A Phase 1, Open-Label Study in Healthy Volunteers to Evaluate the Relative Bioavailability of NX-5948 Tablets Compared to Capsules, and the Effect of Food and an Acid-reducing Agent on the Pharmacokinetics of NX-5948

This is a 2-cohort, fixed-sequence, 3-period, relative bioavailability, food-effect, and drug-drug interaction study. It is an open-label study evaluating the relative bioavailability of NX-5948 tablets compared to capsules, and the effect of food and an acid-reducing agent on the pharmacokinetics (PK) of NX-5948.

开始日期2024-11-30

申办/合作机构

Nurix Therapeutics, Inc.

NCT06691828 / Recruiting临床1期

A Phase 1, Open-Label, 2-Period, Fixed-Sequence Study to Assess the Absolute Bioavailability, Absorption, Metabolism, Excretion, and Mass Balance of [14C]-NX-5948 in Healthy Males

This is a Phase 1, 2-period, open-label, single-dose, fixed-sequence study to assess the absolute bioavailability, absorption, metabolism, excretion, and mass balance of [14C]-NX-5948. Period 1 will analyze PD (pharmacodynamics) and exploratory biomarkers. Period 2 will analyze total radioactivity and metabolite profiling.

开始日期2024-11-01

申办/合作机构

Nurix Therapeutics, Inc.

NCT06593457 / Active, not recruiting临床1期

A Phase 1, 2-Part, Placebo-Controlled, Double-Blinded Study to Assess the Effect of Food and Drug-Drug Interaction of Fluconazole on the Pharmacokinetics of NX-5948

This is a Phase 1, 2-part double-blinded (with respect to NX-5948/placebo), placebo-controlled study. Part 1 is a randomized, 3 period cross-over food-effect (FE) and drug-drug interaction (DDI) study. Part 2 is a single-period PK evaluation study.

开始日期2024-08-20

申办/合作机构

Nurix Therapeutics, Inc.

100 项与 NX-5948 相关的临床结果

登录后查看更多信息

100 项与 NX-5948 相关的转化医学

登录后查看更多信息

100 项与 NX-5948 相关的专利（医药）

登录后查看更多信息

项与 NX-5948 相关的文献（医药）

2023-03-30·Blood

The cat-and-mouse game of BTK inhibition.

Communications

作者: Portelinha, Ana ; Wendel, Hans-Guido

In this issue of Blood, Zhang et al¹ report the preclin. efficacy of a new Bruton tyrosine kinase (BTK) degrader mol. (NRX-0492, a close relativeOf the clin. compounds NX-2127 and NX-5948)² to overcome BTK inhibitor resistance.The authors show that NRX-0492 degrades wild-type and C481 mutant BTK, resulting in significant single-agent activity against chronic lymphatic leukemia (CLL) patient-derived xenografts in vivo.¹A closely related compound, NX-2127,² is now in clin. trials in B-cell malignancies (NCT04830137).

项与 NX-5948 相关的新闻（医药）

2024-12-10

·EndPoints

Early data on BTK degraders suggest promise of next-gen approach

SAN DIEGO — Drug developers are making a new generation of treatments for blood cancers that arise from abnormal B cells by taking advantage of the body’s natural protein recycling system. BeiGene reported Sunday that its BTK degrader led to a 78% response rate across a range of doses in 49 patients with chronic lymphocytic leukemia. Many of the patients in the Phase 1 study had previously tried at least one of the commercially available BTK inhibitors. In particular, the company highlighted the 200 mg dose, with 15 of 16 patients responding to treatment. Mehrdad Mobasher, BeiGene’s CMO for hematology, said the BTK degrader’s advantage is that it can tackle both the wild type and mutant forms of BTK — and that includes “resistance mutations to covalent BTKs, resistance mutations to non-covalent BTKs, even the ones that we call kinase dead [BTK mutations], because it degrades the scaffolding of the protein.” There was one instance of dose-limiting toxicity that occurred when one patient experienced a grade 3 rash and required a five-day treatment hold in the 200 mg dose arm. Thirteen patients experienced grade 3 or higher neutropenia. Degraders of BTK, or Bruton’s tyrosine kinase, work by attaching to the BTK protein as well as what’s known as E3 ligase — an enzyme that leads proteins to get broken down by the body. The degraders follow a class of highly successful BTK inhibitors that includes drugs like BeiGene’s Brukinsa, Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence, and Eli Lilly’s Jaypirca. Nurix Therapeutics also reported a Phase 1a/1b update for its BTK degrader and said it plans to launch pivotal trials for NX-5948 in 2025. The follow-up builds on data in chronic lymphocytic leukemia released earlier this year , but this time it’s evaluating more patients for a longer period. Among 49 evaluable CLL and small lymphocytic lymphoma patients, 75.5% responded to NX-5948 across all doses, with a majority of responses occurring at the first eight-week assessment. However, Nurix said the response increased to 84.2% with longer time on treatment, “based on an exploratory efficacy analysis of patients who had at least two response assessments” at week 16. The patient group was heavily pretreated, with a vast majority having already received a prior BTK inhibitor. The company noted that a “large number” of patients had mutations associated with resistance to BTK inhibitors. “With a greater number of patients and longer duration of treatment, we are highly encouraged to see a deepening of therapeutic responses over time while maintaining a favorable safety profile,” Nurix CMO Paula O’Connor said in a news release. Safety was evaluated across 125 patients in all dose escalation and expansion cohorts in the trial, including some patients with non-Hodgkin lymphoma. Nurix said the drug was “well tolerated across all doses evaluated,” highlighting that there was just one case of grade 1 atrial fibrillation in a patient whose condition was preexisting. Cardiovascular toxicities have been a concern in the BTK inhibitor class. The company is currently enrolling the Phase 1b portion of the trial.

临床结果临床1期

2024-12-10

·凯莱英药闻

ORR高达84.2%！Nurix公布新一代BTK降解剂治疗复发/难治性CLL/SLL患者的积极临床数据

欢迎关注凯莱英药闻 2024年12月9日，Nurix Therapeutics在2024 年 12 月 7 日至 10 日在加利福尼亚州圣地亚哥举行的第 66 届美国血液学会 (ASH) 年会和博览会上，展示了NX-5948的最新临床研究数据。 NX-5948是一种布鲁顿酪氨酸激酶 (BTK) 降解剂，目前正在对患有复发或难治性 B 细胞恶性肿瘤的成年人进行 1a/b 期临床试验评估。关于最新研究数据截至 2024 年 10 月 10 日，共有60 名复发或难治性慢性淋巴细胞白血病或小淋巴细胞淋巴瘤 (CLL/SLL) 患者入组。这些CLL/SLL 患者此前接受过包括共价BTK 抑制剂（98.3%）、淋巴细胞瘤-2基因 (BCL2) 抑制剂（83.3%）和非共价 BTK 抑制剂（28.3%）治疗；大量患者具有与 BTK 抑制剂耐药性相关的突变，包括 BTK（38.6%）和 PLC2G（12.3%）的突变。在可评估疗效的 CLL/SLL 患者（n=49）中，NX-5948 治疗在所有测试剂量中均获得了 75.5% 的稳健客观缓解率 (ORR)，大多数缓解发生在第一次评估（第 8 周）时；随着治疗时间的延长，至少接受过两次反应评估（第 16 周）的患者ORR 增加至 84.2%。所有人群均观察到反应，包括基线 BTK 突变，以及对共价和非共价 BTK 抑制剂治疗耐药性的患者。在所有评估剂量下均具有良好的耐受性，在 CLL/SLL 患者中，最常见的治疗出现的不良事件是紫癜/挫伤（36.7%，均为 1 级或 2 级）、疲劳（26.7%，均为 1 级或 2 级）、瘀点（26.7%，均为 1 级或 2 级）、中性粒细胞减少症（23.3%，18.3% 为 3 级或更高）和皮疹（23.3%，1.7% 为 3 级或更高）。整个人群只有一例1级心房颤动患者（患者已有心房颤动）发生。关于NX-5948 NX-5948 是一种口服生物可利用、脑渗透性、BTK小分子降解剂，通过cereblon E3连接酶复合体介导的泛素化和随后的蛋白酶降解，诱导BTK的野生型和突变型的特异性降解，对当前 BTK 抑制剂疗法有抗药性的肿瘤细胞系具有很强的效力。 2024年1月，FDA已授予 NX-5948 快速通道资格，用于治疗复发或难治性CLL/SLL的成年患者；上述患者此前至少经历两种疗法，包括BTK抑制剂和BCL2抑制剂。 2024年10月，公司在第 12 届华氏巨球蛋白血症国际研讨会 (IWWM-12) 上，公布旗下NX-5948在治疗包括复发/难治性华氏巨球蛋白血症 (WM)的1a/1b 期临床试验积极数据，结果显示：（1）9 名可评估疗效的WM 患者中，7 名患者 (77.8%) 有客观反应，2 名患者病情稳定 (22.2%)。（2）所有 7 名患者均在 8 周的首次评估中出现反应，5 名患者仍在接受治疗，2 名患者接受治疗超过一年。（3）无论患者基线 MYD88 和CXCR4突变如何，均观察到反应。（4）以血清 IgM 水平的降低为衡量指标，NX-5948 的疗效可随着时间的推移而加深。此外，本次会议还披露了NX-5948在原发性中枢神经系统淋巴瘤 (PCNSL) 动物模型中的新临床前数据，显示：（1）NX-5948 可促进BTK 的强力降解、抑制细胞外信号调节激酶 (ERK) 并延长PCNSL患者的生存期。（2）在接受 NX-5948 治疗的动物中，观察到与增强肿瘤抗原呈递和减少肿瘤进展相关的转录变化。关于BTK降解剂 BTK是一种非受体蛋白酪氨酸激酶（NRTK），属于TEC激酶家族，在B细胞表面受体(BCR)等信号传导通路中发挥重要作用。生理情况下，BTK参与B细胞的发育成熟，以及B细胞的增殖、运输、趋化、黏附等过程。在CLL/SLL等多种B细胞血液瘤中，BTK持续激活下游AKT，ERK和NF-кB等通路，抑制恶性B淋巴细胞的凋亡，导致后者的异常增殖。除此以外，在RA、MS、SLE等多种自身免疫性疾病中，BTK介导与疾病密切相关的病生理过程，包括产生自身抗体、分泌多种促炎因子。 BTK相关信号通路目前在研的BTK抑制剂主要有三代，分别是：第一代：伊布替尼为全球首个获批的BTK抑制剂，适应症覆盖最多；第二代：阿卡替尼、泽布替尼、奥布替尼等第二代抑制剂，着力提高药物靶向性及安全性。其中泽布替尼的适应症覆盖较全，阿卡替尼仅覆盖部分核心适应症；第三代：以Pirtobrutinib为代表，系采用新的结合位点的非共价抑制剂。从全球范围来看，近年来BTK抑制剂整体市场稳健增长。2022年五款BTK抑制剂合计销售收入111亿美元，同比增长8.6%。从PDB样本医院销售数据来看，我国BTK抑制剂市场较快增长。2022年PDB样本医院销售额为5亿元，2018-2022年PDB样本医院BTK抑制剂销售收入年均复合增速为132%。激酶小分子抑制剂经过一段时间治疗后，往往会产生耐药突变。为了克服新的耐药突变，BTK降解剂策略成为下一代BTK药物开发的选择。据不完全统计，目前在研的BTK降解剂约二十余种。关于Nurix Nurix 成立于2009年，拥有独特的DELigase 靶向蛋白调节平台；DELigase 平台具有高度差异化，能够识别可以降低靶向蛋白质降解（TPD）或增加（TPE）蛋白质水平的小分子，也称之为靶向蛋白质调节（TPM）的过程。基于该平台，Nurix 既可以利用E3 连接酶降解特定的靶蛋白（如BTK CTM），也可以抑制特定连接酶以提高底物蛋白水平（如CBL-B 抑制剂）。公司专注于开发肿瘤学、免疫肿瘤学、过继细胞治疗和免疫疾病领域药物，正在推进多个内部发现和全资拥有的临床阶段候选药物，旨在治疗血液系统恶性肿瘤和实体瘤患者。本次会议中，公司重点披露的数据还包括一款NX-2127，可降解BTK、Ikaros（IKZF1）和Aiolos（IKZF3）的新型双功能分子，目前正在对患有复发或难治性 B 细胞恶性肿瘤的成年人进行 1a/b 期临床试验评估，数据显示：采用NX-2127 治疗的 CLL 细胞具有明显的免疫调节作用，包括上调干扰素 (IFN) 反应基因 CD38、增强免疫反应、促进 T 细胞向 TH1 表型分化、增强抗肿瘤免疫力、减少 Treg 分化（支持向免疫抑制程度较低的微环境转变并增强免疫突触形成）和 T 细胞介导的细胞毒性。此外，RNA测序揭示了NX-2127处理的CLL细胞中独特的基因表达模式，区分了应答者和无应答者，并进一步证明了其独特的T细胞调节作用。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

临床结果临床1期临床2期蛋白降解靶向嵌合体

2024-12-02

·GlobeNewswire-Health Care

Nurix Therapeutics Announces Webcast To Review New Data from Its Phase 1 Clinical Trial of BTK Degrader NX-5948 Presented at the 66th American Society of Hematology (ASH) Annual Meeting

SAN FRANCISCO, Dec. 02, 2024 (GLOBE NEWSWIRE) -- Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical stage biopharmaceutical company developing targeted protein modulation drugs designed to treat patients with cancer and inflammatory diseases, today announced that the company will host a live webcast to review new clinical data from the ongoing Phase 1a/1b clinical trial of its Bruton’s tyrosine kinase (BTK) degrader program NX-5948, and provide a corporate update, at 8:15 p.m. PT (11:15 p.m. ET) on Monday, December 9, 2024. The webcast will feature a presentation by guest speaker and clinical study investigator Nirav N. Shah, M.D., M.S.H.P., Associate Professor of Medicine, Division of Hematology and Oncology at the Medical College of Wisconsin, who will present clinical data from the ongoing Phase 1a/1b trial of NX-5948 in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). Arthur T. Sands, M.D., Ph.D., Nurix’s president and chief executive officer, Paula G. O’Connor, M.D., Nurix’s chief medical officer, and Gwenn M. Hansen, Ph.D., Nurix’s chief scientific officer, will outline Nurix’s clinical development strategy for NX-5948 in both oncology and autoimmune indications and provide an overview of Nurix’s other clinical stage programs. Webcast detailsDate and time: Monday, December 9, 2024, 8:15 p.m. PT (11:15 p.m. ET) Access Details: The live webcast and subsequent archived replay will be available in the Investors section of the Nurix website under Events and Presentations. About NX-5948 NX-5948 is an investigational, orally bioavailable, brain penetrant, small molecule degrader of BTK. NX-5948 is designed to specifically eliminate BTK, a key growth signaling protein in B cells, through degradation by the ubiquitin proteasome system of the cell. NX-5948 is currently being evaluated in a Phase 1 clinical trial in patients with relapsed or refractory B cell malignancies. Nurix has previously reported that NX-5948 is highly potent against a range of tumor cell lines that are resistant to current BTK inhibitor therapies, an important consideration in heavily pretreated CLL/SLL patient populations. Additional information on the ongoing clinical trial can be accessed at clinicaltrials.gov (NCT05131022). About Nurix Therapeutics, Inc.Nurix Therapeutics is a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of innovative small molecules and antibody therapies based on the modulation of cellular protein levels as a novel treatment approach for cancer, inflammatory conditions, and other challenging diseases. Leveraging extensive expertise in E3 ligases together with proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform, to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin-proteasome system to selectively decrease or increase cellular protein levels. Nurix’s wholly owned, clinical stage pipeline includes targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene B, an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells. Nurix is headquartered in San Francisco, California. For additional information visit http://www.nurixtx.com. Forward-Looking StatementsThis press release contains statements that relate to future events and expectations and as such constitute forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. When or if used in this press release, the words “anticipate,” “believe,” “could,” “estimate,” “expect,” “intend,” “may,” “outlook,” “plan,” “predict,” “should,” “will,” and similar expressions and their variants, as they relate to Nurix, may identify forward-looking statements. All statements that reflect Nurix’s expectations, assumptions or projections about the future, other than statements of historical fact, are forward-looking statements, including, without limitation, statements regarding the planned timing for the provision of updates and findings from Nurix’s clinical trials. Forward-looking statements reflect Nurix’s current beliefs, expectations, and assumptions regarding the future of Nurix’s business, its preclinical and clinical results, future conditions and other factors Nurix believes are appropriate in the circumstances. Although Nurix believes the expectations and assumptions reflected in such forward-looking statements are reasonable, Nurix can give no assurance that they will prove to be correct. Forward-looking statements are not guarantees of future performance and are subject to risks, uncertainties and changes in circumstances that are difficult to predict, which could cause Nurix’s actual activities and results to differ materially from those expressed in any forward-looking statement. Such risks and uncertainties include, but are not limited to: (i) the timing and results of Nurix’s clinical trials; (ii) the impact of macroeconomic conditions and global events on Nurix’s business, clinical trials and financial condition; and (iii) other risks and uncertainties described under the heading “Risk Factors” in Nurix’s Quarterly Report on Form 10-Q for the fiscal quarter ended August 31, 2024, and other SEC filings. Accordingly, readers are cautioned not to place undue reliance on these forward-looking statements. The statements in this press release speak only as of the date of this press release, even if subsequently made available by Nurix on its website or otherwise. Nurix disclaims any intention or obligation to update publicly any forward-looking statements, whether in response to new information, future events, or otherwise, except as required by applicable law. Contacts: InvestorsJason Kantor, Ph.D.Nurix Therapeuticsir@nurixtx.com Elizabeth Wolffe, Ph.D.Wheelhouse Life Science Advisorslwolffe@wheelhouselsa.com MediaAljanae ReynoldsWheelhouse Life Science Advisorsareynolds@wheelhouselsa.com

临床1期

100 项与 NX-5948 相关的药物交易

登录后查看更多信息

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
慢性淋巴细胞白血病	临床1期	美国	Nurix Therapeutics, Inc.	2022-04-13
慢性淋巴细胞白血病	临床1期	荷兰	Nurix Therapeutics, Inc.	2022-04-13
慢性淋巴细胞白血病	临床1期	英国	Nurix Therapeutics, Inc.	2022-04-13
弥漫性大B细胞淋巴瘤	临床1期	美国	Nurix Therapeutics, Inc.	2022-04-13
弥漫性大B细胞淋巴瘤	临床1期	荷兰	Nurix Therapeutics, Inc.	2022-04-13
弥漫性大B细胞淋巴瘤	临床1期	英国	Nurix Therapeutics, Inc.	2022-04-13
滤泡性淋巴瘤	临床1期	美国	Nurix Therapeutics, Inc.	2022-04-13
滤泡性淋巴瘤	临床1期	荷兰	Nurix Therapeutics, Inc.	2022-04-13
滤泡性淋巴瘤	临床1期	英国	Nurix Therapeutics, Inc.	2022-04-13
套细胞淋巴瘤	临床1期	美国	Nurix Therapeutics, Inc.	2022-04-13

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


NCT05131022 (NX-5948-301, ASH2024) 人工标引	临床1期	慢性淋巴细胞白血病末线 \| 三线	34	NX-5948	夢範糧夢構蓋選蓋鏇繭(鏇淵願鹽構構襯繭網願) = Most common TEAEs were: purpura/contusion (44.1%, no Gr≥3); thrombocytopenia (23.5%, 2.9% Gr≥3); petechiae (29.4%, no Gr≥3); fatigue (20.6%, no Gr≥3); neutropenia (17.6%, 14.7% Gr≥3; pts with up to Gr 4 cytopenias were eligible for study participation); rash (23.5%, no Gr≥3, 2.9% SAE); headache (23.5%, no Gr≥3).There was no new onset atrial fibrillation/flutter or hypertension. 齋膚廠壓選鹽餘網醖繭 (鏇憲選夢遞醖鑰鹹襯積 ) 更多	积极	2024-12-09
NCT05131022 (GlobeNewswire) 人工标引	临床1期	巨球蛋白血症	79	NX-5948	廠觸鹹衊鬱製顧齋繭簾(鑰淵鏇膚齋範選網齋夢) = 簾膚夢鹽構餘鹹艱窪構鹽顧積齋範選鹹構觸壓 (夢壓廠憲廠艱選選鬱淵 ) 更多	积极	2024-10-19
NCT05131022 (EHA2024) 人工标引	临床1期	慢性淋巴细胞白血病 \| B细胞恶性肿瘤	46	NX-5948	簾構構構範壓積獵築襯(壓醖繭餘觸範衊蓋糧壓) = none 壓簾鏇壓鑰壓夢膚壓範 (鹹衊鬱網鑰餘鑰醖憲憲 ) 更多	积极	2024-05-14
NCT05131022 (Biospace) 人工标引	临床1期	慢性淋巴细胞白血病	7	NX-5948	齋網鏇窪築鏇願鑰製鏇(繭範淵構廠製壓構選窪) = 鏇築醖鹹壓餘選積鹹鏇鹹觸窪醖醖廠網餘構遞 (獵遞網觸淵餘餘窪鏇網 ) 更多	积极	2024-01-16
NCT05131022 (NX-5948-301, ASH2023) 人工标引	临床1期	B细胞淋巴瘤三线	14	NX-5948	鏇獵範積餘廠蓋積築齋(衊淵夢獵夢積糧膚壓窪) = 壓遞網鹽鏇壓鹽獵衊繭獵繭構艱壓鏇蓋艱繭蓋 (築顧鹹襯襯簾鏇鑰艱遞 ) 更多	积极	2023-12-11