更新于：2024-12-14

Golcadomide Hydrochloride

更新于：2024-12-14

概要

研发状态

概要

基本信息

药物类型

分子胶

别名

2-[(3S)-2,6-dioxopiperidin-3-yl]-4-{[(2-fluoro-4-{[3-(morpholin-4-yl)azetidin-1-yl]methyl} phenyl) methyl]amino}-1H-isoindole-1,3(2H)-dione-hydrogen chloride、Golcadomide、BMS 986369

+ [6]

靶点

IKZF1 x IKZF3

作用机制

IKZF1抑制剂(DNA结合蛋白IKAROS抑制剂)、IKZF3抑制剂(锌指蛋白Aiolos抑制剂)

治疗领域

肿瘤免疫系统疾病血液及淋巴系统疾病+ [1]

在研适应症

大B细胞淋巴瘤滤泡性淋巴瘤复发性弥漫性大B细胞淋巴瘤+ [15]

非在研适应症-

原研机构

Celgene Corp.

在研机构

Celgene Corp.

Bristol Myers Squibb Co.

非在研机构-

最高研发阶段临床3期

首次获批日期-

最高研发阶段(中国)临床3期

特殊审评孤儿药 (欧盟)、孤儿药 (美国)

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结构

分子式C28H30FN5O5

InChIKeyNZYDBVQXOGPDDU-QHCPKHFHSA-N

CAS号2379572-34-4

关联

项与 Golcadomide Hydrochloride 相关的临床试验

CTIS2024-511304-16-00 / Recruiting

A Phase 2 Randomized, Open Label Study to Evaluate the Efficacy and Safety of Golcadomide in Combination with Rituximab in Patients with Newly Diagnosed Advanced Stage Follicular Lymphoma - CA073-1022

开始日期2024-10-14

申办/合作机构

Celgene Corp.

CTR20242203 / Recruiting临床3期

一项在未经治的高危大B细胞淋巴瘤受试者中对比Golcadomide联合R-CHOP化疗与安慰剂联合R-CHOP化疗的疗效和安全性的3期、多中心、随机、双盲、安慰剂对照研究

主要目的：在未经治的高危大B细胞淋巴瘤受试者中评价golcadomide+R-CHOP对比安慰剂-R-CHOP的研究者评估的PFS疗效。次要目的：在未经治的高危大B细胞淋巴瘤受试者中：评价golcadomide+R-CHOP对比安慰剂-R-CHOP的OS疗效、研究者评估的EFS疗效、IRAC评估的CMR疗效，以及EOT时MRD阴性的疗效。评价golcadomide+R-CHOP对比安慰剂-R-CHOP的IRAC评估的PFS疗效、研究者评估的OR疗效、研究者评估的CMR疗效、PFS24疗效、DoR疗效、PFS2疗效、CHOP细胞毒性组分的相对剂量强度暴露；通过EORTCQLQ-C30和FACT-LymS测量，比较golcadomide+R-CHOP与安慰剂-R-CHOP的疾病症状、功能和总体HRQoL。对比golcadomide+R-CHOP与安慰剂-R-CHOP的安全性。对比golcadomide+R-CHOP与安慰剂-R-CHOP治疗对HCRU的影响、对总体健康状况和效用的影响。

开始日期2024-09-03

申办/合作机构

百时美施贵宝（中国）投资有限公司

[+2]

NCT06425302 / Recruiting临床2期

A Phase 2 Randomized, Open Label Study to Evaluate the Efficacy and Safety of Golcadomide in Combination With Rituximab in Participants With Newly Diagnosed Advanced Stage Follicular Lymphoma

The purpose of this study is to assess the efficacy and safety of golcadomide in combination with rituximab in participants with newly diagnosed advanced stage Follicular Lymphoma (FL).

开始日期2024-08-30

申办/合作机构

Celgene Corp.

100 项与 Golcadomide Hydrochloride 相关的临床结果

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100 项与 Golcadomide Hydrochloride 相关的转化医学

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100 项与 Golcadomide Hydrochloride 相关的专利（医药）

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项与 Golcadomide Hydrochloride 相关的文献（医药）

2023-01-01·Blood reviews

Targeting cereblon in hematologic malignancies

Review

作者: Fuchs, Ota

The protein cereblon (CRBN) is a substrate receptor of the cullin 4-really interesting new gene (RING) E3 ubiquitin ligase complex CRL4^CRBN. Targeting CRBN mediates selective protein ubiquitination and subsequent degradation via the proteasome. This review describes novel thalidomide analogs, immunomodulatory drugs, also known as CRBN E3 ubiquitin ligase modulators or molecular glues (avadomide, iberdomide, CC-885, CC-90009, BTX-1188, CC-92480, CC-99282, CFT7455, and CC-91633), and CRBN-based proteolysis targeting chimeras (PROTACs) with increased efficacy and potent activity for application in hematologic malignancies. Both types of CRBN-binding drugs, molecular glues, and PROTACs stimulate the interaction between CRBN and its neosubstrates, recruiting target disease-promoting proteins and the E3 ubiquitin ligase CRL4^CRBN. Proteins that are traditionally difficult to target (transcription factors and oncoproteins) can be polyubiquitinated and degraded in this way. The competition of CRBN neosubstrates with endogenous CRBN-interacting proteins and the pharmacology and rational combination therapies of and mechanisms of resistance to CRL4^CRBN modulators or CRBN-based PROTACs are described.

2022-10-01·Clinical Lymphoma Myeloma & Leukemia

ABCL-412 Clinical Activity of CC-99282, a Novel, Oral, Small Molecule Cereblon E3 Ligase Modulator (CELMoD) Agent, in Patients With Relapsed/Refractory Non-Hodgkin Lymphoma (R/R NHL) –Results From CC-99282-NHL-001 (NCT03930953) a First-in-Human, Phase 1, Open-Label, Multicenter Study

Article

作者: Nastoupil, Loretta ; Guarinos, Carla ; Patah, Poliana ; Bachy, Emmanuel ; Feldman, Tatyana A ; Carpio, Cecilia ; Wu, Fan ; Buchholz, Tonia J ; Chou, Wen-Chi ; Kuruvilla, John ; Pourdehnad, Michael ; Michot, Jean-Marie ; Carrancio, Soraya ; Morillo, Daniel ; Ribrag, Vincent ; Li, Shaoyi ; Ferrari, Silvia ; Pinto, Antonio ; Chavez, Julio C

CC-99282, a CELMoD® agent, co-opts cereblon to induce targeted degradation of Ikaros/Aiolos. In preclinical studies, CC-99282 exhibited stronger antiproliferative, apoptotic, and immunostimulatory activities compared with lenalidomide and other CELMoD agents. Here we present results of CC-99282 monotherapy in patients with R/R NHL. This 2-part study comprises CC-99282 monotherapy dose escalation (part A) and expansion ± combination partners (part B). Part A includes patients with R/R diffuse large B-cell lymphoma (DLBCL) or follicular lymphoma (FL) that progressed after ≥2 lines of therapy (LOTs) and patients with R/R DLBCL unfit for transplant who have received ≥1 standard LOT. CC-99282 at 0.2, 0.4, 0.6, or 0.8 mg is administered once daily in 3 intermittent, 28-day cycle dosing schedules, with ≥3 patients per cohort. By October 6, 2021, 50 patients received CC-99282 in part A (38 DLBCL, 12 FL; median age 66y; 58% male; 3 median prior LOTs [range 1-8]); 17 remain on treatment, 26 discontinued due to progressive disease. Treatment-related grade 3/4 adverse events were observed in 32 (64%) patients, primarily neutropenia (29 [58%] patients) which was managed with dose modifications and granulocyte colony-stimulating factors. Grade 4 neutropenia during the first month of CC-99282 treatment correlated with prior therapy with ≥4 lines of alkylating agents. All dose-limiting toxicities were hematologic. Maximal recommended doses on the 7/14- and 14/28-days schedules of interest were 0.6 mg and 0.4 mg, respectively. For doses ≥0.4 mg on schedules of interest, responses were durable, and overall response rate was 42% (15/36 evaluable patients; 6 complete and 9 partial responses; 6 FL, 9 DLBCL); responders included patients who progressed on/after cellular therapy and/or immunomodulatory/CELMoD agents. Responses also correlated with early reduction in circulating tumor DNA. CC-99282 was absorbed rapidly with a prolonged median terminal half-life (~50 hours [doses ≥0.4 mg]). Increase in CC-99282 plasma exposure and Ikaros/Aiolos degradation in peripheral T cells were dose-dependent (maximum degradation [>90%] by treatment day 4 [doses ≥0.4 mg]). CC-99282 monotherapy demonstrated a manageable safety profile, with promising efficacy in heavily pretreated patients with R/R NHL. Pharmacokinetic/pharmacodynamic data were consistent with robust/rapid CC-99282-mediated antitumor activity. This BMS-funded study is enrolling patients.

2021-12-01·Bioorganic & medicinal chemistry letters4区 · 医学

Discovery of 3-amino-4-{(3S)-3-[(2-ethoxyethoxy)methyl]piperidin-1-yl}thieno[2,3-b]pyridine-2-carboxamide (DS96432529): A potent and orally active bone anabolic agent

4区 · 医学

Article

作者: Shinozuka, Tsuyoshi ; Nakao, Akira ; Nakai, Daisuke ; Nagai, Yoko ; Saito, Keiji ; Naito, Satoru ; Kunikata, Tomonori

The continuing investigation of SAR of 3-aminothieno[2,3-b]pyridine-2-carboxamide derivatives has been described. In this study, C4-piperidine derivatives with polar functional groups were synthesized to develop orally available bone anabolic agents. The optimized compound 9o (DS96432529), which exhibited the best PK profile and high in vitro activity, showed the highest in vivo efficacy in this series. Moreover, significant synergistic effects were observed following co-administration of DS96432529 and alendronate or parathyroid hormone. The mechanism of action is most likely mediated through CDK8 inhibition.

项与 Golcadomide Hydrochloride 相关的新闻（医药）

2024-11-28

·PRNewswire

Follicular Lymphoma Clinical Trial Pipeline Appears Robust With 50+ Key Pharma Companies Actively Working in the Therapeutics Segment | DelveInsight

Advances in immunotherapy have ushered in a new era of treatment for follicular lymphoma (FL), particularly for patients who have experienced relapse after conventional chemotherapy regimens. This paradigm shift is characterized by the emergence of innovative therapies like CAR T-cell therapy and bispecific antibodies, which have demonstrated remarkable efficacy in targeting and eradicating lymphoma cells. CAR T-cell therapy represents a groundbreaking approach where a patient's own T-cells are genetically engineered to recognize and attack cancer cells. This personalized treatment has shown significant promise, especially for individuals who have undergone extensive previous therapies. One notable example is Axicabtagene ciloleucel (Yescarta), a CAR T-cell therapy approved for use in patients with relapsed or refractory follicular lymphoma. Clinical trials have highlighted its ability to induce durable remissions, with some patients experiencing long-term remission even after multiple prior therapies. LAS VEGAS, Nov. 28, 2024 /PRNewswire/ -- DelveInsight's ' Follicular Lymphoma Pipeline Insight 2024 ' report provides comprehensive global coverage of pipeline follicular lymphoma therapies in various stages of clinical development, major pharmaceutical companies are working to advance the pipeline space and future growth potential of the follicular lymphoma pipeline domain. Key Takeaways from the Follicular Lymphoma Pipeline Report DelveInsight's follicular lymphoma pipeline report depicts a robust space with 50+ active players working to develop 55+ pipeline therapies for follicular lymphoma treatment. Key follicular lymphoma companies such as Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others are evaluating new follicular lymphoma drugs to improve the treatment landscape. Promising follicular lymphoma pipeline therapies such as Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others are under different phases of follicular lymphoma clinical trials. In August 2024, the company expects to file a supplemental Biologics License Application for tafasitamab for the treatment of patients with FL who have failed at least one prior systemic anti-CD20 immunotherapy or chemo-immunotherapy by the end of 2024 based on the positive Phase III results. In June 2024, a consortium of Eugene Private Equity and Korea Development Bank Private Equity announced that they would acquire 80% of South Korean vaccine maker Boryung Biopharma Co. for 320 billion won (USD 231 million). In February 2024, Incyte announced that it had entered into an asset purchase agreement with MorphoSys AG, which gives Incyte exclusive global rights for tafasitamab. Incyte will now recognize revenue and cost for all US commercialization and clinical development and MorphoSys will no longer be eligible to receive future milestone, profit split and royalty payments. In September 2023, OncoNano Medicine, Inc. announced a clinical trial supply agreement with Regeneron for the use of Libtayo (cemiplimab), a PD-1 inhibitor, in the combination stage of the first human trial of ONM-501, a dual-activating STING (STimulator of INterferon Genes) agonist and lead therapeutic development candidate. The ONM-501 first-in-human trial is a multicenter Phase Ia/b dose escalation and dose expansion study of intratumoral ONM-501 as monotherapy and in combination with Libtayo in patients with advanced solid tumors and lymphomas. OncoNano is the sponsor of the clinical trial, and Regeneron will supply cemiplimab. In May 2023, Janssen Pharmaceutical Companies of Johnson & Johnson announced that it had entered into a worldwide collaboration and license agreement with Cellular Biomedicine Group Inc. (CBMG) to develop, manufacture, and commercialize next-generation chimeric antigen receptor (CAR) T-cell therapies for the treatment of B-cell malignancies. Under the terms of the agreement, CBMG will grant Janssen a worldwide license to develop and commercialize the CAR-T assets, except in Greater China. Janssen and CBMG will negotiate an option for Janssen to commercialize the products in the Chinese territory. Janssen will make an upfront payment of USD 245 million that will be accounted for in the second quarter as a research and development expense. Additional future payments will be based upon achieving certain development, regulatory, and sales milestones, as well as tiered royalty payments on worldwide net trade sales, excluding Greater China. Request a sample and discover the recent advances in follicular lymphoma treatment drugs @ Follicular Lymphoma Pipeline Report The follicular lymphoma pipeline report provides detailed profiles of pipeline assets, a comparative analysis of clinical and non-clinical stage follicular lymphoma drugs, inactive and dormant assets, a comprehensive assessment of driving and restraining factors, and an assessment of opportunities and risks in the follicular lymphoma clinical trial landscape. Follicular Lymphoma Overview Follicular lymphoma is a common type of non-Hodgkin lymphoma (NHL) that originates from B-cells, a kind of white blood cell responsible for producing antibodies. This cancer is characterized by the growth of abnormal lymphoid follicles, which can disrupt normal lymphatic function. While the exact causes of follicular lymphoma are not fully understood, certain factors may increase the risk, including age (most commonly affecting adults over 60), a family history of lymphoma, and potential environmental factors such as exposure to pesticides or chemicals. Symptoms of follicular lymphoma can vary widely but may include painless swelling of lymph nodes in the neck, armpit, or groin, unexplained weight loss, night sweats, fatigue, and fever. Some patients may remain asymptomatic for extended periods, as this type of lymphoma can progress slowly. Diagnosis typically involves a combination of physical examinations, blood tests, imaging studies (like CT scans), and a biopsy of affected lymph nodes. The biopsy helps determine the subtype and stage of the lymphoma, which is crucial for planning treatment. Treatment for follicular lymphoma depends on the stage of the disease and the patient's overall health. Options may include watchful waiting for asymptomatic cases, chemotherapy, immunotherapy (such as monoclonal antibodies), and targeted therapies. In some cases, stem cell transplants may be considered for patients with more aggressive forms or those who do not respond to initial treatments. Given the indolent nature of follicular lymphoma, ongoing management, and regular monitoring are vital for achieving the best possible outcomes. Find out more about follicular lymphoma treatment drugs @ Drugs for Follicular Lymphoma Treatment A snapshot of the Follicular Lymphoma Pipeline Drugs mentioned in the report: Learn more about the emerging follicular lymphoma pipeline therapies @ Follicular Lymphoma Clinical Trials Follicular Lymphoma Therapeutics Assessment The follicular lymphoma pipeline report proffers an integral view of the follicular lymphoma emerging novel therapies segmented by stage, product type, molecule type, mechanism of action, and route of administration. Scope of the Follicular Lymphoma Pipeline Report Coverage: Global Therapeutic Assessment By Product Type: Mono, Combination, Mono/Combination Therapeutic Assessment By Clinical Stages: Discovery, Pre-clinical, Phase I, Phase II, Phase III Therapeutics Assessment By Route of Administration: Intra-articular, Intraocular, Intrathecal, Intravenous, Oral, Parenteral, Subcutaneous, Topical, Transdermal Therapeutics Assessment By Molecule Type: Oligonucleotide, Peptide, Small molecule Therapeutics Assessment By Mechanism of Action: Phosphatidylinositol 3 kinase delta inhibitors, Phosphatidylinositol 3 kinase gamma inhibitors, Emt protein-tyrosine kinase inhibitors, Interleukin 15 receptor agonists, Histone deacetylase inhibitors, Rad51 recombinase inhibitors, Agammaglobulinaemia tyrosine kinase inhibitors, Apoptosis stimulants, Cell cycle inhibitors, Tubulin inhibitors, Tubulin polymerisation inhibitors, Enhancer of zeste homolog 2 protein inhibitors, Antibody-dependent cell cytotoxicity, Programmed cell death 1 receptor antagonists, T lymphocyte stimulants, Alkylating agents, DNA cross-linking agents Key Follicular Lymphoma Companies: Chia Tai Tianqing Pharmaceutical Group, Incyte Corporation, Mabworks, Johnson & Johnson Innovative Medicine, Nektar Therapeutics, Xynomic Pharmaceuticals, Merck Sharp & Dohme, Jiangsu HengRui Medicine Co., Ltd., ADC Therapeutics, Bristol-Myers Squibb, Swedish Orphan Biovitrum, Zhejiang DTRM Biopharma, Immpact Bio, Galapagos, Immunitas Therapeutics, Enterome, CRISPR Therapeutics, CHO Pharma, Shanghai Blueray Biopharma, BeiGene, AstraZeneca, AVM Biotechnology, Mustang Bio, Merck, Pell Bio-Med Technology, Schrodinger Inc., Sana Biotechnology, Poseida Therapeutics, OncoNano Medicine, Inc., Nurix Therapeutics, Inc., NovalGen, Pfizer, Xencor, Wellington Zhaotai Therapies, MEI Pharma, Sutro Biopharma, Synthekine, Verismo Therapeutics, Vincerx Pharma, Novartis, Century Therapeutics, Newave Pharmaceuticals, Bio-Path Holdings, Affimed GmbH, Iksuda Therapeutics, Allogene Therapeutics, Adicet Bio, Carna Biosciences, Inc., BeiGene, Boryung Pharmaceutical, Accutar Biotechnology, Atara Biotherapeutics, AbbVie, InnoCare Pharma, NeoImmuneTech, and others. Key Follicular Lymphoma Pipeline Therapies: Parsaclisib, TQ-B3525, Tafasitamab, MIL62, Ibrutinib, AZD0486, NKTR-255, Abexinostat, Acalabrutinib, Zilovertamab vedotin, SHR2554, Nivolumab, Loncastuximab tesirine, Golcadomide, Emapalumab, DTRM-555, Capivasertib, IMPT 314, GLPG5101, IMT-009, EO2463, CTX112, CHO-H01, BR1733, BGB-16673, BGB-10188, AZD5492, AVM0703, MB106, MK-1026, PL001, SGR-1505, SC291, SC262, P-CD19CD20-ALLO1, ONM 501, NX-5948, NX 2127, NVG-111, Mevrometostat, Plamotamab, WZTL-002, Voruciclib, STRO001, SYNCAR-001 + STK-009, SynKIR-310, VIP-152, VAY736, CNTY-101, LP-168, BP1002, IOA-244, IKS 03, ALLO-501, ADI-001, AS-1763, BGB-21447, BR101801, AC676, ATA3219, ABBV-319, ABBV-101, ICP-B02, ICP-B05, C-CAR039, Efineptakin Alfa, and others. Dive deep into rich insights for new drugs for follicular lymphoma treatment, visit @ Follicular Lymphoma Drugs Table of Contents For further information on the follicular lymphoma pipeline therapeutics, reach out @ Follicular Lymphoma Treatment Drugs Related Reports Follicular Lymphoma Market Follicular Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key follicular lymphoma companies including Epizyme, Eisai, Bayer Healthcare Pharmaceuticals, Verastem Oncology, Gilead Sciences, TG Therapeutics, Bristol-Myers-Squibb, Roche, Incyte Corporation, Bristol Myers Squibb, ADC Therapeutics, MorphoSys, Nordic Nanovector, AbbVie, Regeneron Pharmaceuticals, Janssen Research & Development, Novartis, MEI Pharma, and BeiGene, among others. Non-Hodgkin Lymphoma Market Non-Hodgkin Lymphoma Market Insights, Epidemiology, and Market Forecast – 2032 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key Non-Hodgkin lymphoma companies, including Roche, Pfizer, Amgen, Novartis, Teva Pharmaceuticals, Genentech, ACD Therapeutics, among others. Non-Hodgkin Lymphoma Pipeline Non-Hodgkin Lymphoma Pipeline Insight – 2024 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Non-Hodgkin lymphoma companies, including Novartis, AstraZeneca, Genentech, BioInvent, Genmab, SystImmune, Nordic Nanovector, Pacylex Pharmaceuticals, Artiva Biotherapeutics, Inc., Chipscreen Biosciences, Ltd., Timmune Biotech Inc., Chia Tai Tianqing Pharmaceutical Group Co., Ltd., Gilead Sciences, Acerta Pharma BV, Adagene Inc, Conjupro Biotherapeutics, Inc., Rhizen Pharmaceuticals, Juventas Cell Therapy Ltd., Incyte Corporation, HUYA Bioscience International, SecuraBio, Genor Biopharma Co., Ltd., Kyowa Kirin Co., Ltd., Antengene Therapeutics Limited, Regeneron Pharmaceuticals, Jiangsu HengRui Medicine Co., Ltd., Xynomic Pharmaceuticals, Inc., BioTheryX, Inc., UWELL Biopharma, Kronos Bio, Bio-Thera Solutions, Spectrum Pharmaceuticals, Inc., Aptose Biosciences Inc., Miltenyi Biomedicine GmbH, Precision BioSciences, Inc., Teneobio, Inc., TCR2 Therapeutics, IGM Biosciences, Inc, among others. Diffuse Large B-cell Lymphoma Market Diffuse Large B-cell Lymphoma Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, market share of the individual therapies, and key DLBCL companies, including AbbVie, Genmab, Merck, Roche, Xencor, Janssen, Denovo Biopharma, Calithera Biosciences IMV, Biogen, Autolus Therapeutics, Allogene Therapeutics, Novartis, Miltenyi Biomedicine, Regeneron Pharmaceuticals, Debiopharm, Seagen, Takeda, AstraZeneca, Gilead Sciences, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

免疫疗法引进/卖出临床3期疫苗细胞疗法

2024-11-19

·医药观澜

2024年，这11款蛋白降解1类新药首次在中国获批临床！来自百济神州、华东医药等

▎药明康德内容团队报道靶向蛋白降解（TPD）技术的进展是药物发现领域的关键性转变，尤其是通过分子胶和蛋白降解靶向嵌合体（Proteolysis-Targeting Chimera，以下简称PROTAC），大大扩展了可成药的靶点，为治疗开辟了前所未有的可能性。当下，靶向蛋白降解领域正在蓬勃发展，新兴的技术和药物类型不断涌现。在中国，该领域今年以来也进展颇多，多款创新产品陆续进入临床阶段。根据NMPA药品审评中心（CDE）官网，今年以来（截至11月18日），至少有11款靶向蛋白降解疗法1类新药首次在中国获批IND，来自百济神州、华东医药、格博生物、睿跃生物、安斯泰来、百时美施贵宝等公司。这些产品拟开发的疾病领域涵盖实体肿瘤、血液肿瘤、自身免疫性疾病。本文将根据公开资料梳理这些产品的公开信息。格博生物：GLB-001胶囊作用机制：CK1α分子胶蛋白降解剂适应症：髓系恶性肿瘤 2024年2月，格博生物申报的GLB-001获批临床，拟开发用于髓系恶性肿瘤。GLB-001为格博生物自主研发的一款高选择性的酪蛋白激酶1α（CK1α）口服分子胶蛋白降解剂。GLB-001可通过与CRL4CRBN E3泛素连接酶复合物中的底物蛋白受体CRBN相结合，靶向降解CK1α，并触发p53的稳定与蓄积及其下游信号传导通路的激活，导致肿瘤细胞周期停滞和凋亡，发挥抑制肿瘤生长的作用。根据格博生物公开资料，该公司专注于靶向蛋白降解新药研发，成立至今已获得了高瓴创投、启明创投、礼来亚洲基金、凯泰资本和君联资本等多家知名投资机构近9000万美元融资。除了GLB-001胶囊，该公司研发的IKZF1/3选择性分子胶蛋白降解剂GLB-002此前也已经进入临床研究阶段。康朴生物：KPG-818胶囊作用机制：分子胶免疫调节药物适应症：系统性红斑狼疮 2024年3月，康朴生物研发的小分子1类新药KPG-818胶囊在中国获批临床，拟开发治疗系统性红斑狼疮（SLE）。KPG-818是康朴生物医药设计开发的新一代口服分子胶免疫调节药物，归属E3泛素连接酶复合物CRL4-CRBN调节剂，对靶点CRBN显示出极高的亲和力，可以高效降解与B淋巴细胞发育和增殖密切相关的锌指转录因子Aiolos（IKZF3）和Ikaros（IKZF1），有效调节TNF-α、IL-6、IL-2、IL-10等细胞因子的表达水平。值得一提的是，今年6月，KPG-818用于治疗系统性红斑狼疮的2a期临床研究结果已经发布。康朴生物是一家处于临床阶段的创新型生物医药公司，致力于开发小分子靶向免疫调节创新药物。该公司的研发管线中包含了CRL4-CRBN分子胶蛋白质降解剂产品，正在开发用于治疗系统性红斑狼疮、炎症性肠病、白塞氏病、多发性骨髓瘤等；还包括了多款处于临床前阶段的分子胶-抗体双重靶向药物。和径医药：HJ-002-03片作用机制：EGFR PROTAC 适应症：EGFR突变的晚期非小细胞肺癌今年4月和6月，和径医药研发的HJ-002-03片该产品相继在中国和美国获批临床，拟开发治疗EGFR突变的晚期非小细胞肺癌。HJ-002-03片是新一代口服、高选择性、广谱EGFR PROTAC，拟开发治疗EGFR突变晚期非小细胞肺癌。该产品旨在解决EGFR小分子抑制剂的耐药问题。和径医药聚焦肿瘤和中枢神经系统等疾病领域的药物开发，该公司研发管线涵盖PROTAC、抗体及小分子等。安斯泰来：ASP3082注射液作用机制：KRAS G12D PROTAC 适应症：KRAS G12D突变实体瘤 2024年6月，安斯泰来（Astellas）申报的ASP3082注射液在中国获批临床，拟开发用于携带KRAS G12D突变的既往经治局部晚期（不可切除）或转移性恶性实体瘤。公开资料显示，这是一款新型的小分子PROTAC，它结合并选择性靶向KRAS G12D突变蛋白，通过募集E3泛素连接酶蛋白进行降解。该产品正在国际范围内开展1期临床研究。根据安斯泰来官网介绍，该公司已经建立了一系列靶向蛋白降解剂研发管线，旨在创造下一代蛋白质降解物，用于治疗癌症和其它多个适应症。ASP3082正是该系列管线中的一款先导产品，其余还包括另一款KRAS G12D降解剂ASP4396以及一款尚处于临床前阶段的泛KRAS降解剂等。百时美施贵宝：golcadomide胶囊作用机制：CELMoD分子胶化合物适应症：大B细胞淋巴瘤 2024年6月，百时美施贵宝旗下新基（Celgene）公司1类新药golcadomide胶囊获批临床，拟开发用于未经治的高危大B细胞淋巴瘤。这是一款新型E3泛素连接酶Cereblon（CELMoD）分子，针对疾病特点做了优化，使其主要分布在淋巴器官。在针对B细胞淋巴瘤的1/2期临床研究中，该产品的客观缓解率（ORR）达到91.1%。百时美施贵宝公司的蛋白稳态（Protein Homeostasis）技术平台使用多种不同的方法来达到降解靶标蛋白的效果，其中包括被称为CELMoD的分子胶类化合物。它们通过与E3泛素连接酶Cereblon结合，改变其底物特异性，让它能够标记与癌症相关的蛋白，促使它们降解。超阳药业：HP-001胶囊作用机制：IKZF1/3分子胶降解剂适应症：血液系统恶性肿瘤 2024年7月，超阳药业1类新药HP-001胶囊获批临床，拟开发治疗血液系统恶性肿瘤。根据超阳药业新闻稿，HP-001胶囊是该公司首个1类创新药，为一款IKZF1/3分子胶降解剂。该产品属于新型CRBN E3连接酶调节剂，通过与CRBN结合，特异性招募转录因子IKZF1/3并启动对其蛋白的泛素化降解，激活多种抗肿瘤下游反应。超阳药业成立于2021年，该公司聚焦抗肿瘤适应症，已经搭建了包含多款分子胶和蛋白降解靶向嵌合体的研发管线。德亘生物：DG01片作用机制：双靶点 PROTAC 适应症：前列腺癌和肝癌等实体瘤 2024年8月，德亘生物申报的DG01片获批临床，拟开发治疗晚期或转移性去势抵抗性前列腺癌和肝癌等实体瘤。公开资料显示，DG01片为一款双靶点PROTAC药物。它可同时降解GSPT1和SRD5A3靶蛋白，双降解的作用机制诱导雄激素受体（AR）和AR-V7的下调，从而抑制前列腺癌细胞的增殖，达到治疗前列腺癌的效果。百济神州：BGB-45035片作用机制：靶向IRAK4的CDAC蛋白降解剂适应症：特应性皮炎 2024年8月，百济神州1类新药BGB-45035片获批临床，拟用于治疗中重度特应性皮炎。BGB-45035片是一款靶向IRAK4的蛋白降解剂，是百济神州在自有CDAC平台上研发的第二款靶向降解剂。该产品有潜力诱导更深、更快的IRAK4降解，并比其他同类药物具有更强的细胞因子抑制作用。IRAK4是Toll样受体（TLRs）和IL-1受体介导的炎症发生中的关键性蛋白。百济神州已经有多款CDAC产品进入临床研究阶段，除了BGB-45035片，还包括：包括BGB-16673（BTK CDAC），预计将于2025年上半年启动针对R/R CLL的3期临床试验；BG-60366（EGFR CDAC），近日已经向NMPA申报IND，有望在2024年第四季度进入临床开发阶段。睿跃生物：注射用CG009301 作用机制：GSPT1靶向蛋白降解剂适应症：血液恶性肿瘤 2024年10月，睿跃生物1类新药注射用CG009301获批临床，拟开发治疗复发/难治性血液恶性肿瘤（包括但不限于AML、ALL、高危型MDS等）。根据睿跃生物新闻稿介绍，CG009301是高选择性GSPT1靶向蛋白降解剂。GSPT1是一种在许多癌症中高度表达的蛋白质，包括血液学和实体瘤。睿跃生物（Cullgen）正在应用其专有的uSMITE™（ubiquitin-mediated, small molecule -induced target elimination）平台，通过小分子诱导、泛素化介导的方式将目标靶蛋白降解，使得传统基于功能位点抑制方式“不可成药”的蛋白可被靶向降解。该公司目前拥有三个降解剂项目正在或即将启动1期临床试验，还在推进其他几个靶向蛋白降解剂和降解剂-抗体偶联物（DACs）的研发。今年11月，睿跃生物宣布拟与Pulmatrix公司合并，旨在创建一家纳斯达克上市的公司。海创药业：HP568片作用机制：ERα PROTAC 适应症：ER+/HER2-乳腺癌 2024年10月，海创药业研发的1类新药HP568片获批临床，拟开展用于治疗ER阳性和HER2阴性的晚期乳腺癌的临床试验。HP568是一款靶向降解ERα的PROTAC药物，由靶蛋白配体、E3连接酶配体和两配体间的连接子3部分构成。研究表明该产品对ERα野生型蛋白和临床常见的ERα突变蛋白均具有极强的降解活性。海创药业专注于癌症和代谢性疾病领域新药研发，该公司拥有PROTAC靶向蛋白降解技术平台，目前其另一款口服AR PROTAC在研药物HP518已经进入临床研究阶段。华东医药：HDM2006片作用机制：HPK1 PROTAC 适应症：晚期实体瘤 2024年10月，华东医药1类新药HDM2006片获批临床，拟开发治疗晚期实体瘤。根据华东医药公告介绍，这是其首个自主研发的小分子抗肿瘤药物，为一款靶向造血祖激酶1（HPK1）的PROTAC药物。HPK1位于PD-1的上游通路，是免疫细胞表达的关键激酶，有可能成为免疫治疗的下一个潜力靶点。相较于HPK1小分子抑制剂，蛋白降解剂有望大幅提升药效和安全性。根据今年10月《自然》子刊Nature Reviews Drug Discovery近期发布的综述文章介绍，靶向蛋白降解剂的发现与设计仍面临诸多挑战，尤其在识别和验证适合降解的靶点方面。同时，识别新的E3连接酶也需要大量的发现与验证工作。尽管存在诸多挑战，但随着产业和学术界在科学与技术上的不断突破与创新，靶向蛋白降解技术有望在未来带来更多新药获批，造福广大患者。参考资料： [1]中国国家药监局药品审评中心（CDE）官网. Retrieved Nov 18，2024, From https://www.cde.org.cn/main/xxgk/listpage/4b5255eb0a84820cef4ca3e8b6bbe20c [2]各公司官网及公开资料本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权或其他合作需求，请联系wuxi_media@wuxiapptec.com。免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。

蛋白降解靶向嵌合体临床申请临床1期

2024-11-18

·Business Wire

Foresight Diagnostics to Present New Data on Foresight CLARITY™ Ultra-Sensitive MRD Detection Across Multiple Studies at the 66th American Society of Hematology Annual Meeting

BOULDER, Colo.--( BUSINESS WIRE )-- Foresight Diagnostics , a leader in ultrasensitive minimal residual disease (MRD) testing, today announced the presentation of multiple studies showcasing Foresight CLARITY™ MRD at the upcoming 66 th American Society of Hematology Annual Meeting and Exposition taking place December 7-10 in San Diego, California. The presentations span various lymphoma types and treatment settings, demonstrating the broad applicability of the Foresight CLARITY MRD detection technology for monitoring treatment response and predicting patient outcomes. The studies include collaborations with multiple pharmaceutical companies and research institutions, including AstraZeneca, Bristol Myers Squibb (BMS), Daiichi Sankyo (DSI), Stanford University, Washington University, and others. "These studies add to the growing body of evidence supporting ultra-sensitive MRD testing as a critical tool in lymphoma care and drug development," said David Kurtz, MD, PhD, Chief Medical Officer and Head of Research at Foresight Diagnostics. "We see in these studies that MRD measurement with Foresight CLARITY consistently enables earlier and more accurate treatment response assessment than conventional imaging-based methods. The ability to monitor disease status in real-time with ultra-sensitive MRD assays like Foresight CLARITY may help accelerate clinical trials and lead to more personalized decision-making for patient care." Results utilizing Foresight CLARITY MRD technology are featured in six abstracts, including three that are co-authored by Foresight. Presentation highlights include: LBCL/DLBCL: ctDNA-MRD as a surrogate endpoint for 2L CAR T – Analysis of the Phase 3 TRANSFORM trial in second-line treatment for large B-cell lymphoma (LBCL) reinforced the potential of circulating tumor DNA (ctDNA) as an earlier endpoint for response assessment and assessment of clinical trial results. In the TRANSFORM study, patients receiving lisocabtagene maraleucel (liso-cel) had significantly improved event-free survival compared to standard of care. Consistent with this result, patients receiving liso-cel also demonstrated higher rates of MRD clearance, demonstrating CLARITY's ability to measure differential treatment responses. MRD Response with novel first-line therapy in high-risk DLBCL – Analysis of a Phase 1b trial CC-220-DLBCL-001 combining golcadomide with R-CHOP in previously untreated aggressive B-cell lymphoma showed promising MRD clearance rates. The data demonstrated that 90% of patients achieved MRD negativity at end of treatment with golcadomide 0.4mg + R-CHOP, with strong responses observed even in high-risk patients. These data further support the ongoing Phase 3 GOLSEEK-1 study investigating this novel combination therapy in high-risk 1L LBCL. Enhanced risk stratification by MRD vs. traditional methods – New research investigates the predictive value of the International Prognostic Index (IPI), currently the primary pre-treatment risk assessment tool for DLBCL. The study revealed that pre-treatment IPI scores did not significantly correlate with end-of-treatment MRD status, with MRD testing being a superior predictor of progression-free survival. Follicular Lymphoma: MRD-based response assessment of novel FL therapies – Two studies demonstrated the value of MRD assessment in follicular lymphoma trials, with new treatment approaches showing early clearance. The CD19xCD3 bispecific antibody AZD0486 achieved 89% MRD negativity in relapsed or refractory FL patients by 12 weeks in complete responders. In the 1L setting, the chemotherapy-free combination of mosunetuzumab and polatuzumab vedotin showed similar early MRD clearance, with 7 of 8 complete responders achieving MRD negativity before cycle 3. These results highlight the potential for MRD as an early indicator of therapeutic response in FL clinical trials. PTCL: ctDNA as a prognostic biomarker for T-cell lymphoma – Analysis from the VALENTINE-PTCL01 Phase 2 trial in relapsed/refractory peripheral T-cell lymphoma (PTCL) revealed that patients achieving early, deep ctDNA reduction (>5-fold decrease by Cycle 2 Day 1) experienced significantly longer progression-free survival, establishing ctDNA monitoring as a powerful tool for early response assessment. Information on abstract presentation time and dates can be found below. To meet with Foresight Diagnostics, visit booth #3423 or contact us at BD@foresight-dx.com. Oral Presentations: Circulating Tumor DNA (ctDNA) as an Early Outcome Predictor in Patients with Second-Line Large B-Cell Lymphoma After Lisocabtagene Maraleucel Versus Standard of Care Treatment from the Phase 3, Randomized TRANSFORM Study Presenter: Ash Alizadeh, MD, PhD (Stanford University) Session 628 Date/Time: Saturday, December 7, 2024, 10:45 a.m. Sponsor: Bristol Myers Squibb Co-authored by Foresight Diagnostics Escalating Doses of AZD0486, a Novel CD19xCD3 T-Cell Engager, Result in High Complete Remissions with Rapid Clearance of Minimal Residual Disease in Patients with Relapsed/Refractory Follicular Lymphoma Presenter: Jing-Zhou Hou, MD, PhD (UPMC Hillman Cancer Center) Session 623 Date/Time: Saturday, December 7, 2024, 5 p.m. Sponsor: AstraZeneca Golcadomide (GOLCA) Plus R-CHOP Has High Minimal Residual Disease (MRD) Negativity across High-Risk, Untreated Aggressive B-Cell Lymphoma (a-BCL) Presenter: Jason R. Westin, MD (MD Anderson) Session 627 Date/Time: Sunday, December 8, 2024, 12:30 p.m. Sponsor: Bristol Myers Squibb International prognostic index poorly predicts EOT ctDNA MRD status in DLBCL and has limited impact on its predictive value for outcomes Presenter: Jordan S. Goldstein, MD, MS (Stanford University) Session 626 Date/Time: Sunday, December 8, 2024, 5 p.m. Co-authored by Foresight Diagnostics Poster Presentations: Prediction of Clinical Response by Phased Variants in Circulating Tumor DNA (ctDNA) in the VALENTINE-PTCL01 trial of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Presenter: Neha Mehta-Shah, MD, MSCI (Washington University) Abstract #4342, Session 621 Date/Time: Monday, December 9, 2024, 6-8 p.m. Sponsor: Daiichi Sankyo Co-authored by Foresight Diagnostics Mosunetuzumab Plus Polatuzumab Vedotin Induces Early Complete Responses in Previously Untreated High Tumor Burden Follicular Lymphoma Presenter: David A Russler-Germain, MD, PhD (Washington University) Abstract #4414, Session 623 Date/Time: Monday, December 9, 2024, 6-8 p.m. About Foresight Diagnostics Foresight Diagnostics is a privately-held cancer diagnostics company and CLIA-registered laboratory. Its liquid biopsy platform, Foresight CLARITY™, is a novel assay that measures minimal residual disease (MRD) with reported detection limits in parts per million 1. The improved sensitivity of Foresight CLARITY has the potential to provide actionable information to physicians and biopharmaceutical companies to enable more personalized treatment approaches for patients with solid tumor and hematologic malignancies. For more information, please visit foresight-dx.com and follow us on Twitter and LinkedIn. Foresight CLARITY™ IUO is an investigational device. Limited by United States Law to investigational use. 1 Foresight CLARITY™ IUO is an investigational device. Limited by United States Law to investigational use.

临床结果临床3期ASH会议

100 项与 Golcadomide Hydrochloride 相关的药物交易

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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
大B细胞淋巴瘤	临床3期	美国	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	日本	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	阿根廷	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	澳大利亚	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	奥地利	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	巴西	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	保加利亚	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	加拿大	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	智利	Bristol Myers Squibb Co.	2024-06-19
大B细胞淋巴瘤	临床3期	哥伦比亚	Bristol Myers Squibb Co.	2024-06-19

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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


ASH2024	N/A	滤泡性淋巴瘤	-	GOLCA mono	鬱襯廠顧餘壓簾選窪廠(襯鹽鏇積繭餘構蓋顧膚) = The most frequent grade (G) 3+ TEAEs were neutropenia (44%) and anemia (12%). The incidence of febrile neutropenia was 7%. Serious adverse events occurred in 30% of pts, with febrile neutropenia and pneumonia being the most common, in 2 pts (5%) each, as well as pulmonary embolism in 1 pt. Neutropenia led to GOLCA dose interruption in 4 pts (9%) and dose reduction in 1 pt. No pts discontinued treatment because of GOLCA-related TEAEs. Non-hematological TEAEs (e.g., GI toxicity, rash, fatigue) were all low-grade (except 1 pt with G3 fatigue). There were no new safety signals identified for GOLCA mono (part A) at the 30-mo follow up period. 築築窪遞鬱廠餘簾願鬱 (獵淵膚顧廠範鏇淵製製 ) 更多	-	2024-12-08
ASH2024	N/A	滤泡性淋巴瘤	-	GOLCA + RTX 0.2 mg		-	2024-12-08
ASH2023	临床1期	B细胞淋巴瘤	78	GOLCA plus R-CHOP	鬱齋憲壓艱鬱構壓觸糧(願鹽鹽顧範膚齋網齋窪) = 繭壓願艱鹽獵鏇襯觸構獵繭簾製壓築窪襯壓鑰 (壓衊餘鹹製構構網願衊, 80.4 ~ 97.0) 更多	-	2023-12-11
ASH2023	临床1期	B细胞淋巴瘤	-	Golcadomide (CC-99282) + R-CHOP	顧餘衊窪顧網衊範壓繭(夢鏇淵觸襯憲襯繭鑰窪) = 艱餘襯製鏇艱淵糧襯選餘鹽鹽網窪窪齋醖窪廠 (鬱艱衊蓋鹹鹹鑰積艱顧 )	-	2023-12-09