A PHASE 1 OPEN-LABEL STUDY OF PF-07985045 AS A SINGLE-AGENT AND IN COMBINATION WITH OTHER ANTI-CANCER AGENTS IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

The purpose of this study is to learn about the safety and effects of the study medicine when given alone or together with other anti-cancer therapies. Anti-cancer therapy is a type of treatment to stop the growth of cancer.
This study also aims to find the best amount of study medication.
This study is seeking participants who have solid tumors (a mass of abnormal cells that forms a lump or growth in the body) that:
* are advanced (cancer that doesn't disappear or stay away with treatment) and
* have a KRAS gene mutation (a change in the DNA of the KRAS gene that can cause cells to grow in very high numbers).
This includes (but limited to) the following cancer types:
* Non-Small Cell Lung Cancer (NSCLC): It's a type of lung cancer where the cells grow slowly but often spread to other parts of the body.
* Colorectal Cancer (CRC): This is a disease where cells in the colon (a part of large intestine) or rectum grow out of control.
* Pancreatic ductal adenocarcinoma (PDAC): This is a cancer that starts in the ducts of the pancreas but can spread quickly to other parts of the body. Pancreas is a long, flat gland that lies in the abdomen behind the stomach. Pancreas creates enzymes that help with digestion. It also makes hormones that can help control your blood sugar levels.
All participants in this study will take the study medication (PF-07985045) as pill by mouth. This will be repeated for 21-day or 28-day cycles.
Depending on which part of the study participants are enrolled into they will receive the study medication (PF-07985045 alone or in combination with other anti-cancer medications). These anti-cancer medications will be given in the study clinic by intravenous (IV) that is directly injected into the veins at different times (depending on the treatment) during the 21-day or 28-day cycle.
Participants can continue to take the study medication (PF-07985045) and the combination anti-cancer therapy until their cancer is no longer responding.
The study will look at the experiences of people receiving the study medicines. This will help see if the study medicines are safe and effective.
Participants will be in this study for up to 4 years. During this time, the participants will come into the clinic for 1 to 4 times in each 21-day or 28-day cycle. After the participants have stopped taking the study medication (at about at 2 years) they will be followed for another two years to see how they are doing

开始日期2024-12-10

申办/合作机构

Pfizer Inc.

NCT04800822

/ Terminated临床1期

A PHASE 1, OPEN-LABEL, MULTI-CENTER, DOSE ESCALATION AND DOSE EXPANSION STUDY TO EVALUATE THE SAFETY, TOLERABILITY, PHARMACOKINETICS, AND PRELIMINARY EVIDENCE OF ANTI-TUMOR ACTIVITY OF PF-07284892 (ARRY-558) AS A SINGLE AGENT AND IN COMBINATION THERAPY IN PARTICIPANTS WITH ADVANCED SOLID TUMORS

The purpose of this first-in-patient, open label study is to determine the maximum tolerated dose and/or recommended dose for further study of PF-07284892 as a single agent and in combination with lorlatinib, encorafenib and cetuximab, or binimetinib and evaluate the pharmacokinetics, safety, and preliminary clinical activity of single agent and each combination therapy.

开始日期2021-03-17

申办/合作机构

Pfizer Inc.

100 项与 PF-07284892 相关的临床结果

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100 项与 PF-07284892 相关的转化医学

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100 项与 PF-07284892 相关的专利（医药）

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项与 PF-07284892 相关的文献（医药）

2023-08-04·Cancer discovery

Patient-Centric Approaches for Phase I Combination Trials Come on Stage

Communications

作者: Hernando-Calvo, Alberto ; Garralda, Elena

Summary::

A disruptive clinical trial design allowed Drilon and colleagues to demonstrate proof of concept of the potential of PF-07284892 to overcome resistance mechanisms to targeted therapies in the clinic.See related article by Drilon et al., p. 1789 (7).

项与 PF-07284892 相关的新闻（医药）

2024-10-21

·精准药物

第5家MNC：辉瑞终止SHP2抑制剂开发

辉瑞公司（Pfizer）已经终止了其SHP2抑制剂PF-07284892的1期研究，这是在癌症治疗领域对SHP2这一靶点的最新打击，此前已有多家制药公司在该靶点上遭遇挫折。根据试验注册更新，辉瑞结束这项研究是“由于战略原因，而不是主要的安全问题、无效性或任何监管机构的请求”。辉瑞在2019年以114亿美元收购Array BioPharma的过程中收购了该药。 SHP2，全称为含Src同源2结构域蛋白酪氨酸磷酸酶，是一个关键的信号节点和调节因子，通过RAS通路促进癌细胞存活和生长，并在癌细胞对靶向治疗产生耐药性的方式中发挥关键作用。 SHP2相关的信号通路（图源：网络） PF-07284892是一种SHP2抑制剂，旨在克服旁路信号介导的耐药性，并在不同的肿瘤模型中证实了这种情况下的活性。 PF-07284892化学结构式（图源：MCE） PF-07284892在2023年美国临床肿瘤学会（ASCO）年会上曾有相关的研究展示，包括作为单药治疗以及与其他靶向疗法联合治疗在耐药性实体瘤中的研究。PF-07284892和劳拉替尼或binimetinib，或西妥昔单抗联用时共5例患者达到部分缓解（PR）。尽管辉瑞决定停止PF-07284892的研究，但其他公司在SHP2抑制剂领域的积极结果为这一靶点带来了新的希望。例如，加科思的JAB-3312与戈来雷塞（KRAS G12C抑制剂）的组合在I/IIa期临床研究中显示出积极的结果，此前15人小样本的客观缓解率高达86.7%，这一数据较现有的标准疗法相比有显著优势。为众多SHP2抑制剂的开发提供了新的视角。在研SHP2抑制剂（图源：凯莱英药闻）小结： 2022年以来，赛诺菲，艾伯维，罗氏，BMS，加上今天的辉瑞，明星靶点SHP2抑制剂相继因各种“战略，商业”原因被MNC退货。目前全球最快的当属加科思的SHP2抑制剂JAB-3068，其正处于三期开发阶段。 First-in-class难，难于上青天！参考资料：辉瑞声明：发表/转载本文仅仅是出于传播信息的需要，并不意味着代表本公众号观点或证实其内容的真实性。据此内容作出的任何判断，后果自负。若有侵权，告知必删！长按关注本公众号粉丝群/投稿/授权/广告等请联系公众号助手觉得本文好看，请点这里↓

ASCO会议临床3期临床结果并购临床2期

2024-10-18

·Endpoints

Pfizer ends trial of Array-acquired SHP2 inhibitor after similar cuts from peers

Pfizer has ended its trial of an SHP2 inhibitor that was being developed in cancer, the latest blow to the target after several other drugmakers have suffered setbacks. The New York drugmaker ended the Phase 1 study of the drug, PF-07284892, “due to strategic reasons, not major safety concerns, futility, or requests from any regulatory authorities,” according to the trial registry update. The experimental medicine is still listed in Pfizer’s pipeline on its website. A spokesperson for the company didn’t provide comment as of publication time. Pfizer acquired the drug as part of its 2019 buyout of Array BioPharma. The $11.4 billion deal came with a portfolio of approved and in-development cancer treatments. It’s not the first company to walk away from SHP2. Earlier this year, Roche ended a pact with Relay Therapeutics, and Bristol Myers Squibb also left a collaboration. AbbVie and Sanofi have ended SHP2 partnership deals as well. Pfizer once hoped for better for its drug, however. In February, Chief Oncology Officer Chris Boshoff described the drug as “differentiated” and “best-in-class.” “The two or three that’s in the clinic has been challenging in terms of side effects, and we don’t see that,” Boshoff said during the company’s oncology innovation day, according to a transcript from AlphaSense. Pfizer was testing PF-07284892 alone and in combination with other drugs, including two of the products that came from the Array deal. The move is one of several cutbacks to Array’s work, including the shutdown of a site in Colorado earlier this year. It’s been a volatile month for Pfizer, which is facing an activist investor and last week stopped developing an investigational RSV treatment, then secured an FDA approval for a hemophilia treatment .

并购上市批准临床1期引进/卖出

2024-02-21

·同写意

加科思SHP2获得三期注册性临床试验批准，产品上市迈出关键一步

加科思药业（1167.HK）近日公布，其自主研发的SHP2抑制剂JAB-3312与KRAS G12C戈来雷塞抑制剂联用在中国获批开展三期临床试验。这一事件标志着SHP2这个还未成药的靶点正式进入三期临床试验，距离获批上市迈出关键一步。此次获批的临床试验为随机对照，实验组为SHP2和KRAS G12C两个口服药联用，而对照组为当前的一线非小细胞肺癌的“金标准”——PD-1和化疗联用，这意味着两个口服药有望取代静脉注射成为KRAS G12C突变的非小细胞肺癌患者的一线疗法。进入三期试验，也说明药监部门认可了这一疗法此前积累的临床数据。加科思的SHP2抑制剂从2018年起在中国和美国开展单药临床试验，彼时走在加科思之前的是老牌药企诺华。随后越来越多公司开始布局SHP2，罗氏、赛诺菲、BMS、辉瑞等MNC相继通过License in的模式展开临床试验，而国内多家公司也陆续布局了这一靶点。和其他未成药的靶点类似，SHP2的研发同样经历了一番波折，从大厂争相高价License in，到遭遇种种困难。加科思曾在2020年以10亿美元的BD交易将自研SHP2产品转让给艾伯维，并获得了1.1亿美元的首付款和里程碑付款。随后的几年，诺华、加科思和辉瑞的研究为SHP2的后续研究探明方向。辉瑞在2023年ASCO上公布的一期临床研究结果显示：PF-07284892能联合靶向ALK、BRAF、ROS1等不同驱动基因的多种药物，有效缩小难治肿瘤。而在2023年ESMO上，加科思的口头报告更是以亮眼的数据找到了SHP2极具潜力的上市路径——与KRAS G12C联用。在戈来雷塞注册试验剂量800毫克（单药注册试验剂量）及2毫克JAB-3312联用的剂量组中，ORR（客观缓解率）为86.7%（13/15），DCR （疾病控制率）100%，和KRAS G12C单药相比，客观缓解率大幅提升。加科思SHP2数据的发布，改变了现有SHP2研发局面，因为其剂量更低（每日仅1-8毫克），安全性更强，潜在的脱靶毒性低，这样的分子更有助于在联合用药中发挥其“增敏剂”作用。相比之下，同类药物的二期临床试验给药剂量都高达20到40毫克之间。美银证券曾发布系列研报盘点全球最具潜力的十大靶点，在SHP2的盘点中，美银称加科思为“全球黑马”，并且用更宏观的视角分析称，SHP2抑制剂的研发目前由美国公司所引领，以加科思为代表的中国公司正成为未来重要的力量。目前虽然有2款已经上市的KRAS G12C抑制剂，但在非小细胞肺癌适应症上单药客观缓解率约为40%，无论是有效性还是安全性都有提升空间，并且所有的KRAS G12C都用于二线治疗，还未成为一线疗法。目前几乎所有研发KRAS G12C抑制剂的企业都在探索进入一线疗法的方案，但方案普遍为KRAS G12C抑制剂与PD-1单抗联用。对于KRAS G12C突变患者而言，目前的一线疗法是PD-1和化疗联合用药，两药联合的客观缓解率在30%-40%左右，并且需要静脉注射。加科思的SHP2抑制剂JAB-3312联合KRAS G12C抑制剂戈来雷塞均为口服制剂，也是目前全球唯一一家双口服制剂在一线治疗NSCLC的临床试验中获批进行三期注册临床试验的药物组合疗法，国际上其它公司启动的针对KRAS G12C突变的非小细胞肺癌（NSCLC）患者的一线治疗为口服的KRAS G12C抑制剂联合静脉注射的化疗或静脉注射的PD-1抗体。两款口服药物的联用将为肿瘤患者带来更便利的给药方式。患者无需住院，在家口服即可，使得生活质量得以进一步提升。凭借超过标准疗法一倍以上的客观缓解率，以及更好的给药方式，JAB-3312与KRAS G12C联用在2024年正式进入三期临床试验，将与标准疗法（化疗和PD-1联用）展开随机对照。此前15人小样本的客观缓解率高达86.7%，这一数据较现有的标准疗法相比有显著优势。若能在三期试验中部分保持其优势，SHP2的获批将成为较大概率事件，且不只是面向中国市场，还能为全球的KRAS G12C突变的非小细胞肺癌患者带来一项全新的治疗选择，使得加科思在SHP2抑制剂的研发和市场化处在全球领先的位置。在后续开发中，SHP2凭借其“增敏剂”特性，有助于在联合用药中发挥作用，除目前正在临床试验阶段的KRAS G12C抑制剂外，还有望与加科思自研的KRASmulti抑制剂JAB-23400进行联合治疗。此外SHP2也有望与针对ALK、ROS1、BRAF V600E等靶点的药物联合用药，从而覆盖更广阔的患者群体。在今年一月，天风证券称加科思为“突破不可成药靶点的小分子创新药黑马”，并预计公司2024年市值为60.92亿港元，目标价7.68港元，较当前市值有翻倍空间。内容来源于网络，如有侵权，请联系删除。

引进/卖出ASCO会议

100 项与 PF-07284892 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
结直肠癌	临床1期	美国	Pfizer Inc.	2024-12-10
结直肠癌	临床1期	日本	Pfizer Inc.	2024-12-10
非小细胞肺癌	临床1期	美国	Pfizer Inc.	2024-12-10
非小细胞肺癌	临床1期	日本	Pfizer Inc.	2024-12-10
胰腺导管腺癌	临床1期	美国	Pfizer Inc.	2024-12-10
胰腺导管腺癌	临床1期	日本	Pfizer Inc.	2024-12-10
晚期恶性实体瘤	临床1期	美国	Pfizer Inc.	2021-03-17
实体瘤	临床申请批准	中国	Pfizer Inc.	2023-02-22

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临床结果

适应症

分期

评价

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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


NCT04800822 (ASCO 12023 \| ASCO 22023) 人工标引	临床1期	实体瘤	33	PF-07284892	鏇廠壓壓製憲鬱築膚願(廠鬱觸窪鹹顧積淵顧觸) = TRAEs; >15%(anemia (21%), peripheral edema (18%), and increased AST (18%).) 鑰獵蓋壓膚鏇觸餘蓋蓋 (願選製範餘淵鹹選獵鏇 )	积极	2023-05-31
				PF-07284892