物开发工作提供坚定的支持。三重点产品介绍 1、靶向CD47融合蛋白：IMM01 IMM01（Timdarpacept）基于宜明昂科自有研发平台研发、经基因修饰，具有全球自主知识产权的新一代CD47靶向分子，具有“Best-In-Class”的潜力。IMM01具有双重机制，能够同时阻断来自肿瘤的“别吃我”信号，并通过IgG1激活患者免疫系统的“吃我”信号。目前，IMM2520已获得中国NMPA、美国FDA批准开展临床试验；临床前毒性研究表明，IMM2520不与人体红细胞结合。在多种动物模型的体内试验中，IMM2520也展示出令人鼓舞的潜在疗效和安全性。 2024年6月，IMM01联合替雷利珠单抗治疗既往PD-(L)1抗体治疗失败后的cHL患者的II期更新数据显示：随访6.87个月，ORR达66.7%, CR 24.2%, DCR 93.9%，中位PFS和中位DOR未达到。在安全性上，绝大多数药物相关不良反应（TRAE）为1-2级的血液学的不良反应；其中3-4级的白细胞降低、血小板降低、中性粒细胞降低和贫血分别为12.1%、12.1%、12.1%和6.1%，在经过对症治疗后可完全恢复或者恢复至1级/基线水平；无溶血案例发生；无患者因TRAE导致永久停用研究药物或死亡。 2023 ASH上，公司更新了IMM01联合阿扎胞苷(AZA)治疗初治的CMML1-2型患者的数据，结果显示：ORR 72.7%，CRR 27.3%；治疗≥4个月的患者，ORR 达到87.5%，CRR 37.3%; 治疗超过≥6个月患者中, ORR达到83.3%, CRR 41.7%，疗效随着治疗时间延长而进一步提高。另外，IMM01联合AZA 治疗的安全性良好，不需要采用低剂量预激处理，对比AZA单药治疗数据，联合治疗没有增加毒性，没有出现新的药物安全信号。 2、靶向CD47/CD20双特异性分子：IMM0306 IMM0306（Amulirafusp alfa）是全球首个进入临床阶段的CD47×CD20双特异性分子，对CD20的亲和力高于CD47；相比起与CD47阳性的正常组织结合，该分子能优先同时与恶性B细胞上的CD20和CD47结合，并进一步减轻与CD47有关的毒性。目前，IMM0306正在开发用于治疗复杂性或难治性B细胞非霍奇金淋巴瘤(B-NHL)。 I期临床研究中，IMM0306单药显示出令人鼓舞的有效性和良好的安全性，8个剂量组中均没有观察到DLT。从0.8mg/kg开始至2.0mg/kg等四个剂量组，已观察到了5例CR，5例PR, 治疗复发难治性FL 的ORR 达到41%。同时，所有患者均没有出现明显的细胞因子风暴毒性。此外，IMM0306联合来那度胺的II期临床研究正在快速进行中，初步的临床表现令人激动。 3、靶向VEGF/PD-L1双特异性分子：IMM2510 IMM2510是基于宜明昂科“mAb-Trap”技术平台研发的、具有自主知识产权的双抗类药物，通过靶向免疫调节靶点PD-L1，阻断了PD-L1和PD-1的结合，解除了肿瘤细胞免疫逃逸，并通过Fc介导的ADCC/ADCP激活NK细胞及巨噬细胞从而发挥强大的肿瘤免疫治疗作用；同时，通过阻断VEGF/VEGFR信号通路，抑制肿瘤血管生成从而抑制肿瘤的生长和转移。临床前研究证实，IMM2510在多种肿瘤模型中均取得显著的治疗效果，IMM2510优于对应靶点的单药或针对两个靶点的联合用药，安全性上具有明显的优势。临床I期显示，IMM2510在爬坡研究中观察到复发难治的非小细胞肺癌(腺癌、鳞癌)以及胸腺癌中显现初步积极的疗效信号，尤其是一例肺鳞癌患者经过PD-1抗体治疗以及联合化疗方案失败后，获得明显肿瘤缩小(PR)，且PR超过11个月，接受研究用药已经超过20个月，目前还在接受治疗中。公司计划在单药以及联合不同治疗模式上，针对多个适应症做进一步开发，除软组织肉瘤外，还包括非小细胞肺癌、三阴乳腺癌，以及肝癌等常见肿瘤。 4、靶向CD47/HER2双特异性分子：IMM2902 IMM2902通过阻断HER2及CD47/SIRPα的抑制信号以及促进HER2降解，抑制肿瘤细胞的生长和增殖，并通过提高先天免疫反应进一步毁灭肿瘤细胞。2022年7月， IMM2902获得FDA授予针对乳腺癌的快速通道资格。临床前研究表明，在多种乳腺肿瘤和胃肿瘤模型（包括HER2低表达和曲妥珠单抗耐药肿瘤模型）中，IMM2902均表现出强大的抗肿瘤活性。公司正在中国和美国分别进行I期临床试验，以评估IMM2902在晚期HER2阳性及HER2低表达实体瘤（包括乳腺癌、胃癌、非小细胞肺癌及胆管癌）的安全性及有效性。 5、靶向CD47×PD-L1双特异性分子：IMM2520 IMM2520通过靶向肿瘤细胞上的CD47和PD-L1及其独特设计，可同时激活巨噬细胞及T细胞，以实现强大的协同作用并触发持久的肿瘤免疫反应。目前，IMM2520处于I期临床试验剂量递增阶段，已出现1例既往治疗复发的小细胞肺癌PR患者，展示出令人鼓舞的潜在疗效。临床前毒性研究表明，IMM2520不与人体红细胞结合。在多种动物模型的体内试验中，IMM2520也展示出令人鼓舞的潜在疗效和安全性。 6、靶向CD24单抗：IMM47 IMM47是一款具有全球首创潜力的靶向CD24用于癌症治疗的人源化单克隆抗体，凭借对肿瘤细胞上表达的CD24高特异性和高亲和力结合能力，IMM47能够阻断从CD24/Siglec-10通路传递至巨噬细胞、自然杀伤细胞(NK)和T细胞的免疫抑制信号。凭借基因工程技术改良的IgG1 Fc，IMM47通过强大的ADCP和ADCC有效激活巨噬细胞和自然杀伤细胞免疫反应。临床前动物体内药效研究中，IMM47能够显著提高肿瘤组织中M1巨噬细胞的数量以及下调肿瘤细胞CD24表达，单药或者和PD-1/PD-L1免疫检查点抑制剂等药物联用都显示出了令人鼓舞的抑制肿瘤生长能力。 7、靶向CD47/CD24双特异性分子：IMM4701 IMM4701通过宜明昂科的单克隆抗体-受体重组蛋白平台开发，与公司其他基于CD47的双特异性分子具有类似的结构。IMM4701具有稳健的抗肿瘤活性，在多种实体瘤模型中，IMM4701在3.0 mg/kg（~0.3 mg/kg人体等效剂量）时可实现122%的肿瘤生长抑制率(TGI)。 8、靶向CTLA-4抗体：IMM27M IMM27M具有增强的ADCC活性，可诱导靶向CTLA-4过度表达、具有免疫抑制作用的调节性T细胞的强效免疫反应，促进调节性T细胞从肿瘤微环境中清除，从而增强T细胞的抗肿瘤反应。临床前研究表明，IMM27M可诱导相比伊匹木单抗具有明显更强的抗肿瘤活性，且即使在低至0.3 mg/kg的剂量下达到肿瘤完全缓解，而该剂量伊匹木单抗仅表现出约50%的肿瘤生长抑制。 9、靶向CD70 单抗：IMM40H IMM40H可通过抑制CD70/CD27信号通路阻碍调节性T细胞的激活及增殖，是一款具有增强的ADCC活性的人源化单克隆抗体。体外细胞试验证明，IMM40H显示出较cusatuzumab更强的CD70结合亲和力，能够更有效地阻断CD70及CD27的相互作用。此外，IMM40H亦显示出强大的ADCC、补体依赖的细胞毒性(CDC)及ADCP活性，使对肿瘤细胞的强烈免疫攻击及潜在强效疗效。此外，临床前数据亦表明，IMM40H具有良好的安全性。参考资料 1、公司官网 2、财通证券、每日经济新闻、智通财经、财联社感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下

免疫疗法临床申请细胞疗法临床3期

100 项与 Cusatuzumab 相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
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研发状态

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适应症	最高研发状态	国家/地区	公司	日期
急性髓性白血病	临床2期	美国	Oncoverity, Inc.	2024-07-22
急性髓性白血病	临床2期	加拿大	Oncoverity, Inc.	2024-07-22
急性髓性白血病	临床2期	德国	Oncoverity, Inc.	2024-07-22
成人急性髓性白血病	临床2期	中国	argenx SE	2022-01-30
慢性粒单核细胞白血病	临床2期	澳大利亚	Janssen Research & Development LLC	2021-05-06
慢性粒单核细胞白血病	临床2期	巴西	Janssen Research & Development LLC	2021-05-06
慢性粒单核细胞白血病	临床2期	法国	Janssen Research & Development LLC	2021-05-06
慢性粒单核细胞白血病	临床2期	德国	Janssen Research & Development LLC	2021-05-06
慢性粒单核细胞白血病	临床2期	意大利	Janssen Research & Development LLC	2021-05-06
慢性粒单核细胞白血病	临床2期	俄罗斯	Janssen Research & Development LLC	2021-05-06

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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


NCT04023526 (CULMINATE, CTgov)	临床2期	急性髓性白血病 \| 急性早幼粒细胞白血病	103	Cusatuzumab+Azacitidine (Cusatuzumab 10 mg/kg Plus Azacitidine)	積簾構壓構壓觸簾艱廠(鏇襯糧網鹹製製膚顧餘) = 網窪鹹構淵窪觸鏇顧遞簾鏇鑰鬱齋廠壓鑰範淵 (憲鏇窪淵廠獵簾鏇願衊, 觸餘壓衊觸願獵願製鹽 ~ 膚積積襯築糧網顧壓繭) 更多	-	2024-07-30
				Cusatuzumab+Azacitidine (Cusatuzumab 20 mg/kg Plus Azacitidine)	積簾構壓構壓觸簾艱廠(鏇襯糧網鹹製製膚顧餘) = 鑰獵憲鬱夢衊製蓋蓋艱簾鏇鑰鬱齋廠壓鑰範淵 (憲鏇窪淵廠獵簾鏇願衊, 網鬱壓觸獵網餘壓鹽糧 ~ 壓網製膚廠獵觸廠獵選) 更多
NCT04023526 \| NCT04150887 (Pubmed \| Lancet Haematol)	N/A	急性髓性白血病	-	Cusatuzumab 10 mg/kg	夢獵壓鹹糧願鬱積築鑰(築窪鏇鬱餘窪淵構衊獵) = reported causes of death in the 10 mg/kg group: n=2 窪壓淵製齋鹽築壓廠繭 (遞壓廠鏇鑰築顧廠獵選 ) 更多	-	2023-11-01
				Cusatuzumab 20 mg/kg
NCT04023526 (CULMINATE, Corporate Publications) 人工标引	临床2期	急性髓性白血病	52	Azacitidine+cusatuzumab (cohort where patients received at least two treatment cycles)	醖範窪糧壓壓壓憲廠壓(蓋齋鏇簾窪繭餘製壓鏇) = 遞網願構糧衊選鏇醖簾壓淵糧築醖齋夢醖範醖 (艱廠餘製遞顧鏇繭簾膚 ) 更多	积极	2021-01-08
				Azacitidine+cusatuzumab (20 mg/kg)	醖範窪糧壓壓壓憲廠壓(蓋齋鏇簾窪繭餘製壓鏇) = 簾膚糧襯壓壓願選膚構壓淵糧築醖齋夢醖範醖 (艱廠餘製遞顧鏇繭簾膚 ) 更多
NCT03030612 (ASH 12018 \| ASH 22018) 人工标引	临床1/2期	急性髓性白血病一线	12	Azacitidine+Argx-110	製願願齋窪蓋夢顧獵鹹(積齋製遞艱壓鏇顧選蓋) = 願壓壓窪壓廠鑰顧醖壓鹹繭簾餘糧網構遞憲憲 (獵獵糧鏇醖範顧獵範壓 ) 更多	积极	2018-11-29
ICML2017	N/A	皮肤T细胞淋巴瘤	-	ARGX-110	繭製網鬱網夢構構廠鹽(願顧襯鹽鬱齋築選窪憲) = PR in 2 patients, with another 6 patient showing stable disease 觸蓋鏇獵製築齋範製膚 (繭壓鏇壓艱顧鹹艱艱廠 ) 更多	-	2017-06-07
NCT01813539 (ASCO2014)	临床1期	血液肿瘤	19	ARGX-110	憲選窪鹽願顧夢觸鏇夢(鬱廠鹽製範觸壓衊構遞) = 16% 獵衊構憲積遞鬱製蓋繭 (築製夢衊鏇餘鹹顧繭餘 ) 更多	-	2014-05-20