A Phase IIa, Open-label Study to Evaluate the Safety, Pharmacokinetics and Preliminary Efficacy of Camizestrant in Combination With Atirmociclib in Participants With ER-positive, HER2-negative Advanced Breast Cancer (SERENA-1b)

A study to investigate camizestrant in combination with atirmociclib in participants with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer previously treated with a cyclin dependent kinase 4/6 (CDK4/6) inhibitor.

开始日期2026-04-10

申办/合作机构

AstraZeneca PLC

NCT07215078

/ Recruiting临床1期

A PHASE 1, OPEN-LABEL, TWO-PERIOD, CROSS-OVER STUDY TO EVALUATE DOSE PROPORTIONALITY OF ATIRMOCICLIB (PF-07220060) PHARMACOKINETICS WHEN ADMINISTERED UNDER FED CONDITIONS TO HEALTHY PARTICIPANTS

The purpose of this clinical trial is to learn about the dose proportionality on the PK of the study medicine (called atirmociclib) when administered in the various doses range under the fed condition in healthy participants.
This study is seeking participants who are:
1. male and female aged 18 to 65 years are healthy as determined by medical evaluation including medical history, physical examination, and laboratory tests
2. with BMI of 17.5-30.5 kg/m2; and a total body weight >50 kgs (110 lbs.).
All participants (72 total) in this study will receive atirmociclib at Dose (A), Dose (B), Dose (C), and Dose (D) oral dose in 1 of the 12 treatment sequences among 6 cohorts under fed conditions.
Atirmociclib will be given by mouth at the study research unit once single dose about 30 minutes after a moderate fat standard calorie meal.
Dose proportionality will be evaluated on the pharmacokinetics (PK), safety and tolerability of atirmociclib at Doses (A), (B), (C), and (D) oral dose under the fed condition.
Including the 28 days of screening window and the 35 days safety follow-up period, the total study duration for each participant can be up to 71 days, containing 2 periods (6 days for each period), minimum 7-day interval between two periods, and follow-up period 28 to 35 days from administration of the final dose of study intervention. During this time, they will undergo safety laboratory and serial blood PK samplings up to 120 hours after administration of atirmociclib to determine plasma concentrations of atirmociclib. Participants will be discharged from the research unit on Period 2 Day 6 following completion of all assessments.

开始日期2025-10-08

申办/合作机构

Pfizer Inc.

NCT07160738

/ Completed临床1期

AN INTERVENTIONAL, PHASE 1, OPEN-LABEL, TWO-COHORT, TWO-PERIOD, FIXED SEQUENCE STUDY TO ESTIMATE THE EFFECT OF MULTIPLE DOSES OF ITRACONAZOLE AND PROBENECID ON THE PHARMACOKINETICS OF SINGLE DOSE PF-07220060 ADMINISTERED UNDER THE FED CONDITION TO HEALTHY PARTICIPANTS

The purpose of the study is to see and learn the effect of multiple doses of a strong CYP3A4 inhibitor and a potent UGT2B7 inhibitor on the PK of PF-07220060.

开始日期2025-09-22

申办/合作机构

Pfizer Inc.

100 项与 Atirmociclib 相关的临床结果

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100 项与 Atirmociclib 相关的转化医学

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100 项与 Atirmociclib 相关的专利（医药）

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项与 Atirmociclib 相关的文献（医药）

2026-05-01·JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES

Identification and characterization of atirmociclib metabolites through high resolution-mass spectrometry-based in vitro and in vivo rat biological sample analysis

Article

作者: Nandi, Sukhendu ; Pawar, Swati Ramesh ; Loganathan, Gayathri ; Srikanth, Pirangi ; Kumar, Deepak ; Biradar, Rushikesh ; Shaik, Khaja Moinuddin

Cancer continues to be one of the foremost causes of global morbidity and mortality, underscoring the urgent need for innovative therapeutic agents. Atirmociclib, a selective cyclin-dependent kinase 4 (CDK4) inhibitor, is currently being explored for its remarkable anticancer potential. Although its pharmacological profile is promising, there remains a scarcity of data regarding its metabolic pathway. This study seeks to provide a detailed characterization of the in vitro and in vivo metabolism of atirmociclib, utilizing human liver microsomes (HLM), rat liver microsomes (RLM), and HS9 fractions, alongside female Sprague-Dawley rats as the in vivo model. Employing high-resolution LC-ESI-Q-TOF-MS/MS for metabolite profiling in rat plasma, urine, and feces, we identified and structurally elucidated a total of seven novel phase I and phase II metabolites based on accurate mass measurements and their fragmentation patterns. Notable biotransformation pathways include N-dealkylation, hydroxylation, oxidation, dihydroxylation, sulfate conjugation, and glucuronidation. In silico toxicity predictions classified atirmociclib and its metabolites within class 4 (predicted LD₅₀: 1000-2000 mg/kg), suggesting low acute toxicity while highlighting potential risks such as neurotoxicity, respiratory toxicity, and immunogenicity. This research article is the first time to discuss the complete metabolite profiling including identification and characterization of atirmociclib metabolites as well as its biotransformation mechanism. ABBREVATIONS.

2025-12-25·JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Atirmociclib (PF-07220060): A Potent and Selective CDK4 Inhibitor

Article

作者: Kania, Robert ; Boras, Britton ; Kath, John C. ; Cianfrogna, Julie A. ; Wei, Na ; Ninkovic, Sacha ; Deal, Judith G. ; Gallego, Gary M. ; Dress, Klaus ; Lafontaine, Jennifer ; Shen, Hong ; Cho-Schultz, Sujin ; Pascual, Bernadette ; Johnson, Eric ; Marroquin, Lisa ; Cox, Loretta ; Orr, Suvi ; Quinlan, Casey ; Anders, Lars ; Sach, Neal ; Edwards, Martin ; Jalaie, Mehran ; Cao, Fengjuan ; Petroski, Matthew ; Bernier, Louise ; Palmer, Cynthia ; Chen, Ping ; Sacaan, Aida ; Nair, Sajiv K.

Inhibitors of cyclin-dependent kinases 4 and 6 have been shown to be clinically effective for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced, or metastatic breast cancer. These agents, however, often show neutropenia, likely due to the role of CDK6 in hematopoiesis. Herein described is the discovery of a series of aminopyrimidine-based selective CDK4 inhibitors. Central to our strategy were efficiency-based optimization (LipE and LipMetE), structure-based drug design, and molecular dynamics simulation. The culmination of these efforts resulted in the discovery of PF-07220060 (atirmociclib), which possessed high potency and levels of selectivity for CDK4 over CDK6 that translated to minimal impact on neutrophils while driving efficacy in a mouse ZR75-1 xenograft model.

2025-10-01·JOURNAL OF MOLECULAR BIOLOGY

Distinct Allosteric Networks in CDK4 and CDK6 in the Cell Cycle and in Drug Resistance

Article

作者: Kõivomägi, Mardo ; Nussinov, Ruth ; Liu, Yonglan ; Heidebrink, Gretchen ; Bradburn, Devin ; Jang, Hyunbum ; Zhang, Wengang

Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) are key regulators of the G₁-S phase transition in the cell cycle. In cancer cells, CDK6 overexpression often outcompetes CDK4 in driving cell cycle progression, contributing to resistance against CDK4/6 inhibitors (CDK4/6i). This suggests distinct functional and conformational differences between these two kinases, despite their striking structural and sequence similarities. Understanding the mechanisms that differentiate CDK4 and CDK6 is crucial, as resistance to CDK4/6i-frequently linked to CDK6 overexpression-remains a significant therapeutic challenge. Notably, CDK6 is often upregulated in CDK4/6i-resistant cancers and rapidly proliferating hematopoietic stem cells, underscoring its unique regulatory roles. We hypothesize that their distinct conformational dynamics explain their differences in phosphorylation of retinoblastoma protein, Rb, inhibitor efficacy, and cell cycle control. This leads us to question how their dissimilar conformational dynamics encode their distinct actions. To elucidate their differential activities, molecular mechanisms, and inhibitor binding, we combine biochemical assays and molecular dynamics (MD) simulations. We discover that CDK4 and CDK6 have distinct allosteric networks connecting the β3-αC loop and the G-loop. CDK6 exhibits stronger coupling and shorter path lengths between these regions, resulting in higher kinase activity upon cyclin binding and impacting inhibitor specificity. We also discover an unrecognized role of the unstructured CDK6 C-terminus, which allosterically connects and stabilizes the R-spine, facilitating slightly higher activity. Our findings bridge the gap between the structural similarity and functional divergence of CDK4 and CDK6, advancing the understanding of kinase regulation in cancer biology.

157

项与 Atirmociclib 相关的新闻（医药）

2026-05-23

·吉林玖禄健康咨询平台

纯干货！2026乳腺癌治疗重磅更新！五种新药详解！！！

2026乳腺癌治疗重磅更新！ 5款新药详解（成分+疗效）全分型都有新希望前言对于乳腺癌患者而言，每一款新药的问世，都意味着多一份生存的希望。2026年第一季度，乳腺癌领域多项临床研究公布关键成果，针对三阴性*、HER2阳性*、HR+/HER2-*三大主流分型，多款新药突破治疗瓶颈，即便晚期、多线耐药患者，也迎来了全新治疗选择。本文用通俗易懂的语言，详细拆解每款药物的核心成分、作用原理、临床疗效，没有专业门槛，患者和家属都能轻松看懂！科普医师简介三级主任医师，吉林省卫计委拔尖创新人才；国家淋巴瘤质控专家委员会委员，中国医药教育协会淋巴瘤分会主任委员，CSCO淋巴瘤专家委员会常委，中国女医师协会靶向治疗专业委员会副主任委员。以医者初心，做有温度的肿瘤科普，拆解难懂医学、聚焦肿瘤前沿、讲解规范用药、分享饮食调养。传递专业靠谱的肿瘤知识，用专业守护健康，用温暖陪伴患者，让家属从容面对，科学抗癌，温柔同行。三阴性乳腺癌：攻克难治分型，两大新药带来突破三阴性乳腺癌因缺乏有效治疗靶点，一直是乳腺癌中最难治、复发风险最高的分型，今年两款新药直接破解这一难题。 1. Paxalisib（GDC-0084）* ✅ 药物成分：口服小分子化合物，化学式为C₁₈H₂₂N₈O₂，属于PI3K/AKT/mTOR通路特异性抑制剂*。 ✅ 作用原理：精准阻断癌细胞生长的关键信号通路，切断肿瘤的营养供给，抑制癌细胞增殖、转移，同时可穿透血脑屏障，对乳腺癌脑转移也有潜在治疗效果。 ✅ 临床疗效：联合免疫治疗+化疗，用于晚期三阴性乳腺癌，内脏转移患者中超6成病情缓解，平均疗效持续时间达6.1个月，不良反应以轻中度为主，患者耐受性更好。 2. INT230-6* ✅ 药物成分：复方制剂，核心包含顺铂+硫酸长春碱两种化疗成分，搭配专用渗透增强剂SHAO。 ✅ 作用原理：借助渗透增强剂，让化疗药物精准扩散至整个肿瘤组织，局部杀灭癌细胞的同时，激活全身免疫系统，让免疫细胞主动攻击远处转移病灶。 ✅ 临床疗效：用于早期三阴性乳腺癌新辅助治疗，病理完全缓解率（pCR）高达71.4%，是传统方案的2倍多，且严重不良反应减少44%，在提升疗效的同时，大幅降低治疗副作用。 HER2阳性乳腺癌：双药联合，逆转多线耐药 HER2阳性乳腺癌癌细胞侵袭性强，容易出现耐药情况，此次双靶向+免疫全新组合，为耐药患者打开新治疗窗口。 1. Zanidatamab（泽尼达妥单抗） ✅ 药物成分：人源化IgG1型HER2双特异性抗体。 ✅ 作用原理：同时结合HER2蛋白的两个不同位点，加速HER2蛋白降解，阻断癌细胞信号传导，同时触发三重免疫杀伤作用，精准消灭HER2阳性癌细胞。 ✅ 临床疗效：多线治疗失败的晚期HER2阳性乳腺癌患者，联合用药后客观缓解率达55.6%，疾病控制率超7成。 2. Evorpacept（ALX148）* ✅ 药物成分：CD47-SIRPα阻断融合蛋白，由SIRPα胞外区+改造IgG1-Fc段组成。 ✅ 作用原理：阻断癌细胞发出的“别吃我”信号，激活体内巨噬细胞，主动吞噬、清除癌细胞，与泽尼达妥单抗联合，实现1+1＞2的抗癌效果。 ✅ 临床疗效：尤其对CD47高表达的患者，治疗获益更显著，有效解决HER2阳性晚期患者耐药后无药可用的困境。 HR+/HER2-乳腺癌：破解耐药难题，新一代抑制剂问世 HR+/HER2-是乳腺癌最常见分型，CDK4/6抑制剂耐药后，患者一直缺少高效治疗方案，新一代靶向药成功破局。 Atirmociclib（PF-07220060） ✅ 药物成分：口服高选择性小分子CDK4激酶抑制剂，化学式为C₂₂H₂₇ClFN₅O₃。 ✅ 作用原理：精准抑制CDK4靶点，对CDK6选择性高出20倍以上，只阻断癌细胞分裂，不影响正常造血功能，大幅降低传统抑制剂的骨髓毒性。 ✅ 临床疗效：用于CDK4/6抑制剂耐药后的HR+/HER2-晚期乳腺癌患者，可将疾病进展、死亡风险降低40%，各年龄段、各分期患者均能获益，安全性更优。名词释义 1. Paxalisib（GDC-0084）帕沙利西布，由基因泰克原研、可透过血脑屏障的口服 PI3K/mTOR 双重抑制剂。靶点：强效抑制 I 类 PI3K（α/δ/γ/β）及 mTOR。适应症：胶质母细胞瘤（脑胶质瘤），获 FDA 孤儿药、快速通道资格。特点：高脑渗透率，阻断肿瘤增殖关键通路。 2.PI3K/AKT/mTOR 通路特异性抑制剂靶向 PI3K/AKT/mTOR 信号轴的小分子 / 生物药，该通路在肿瘤中高频激活，调控细胞增殖、存活、代谢及血管生成。 PI3K：磷脂酰肌醇 3 - 激酶，催化 PIP2 生成 PIP3。 AKT：蛋白激酶 B，PIP3 激活后介导下游信号。 mTOR：哺乳动物雷帕霉素靶蛋白，调控蛋白合成与细胞生长。 3. INT230-6 瘤内注射型复方抗癌制剂，由 Intensity Therapeutics 开发，基于 DfuseRxSM 技术平台。成分：顺铂 + 长春花碱 + 渗透增强剂 SHAO。机制：直接瘤内给药，高效扩散并杀伤癌细胞；诱导免疫原性细胞死亡，激活全身抗肿瘤免疫。适应症：三阴性乳腺癌、肉瘤等实体瘤，获 FDA 快速通道资格。 4. Evorpacept（ALX148）伊沃帕赛普，ALX Oncology 开发的SIRPα-Fc 融合蛋白类 CD47 抑制剂。靶点：高亲和力结合肿瘤细胞表面CD47，阻断 CD47-SIRPα“别吃我” 信号，恢复巨噬细胞吞噬功能ALX Oncology。结构：灭活 Fc 段，避免血液毒性（如贫血、血小板减少）。适应症：HER2 阳性胃癌、乳腺癌、头颈癌等实体瘤，II/III 期临床中。 5. Atirmociclib（PF-07220060）阿替莫西利，辉瑞开发的新一代高选择性 CDK4 抑制剂。靶点：选择性抑制 CDK4（CDK4/CDK6 选择性≈33 倍），对 CDK6 影响极小。机制：阻断 CDK4 / 周期蛋白 D 复合物，阻滞细胞周期 G1 期，抑制肿瘤增殖。优势：降低 CDK6 相关中性粒细胞减少风险，安全性更优。适应症：HR+/HER2 - 晚期乳腺癌，用于既往 CDK4/6 抑制剂进展后治疗。 6.三阴性*、HER2阳性*、HR+/HER2-* 这三类是乳腺癌最核心的分子分型，由病理免疫组化（ER、PR、HER2）结果定义，直接决定治疗方案与预后。一、HR+/HER2-（激素受体阳性、HER2 阴性）定义：ER 阳性（≥1%）、PR 阳性、HER2 阴性（IHC 0/1 + 或 FISH 阴性）。别名：Luminal A 型（Ki-67 低，＜14%），最常见亚型。占比：约70%，最常见。特点：生长慢、恶性度低、复发风险低。治疗：以内分泌治疗为主（如他莫昔芬、芳香化酶抑制剂），早期常不需化疗。预后：最好，早期 5 年生存率＞90%。二、HER2 阳性（HER2+，HR 可阳 / 阴）定义：HER2 阳性（IHC 3 + 或 FISH 扩增），ER/PR 可阳可阴。亚型：HER2 阳性型（HR-）：ER-、PR-、HER2+，占 15%–20%。 Luminal B 型（HER2+）：ER+、PR+、HER2+，占 5%–10%。特点：癌细胞增殖快、侵袭性强，易早期复发（1–3 年）。治疗：抗 HER2 靶向治疗（曲妥珠单抗、帕妥珠单抗等）+ 化疗 ± 内分泌治疗。预后：靶向药问世后显著改善，早期 5 年生存率＞75%。三、三阴性（TNBC，HR-/HER2-）定义：ER 阴性、PR 阴性、HER2 阴性，三项全阴。占比：10%–20%，多见于年轻女性（＜40 岁）。特点：增殖极快、侵袭性最强，易内脏 / 脑转移，复发率高。治疗：传统以化疗为主；BRCA 突变可用 PARP 抑制剂，PD-L1 阳性可联合免疫治疗。预后：最差，缺乏精准靶点，晚期 5 年生存率约 15%。医生温馨提示 1. 上述药物目前多处于Ⅰ/Ⅱ期临床研究阶段，尚未在国内全面获批上市，符合条件的患者可优先参与临床试验。 2. 新药治疗均需精准匹配靶点，用药前建议完善基因检测、蛋白表达检测（如PI3K、HER2、CD47等），避免盲目用药。 3. 新药治疗方案需由专业肿瘤医生评估后制定，患者切勿自行参考用药，治疗期间需严格监测不良反应。乳腺癌治疗早已进入精准化时代，新药不断迭代，难治分型、耐药患者都有了新的生存机会。我们也会持续关注最新研究进展，第一时间为大家分享实用、靠谱的抗癌资讯，愿每一位患者都能找到适合自己的治疗方案，向阳而生！免责声明：本文仅为医疗科普，不替代专业医生诊断与治疗建议，具体治疗方案请遵医嘱。点击关注作者更多精彩内容合集：乳腺癌科普合集☜ 合集：胃癌&肠癌科普合集☜ 合集：肺癌科普合集☜ 合集：淋巴瘤科普合集☜ 合集：指南共识☜ 如果您喜欢鲍医生的医疗科普内容请关注我们给我们一点支持~ 吉林玖禄健康咨询平台科普说明本文为健康科普，不替代个体化诊疗方案具体用药与治疗请遵医嘱

2026-05-23

·嘉华药锐DeepKinase

ASCO 2026 PROTAC专题：9项核心研究全景盘点，临床兑现进入关键阶段

ASCO 2026 开幕进入倒计时作为全球肿瘤领域最具影响力的学术盛会之一，ASCO每年发布的研究成果都代表着肿瘤治疗的发展前沿。其中，蛋白水解靶向嵌合体（PROTAC）作为靶向蛋白降解（Targeted Protein Degradation, TPD）领域最受关注的技术路线之一，凭借突破传统“小分子不可成药”限制及潜在克服耐药性的优势，正在加速从概念验证走向临床兑现。我们基于 ASCO 2026 已公开摘要，系统梳理 PROTAC 相关研究进，筛选出9项核心项目，一个信号非常明确： PROTAC 已不再是“未来技术”，而正在进入真正的临床竞争阶段。 01 1个关键数据：近九成研究已进入临床阶段本届ASCO PROTAC 相关研究中： • 临床阶段项目：8 项（88.9%） • 临床前/机制研究：1 项（11.1%）这意味着什么？过去几年，行业关注重点还是“PROTAC 能不能做”。而现在，问题已经变成：“谁能更快做出真正有效、真正可商业化的产品”。 TPD 正在进入临床兑现关键窗口期。 02 3个趋势，正在定义PROTAC 下一阶段竞争格局趋势1：技术边界持续拓宽除了经典小分子PROTAC 外，今年还出现新的探索方向： • 放射性核素结合策略 • 多模式联合设计 • 新型递送体系探索蛋白降解技术生态正从单一工具演变为多路径创新平台。趋势2：联合治疗成为核心策略超过半数研究涉及 PROTAC 与其他疗法联合应用，包括： · CDK4/6 抑制剂 · 内分泌治疗 · 化疗 · 其他靶向治疗原因并不复杂。单一治疗模式往往面临耐药挑战，而PROTAC 的蛋白降解机制正在成为突破耐药的重要工具。未来竞争，不只是“谁能降解”，而是谁能形成更优治疗组合。趋势3：临床转化明显提速从今年数据看，PROTAC 已逐步摆脱“长期停留临床前”的标签。越来越多项目进入 I/II 期临床验证。行业正在从“证明机制成立”，进入“证明临床价值成立”。 03 热门靶点：PROTAC 正在突破传统边界从靶点布局来看，核受体仍是核心方向。重点包括： ER（雌激素受体） AR（雄激素受体） PSMA（前列腺特异性膜抗原）但更值得关注的是：BCL6、BTK、EGFR 等新方向持续出现。这意味着 PROTAC 正在逐步突破传统核受体边界，向更多“难成药靶点”延伸。过去做不到的，不代表未来做不到。这正是蛋白降解技术真正吸引行业持续投入的原因。 04 哪些疾病领域最热？从适应症布局看：前列腺癌成为核心方向。其中，去势抵抗性前列腺癌（CRPC）相关研究达到 3 项。与此同时： • HR 阳性乳腺癌 • 非霍奇金淋巴瘤 • 弥漫性大 B 细胞淋巴瘤（DLBCL） • 套细胞淋巴瘤（MCL） • 非小细胞肺癌（NSCLC）等方向均已有布局。一个趋势越来越明显： PROTAC 正在从血液瘤逐步走向实体瘤主战场。 05 值得关注的代表项目 ARV-393 Arvinas 开发的 BCL6 靶向 PROTAC 降解剂，本次公布了针对晚期非霍奇金淋巴瘤的 I 期临床数据，进一步验证 BCL6 降解策略的治疗潜力。 Vepdegestrant 领先的ER 靶向 PROTAC 降解剂，本次发布了联合阿贝西利（Abemaciclib）及 Atirmociclib 治疗 HR 阳性乳腺癌的临床研究结果，持续推进乳腺癌领域临床布局。 AZD9750 AstraZeneca 研发的AR 靶向 PROTAC 候选药物，公布了单药及联合治疗去势抵抗性前列腺癌的 I/II 期数据，聚焦去势抵抗性前列腺癌治疗。 HJ-004-02 中国企业研发的EGFR 靶向 PROTAC，本次发布了非小细胞肺癌相关临床数据，标志着中国创新力量在 PROTAC 赛道持续突破。 DS-9051b Daiichi Sankyo 开发的BTK 靶向 PROTAC，用于套细胞淋巴瘤治疗，进一步拓展 PROTAC 在血液瘤领域的应用边界。 06 研发格局：全球头部机构深度布局本次研究背后汇聚了全球领先的科研机构与药企，包括： · Memorial Sloan Kettering Cancer Center（3项） · Stanford University School of Medicine（3项） · Pfizer（2项） · Arvinas（2项）与此同时，北京肿瘤医院、上海辐联医药等中国机构也持续参与全球创新竞争，中国在 PROTAC 领域的话语权正不断增强。 07 PROTAC 热潮背后：研发挑战正在升级随着PROTAC 临床开发不断推进，行业关注重点也在发生变化：如何精准评估降解效率？如何识别潜在脱靶效应？如何建立药效评价体系？如何寻找耐药机制与伴随标志物？功能蛋白质组学正在成为解决这些问题的重要基础工具。 08 嘉华药锐：功能蛋白质组学赋能 TPD 研发随着 PROTAC 药物研发进入临床转化关键阶段，如何精准解析降解机制、验证靶点占领、评估药效并发现潜在耐药机制，正成为推动 TPD 成功开发的核心挑战。嘉华药锐DeepKinase依托自主研发的功能蛋白质组学平台与 AI 虚拟细胞平台 CellProteo®，为 PROTAC 及更广泛的靶向蛋白降解（TPD）药物研发提供全流程解决方案。 DoTD®：面向降解剂研发的功能蛋白质组学平台聚焦 PROTAC、分子胶等降解剂开发需求，可支持：靶蛋白降解效率精准定量全蛋白组脱靶谱分析降解选择性与泛素化机制解析耐药机制发现与生物标志物筛选 QSure®：临床蛋白质组检测平台支持临床样本药效验证与伴随标志物开发，加速从机制研究到临床转化。 CellProteo®：AI虚拟细胞平台通过整合动态蛋白质组数据、空间组学结构数据及先验知识库，构建高保真细胞模拟系统，助力： PROTAC作用机制模拟降解网络动态预测联合用药方案优化新型降解靶点发现从靶点验证到临床转化，嘉华药锐正通过“蛋白质组学 + AI”双引擎，持续推动靶向蛋白降解药物研发迈向更高效率与更高成功率。嘉华药锐DeepKinase 嘉华药锐DeepKinase，品牌“旦白志”，是一家AI+蛋白质组学技术平台公司，专注于精准医疗并助力新药研发。公司由高层次科学家、产业专家和成功创业者创立，凭借自主知识产权的前沿蛋白质组学技术，已实现深度靶向蛋白质组学技术的产品化，与多家头部医院和企业建立了合作伙伴关系，覆盖京津冀、长三角及北美市场，并已完成多轮数亿元融资。在AI技术的驱动下，嘉华药锐结合质谱测定的大量蛋白基础数据与AI大语言模型的应用场景，进一步提升了蛋白质组学分析的精准度与效率，建立了包括激酶抑制剂（TKI）和PROTAC药物靶向降解在内的多个分析平台，将AI+蛋白质组学在新药开发领域的应用推向深水区。如果把疾病比作黑箱，嘉华药锐则致力于用AI结合公司蛋白质组学核心专利技术，在黑箱中点亮探照灯，通过加深人类对于疾病和健康的理解，并全力拓展AI+蛋白质组学的更广阔应用空间，真正推动精准医疗走入下一个时代。

2026-05-22

·EndPoints

Ibrance's would-be successors, the data that helped sell Tubulis to Gilead, and more at ASCO

All of the regular ASCO abstracts dropped Thursday afternoon, with the biggest news coming from the VEGF bispecific race , Merck and Kelun-Biotech’s TROP2 ADC known as sac-TMT, and multiple head and neck cancer updates . But there were plenty of other developments across cancer trials and new mechanisms, and we’ve rounded up the best of the rest here. Find updates below on potential successors for Pfizer’s blockbuster Ibrance, the Tubulis data that got Gilead Sciences excited enough to buy it out, and more. Both Pfizer and BeOne Medicines (formerly BeiGene) are developing CDK4 inhibitors in a bid to take up Ibrance’s mantle in breast cancer, as the first Ibrance biosimilars are expected as soon as next year. For Pfizer, the successor is called atirmociclib. The drugmaker toplined a separate Phase 2 success earlier this year in HR-positive, HER2-negative breast cancer, but an abstract released Thursday supplemented those results. Patients received either a combination of atirmociclib and an aromatase inhibitor called letrozole, or letrozole alone. Efficacy was measured with an endpoint called “complete cell cycle arrest,” or CCCA, which examines how quickly patients’ tumor cells stopped dividing. After 14 days, 45 of 51 patients (88.2%) who took the combination regimen saw their cell division slow by a meaningful amount, compared to 10 of 56 (17.9%) who only received letrozole. The data come from patients with advanced breast cancer who progressed after treatment with a CDK4/6 inhibitor (including Ibrance). Pfizer enrolled patients whose tumor cells were dividing rapidly. BeOne, meanwhile, is researching a program called BGB-43395 and reported data from a safety expansion cohort of a Phase 2 study, also looking at a combination with letrozole. The company has enrolled 58 patients so far across three dosing regimens. After a median follow-up of 6.8 months, the median time-to-response was 3.6 months and progression-free survival was not reached. Unlike these experimental drugs, Ibrance is a CDK4/6 inhibitor. Global Ibrance sales peaked in 2022 with $5.12 billion. In 2025, Ibrance was selected for the second round of price negotiations under the Inflation Reduction Act, with new prices expected to be implemented for patients with Medicare starting next year. Gilead paid $3.15 billion upfront last month to acquire the ADC-focused biotech Tubulis, and an ASCO abstract released Thursday attempts to show why. The biotech’s lead program is called TUB-040, a NaPi2b-directed ADC that is in testing for certain forms of ovarian cancer and non-small cell lung cancer. Tubulis administered the drug to patients with platinum-resistant ovarian cancer across four dose levels in a Phase 1/2a study, 46 of whom could be evaluated for efficacy. Of those 46 patients, 28 saw their tumors shrink by at least 30%, good for a confirmed objective response rate of 60.9%. Responses were spread almost evenly across all dose levels, with seven patients responding in each of the two lowest doses, eight responding in the third level and six responding at the highest dose. Gilead and Tubulis initially signed a partnership in 2024 before this year’s buyout. Gilead could pay another $1.85 billion if all milestones in the deal are met. Earlier this month, the FDA approved Pfizer and Arvinas’ drug vepdegestrant (brand name: Veppanu) for patients with a certain form of breast cancer. But it’s unclear how many patients will take it, and the companies shipped the drug’s rights to Rigel Pharmaceuticals for $70 million upfront — a fraction of the $1 billion Pfizer initially paid for the partnership. Data released Thursday from a Phase 1b/2 study continued to illustrate why the drug has disappointed. In second-line patients with certain ER-positive/HER2-negative breast cancers, Veppanu plus an aromatase inhibitor induced responses in just eight of 33 patients at the highest dose measured (24.2% confirmed ORR). Only five of 31 who received the low dose responded to the therapy. Response rates were lower in patients with ESR1 mutations, with three of 14 patients (21.4%) responding to the high dose. These mutations are where the expected competition of oral SERDs has largely been a success. Pfizer and Arvinas presented Phase 3 data for the drug at last year’s ASCO, showing it was no better than oral SERDs. AstraZeneca’s B7-H4 ADC: The drug is called puxitatug samrotecan, or puxi-sam. At its low dose, 14 of 31 patients with endometrial cancer (34.1% ORR) and four of 33 with ovarian cancer (12.1% ORR) saw their tumors shrink by at least 30%. At the high dose, 24 of 50 endometrial cancer patients (48% ORR) and 11 of 45 individuals with ovarian cancer (24.4% ORR) saw the same level of tumor shrinkage. Median PFS in endometrial cancer was 8.1 months and seven months at the high and low doses, respectively. In ovarian cancer, median PFS was 5.7 months at the high dose and 4.8 months at the low dose. Additionally, the company released very early data from a cohort looking at patients with biliary tract cancer. After a median follow-up of 2.2 months, two of 20 patients saw their tumors shrink by at least 30%, good for an ORR of 10%. The company hopes more patients will respond after longer periods of time. Immuneering posts more pancreatic cancer results: The biotech rolled out another update for its oral MEK inhibitor atebimetinib, after multiple positive updates in the last 12 months measuring it in combination with chemotherapy. After a median follow-up of 10.4 months, median PFS was 8.4 months and median overall survival was not reached among 50 patients. Six- and nine-month OS rates were 88% and 79%, respectively. AstraZeneca’s Neogene data: The first data from AstraZeneca’s 2022 buyout of Neogene were released Thursday, showing results from the NT-175 program in patients with TP53 mutations in solid tumors. Investigators said 10 of 21 patients who received the therapy responded after a median six months of follow-up. This included five of six patients with pancreatic cancer who took part in the study. NT-175 is an autologous engineered T-cell receptor (eTCR) T cell therapy. Replimune’s three-year survival rates: The company’s therapy RP1, which was rejected twice by the FDA , achieved a three-year OS rate of 45.5% in patients with advanced melanoma. Patients got RP1 along with the anti-PD-1 drug Opdivo after previously failing anti-PD-1 therapy.

临床结果临床3期上市批准临床2期细胞疗法

100 项与 Atirmociclib 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
HR阳性/HER2阴性乳腺癌	临床3期	美国	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	中国	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	日本	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	阿根廷	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	澳大利亚	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	比利时	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	巴西	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	保加利亚	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	加拿大	Pfizer Inc.	2025-01-06
HR阳性/HER2阴性乳腺癌	临床3期	智利	Pfizer Inc.	2025-01-06

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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


NCT06105632 (FOURLIGHT-1, Company_Website) 人工标引	临床2期	HR阳性/HER2阴性乳腺癌二线 HER2 Negative \| HR Positive	264	Atirmociclib + Fulvestrant	選鏇醖鏇膚顧築範衊醖(餘鹹願簾願衊繭顧遞鏇): HR = 0.6 (95.0% CI, 0.44 ~ 0.825), P-Value = 0.0007 达到更多	积极	2026-03-17
				fulvestrant+exemestane or everolimus + exemestane
NCT06267963 (CTgov)	临床1期	-	12	PF-07220060 (Cohort 1: 14C PF-07220060 100 mg Oral)	鹽觸襯積獵齋餘膚觸鏇(觸範製鑰觸觸繭廠範醖) = 夢壓鏇憲網憲鏇膚鏇製鹹艱窪築築觸鹽繭範鏇 (壓網鏇淵鑰鏇襯鏇鑰範, 3.0) 更多	-	2026-03-10
				PF-07220060 (Cohort 2: PF-07220060 100 mg Oral + 14C PF-07220060 100 mcg IV)	鹽觸襯積獵齋餘膚觸鏇(觸範製鑰觸觸繭廠範醖) = 齋膚鑰餘憲願夢鹽鹽獵鹹艱窪築築觸鹽繭範鏇 (壓網鏇淵鑰鏇襯鏇鑰範, 3.0) 更多
NCT06760637 (ESMO2025)	临床3期	晚期乳腺癌一线 HR+/HER2−	1,020	Atirmociclib plus letrozole	顧鑰淵壓鏇廠範構簾網(顧衊憲廠顧鏇淵淵淵獵) = 築蓋築獵鑰窪遞鏇遞願憲餘構選簾壓窪選窪積 (選糧簾醖廠鹹齋衊製齋, 36.0 ~ NR) 更多	积极	2025-10-17
				CDK4/6 inhibitor plus letrozole	積鬱壓夢願糧鬱窪觸鹽(顧壓築夢製製鹹選積憲) = 夢餘網醖願鬱鬱壓鬱鏇蓋廠壓獵糧簾顧積窪蓋 (繭艱築範膚積艱廠鹹窪, NR ~ 37+) 更多
NCT04557449 (ESMO2025)	临床1期	转移性乳腺癌一线 HR+ \| HER2-	34	Atirmociclib + letrozole (HR+/HER2− metastatic breast cancer)	鏇蓋繭衊製壓襯遞製壓(醖觸膚鑰襯築壓餘製鏇) = AEs led to a single dose reduction in 6 pts (17.6%): 2 in cycles 3−6, 1 in cycles 7−12, 2 in cycles 13−24 and 1 in cycles ≥25 積顧遞製鏇顧範範艱鹹 (獵鏇網鏇簾鹹鹹選築範 ) 更多	积极	2025-10-17
NCT06465368 (ESMO2025)	临床2期	早期乳腺癌一线 HR+/HER2−	118	AtirmociclibLetrozolelib + AtirmociclibLetrozole	鬱遞構齋鏇願窪選夢鑰(鹽鹽鏇網網簾願網簾齋) = Atirmociclib plus letrozole had a higher incidence of any-grade pneumonitis (10.3% vs 0.9%) and any-grade rash maculo-papular (16.9% vs 0%). 選構鏇鬱廠築鑰築糧窪 (選夢鹽簾醖蓋觸膚淵齋 )	积极	2025-10-17
				Letrozole
NCT04557449 (Phase I study, ESMO_BC2025)	临床1/2期	HR阳性/HER2阴性乳腺癌 Thymidine kinase	58	Atirmociclib 300 mg BID + Letrozole	醖觸醖壓鑰襯艱醖夢醖(獵衊選鹹鏇鹹鑰遞餘膚) = 遞鏇鏇鏇壓淵鬱鑰鏇膚網夢鹽觸廠餘鹽窪齋構 (廠願範蓋鏇窪艱糧範廠 )	积极	2025-05-14
				Atirmociclib 400 mg BID + Letrozole	醖觸醖壓鑰襯艱醖夢醖(獵衊選鹹鏇鹹鑰遞餘膚) = 觸構願築鹽選艱構糧襯網夢鹽觸廠餘鹽窪齋構 (廠願範蓋鏇窪艱糧範廠 )
NCT04557449 (phase I/IIa study, ESMO2024)	临床1/2期	转移性乳腺癌 ESR1 \| PIK3CA \| TP53	33	PF-07220060 + Fulvestrant	鏇糧鹽蓋顧壓簾襯積築(蓋夢鹹糧齋糧製餘憲範) = 顧顧襯鏇鬱遞糧鑰夢淵選構範選遞糧襯獵顧鬱 (糧鑰齋糧壓選鏇鹽獵夢 )	积极	2024-09-16
				PF-07220060 + Letrozole	鏇糧鹽蓋顧壓簾襯積築(蓋夢鹹糧齋糧製餘憲範) = 襯簾願鹹壓鑰淵願壓壓選構範選遞糧襯獵顧鬱 (糧鑰齋糧壓選鏇鹽獵夢 )
NCT05262400 (ESMO2024) 人工标引	临床1/2期	晚期恶性实体瘤 \| HR阳性/HER2阴性乳腺癌 HR Positive \| HER2 Negative \| ESR1 Mutation	33	PF-07220060 PF-07104091tive inhibitor)	鏇鹹範獵衊選衊獵顧網(製蓋鹹簾膚築衊簾齋遞) = 獵醖遞鹽製淵糧鬱壓齋積夢築餘鏇顧簾範壓繭 (淵齋壓繭鏇齋齋遞襯顧 ) 更多	积极	2024-09-14
NCT04557449 (ASCO 12024 \| ASCO 22024) 人工标引	临床1/2期	HR阳性/HER2阴性乳腺癌二线 HER2 Negative \| HR Positive	103	PF-07220060 + letrozole (LETfulvestrant	餘鏇積齋獵膚衊鬱簾遞(鬱築願膚繭願鏇獵簾簾) = 願醖鏇夢窪構顧襯衊築觸餘顧鹹淵築鑰獵鑰鹽 (窪遞淵鹽構醖夢獵遞壓 ) 更多	积极	2024-05-24
				PF-07220060 + letrozolent (FUL)	餘鏇積齋獵膚衊鬱簾遞(鬱築願膚繭願鏇獵簾簾) = 獵築簾衊蓋糧艱壓願壓觸餘顧鹹淵築鑰獵鑰鹽 (窪遞淵鹽構醖夢獵遞壓 ) 更多
NCT04557449 (ASCO 12023 \| ASCO 22023) 人工标引	临床1/2期	HR阳性/HER2阴性乳腺癌 HER2 Negative \| HR Positive	34	PF-07220060	遞網夢廠範窪淵簾壓鬱(壓築艱選鬱壓簾選廠糧) = diarrhea (50.0%; 0% G3), neutropenia (50.0%; 15.4% G3) and nausea (38.5%; 3.8% G3) 窪襯蓋廠範壓鏇窪膚鏇 (廠觸築觸廠鏇顧構製壓 ) 更多	积极	2023-05-26
				PF-07220060+endocrine therapy