A Phase II Trial to Evaluate Efficacy and Safety of Erdafitinib in Patients With Advanced Non Small Cell Lung Carcinoma (NSCLC) Harboring Fibroblast Growth Factor Receptor (FGFR) Genetic Alterations After Relapse of Standard Therapy.

In the FIND trial, Non Small Cell Lung Carcinoma (NSCLC) patients with Fibroblast Growth Factor Receptor (FGFR) genetic alteration will be treated with the selective FGFR1-4 inhibitor erdafitinib. Archival samples, fresh frozen tumor samples and blood for circulating tumor DNA (ctDNA) will be collected before treatment. Patients will be treated until disease progression or unacceptable toxicity. In case of progression, fresh frozen tumor biopsies and ctDNA analyses will be performed to assess resistance mechanisms. The primary objective of the trial is to analyze the efficacy of erdafitinib in NSCLC patients with FGFR genetic alterations. NSCLC patient number will be based on a statistical hypothesis aiming at increasing the response rate comparing to chemotherapy/immunotherapy after standard treatment.

开始日期2019-03-25

申办/合作机构-

NCT03788603 / Completed临床1期

An Open Label, Phase 1 Study to Evaluate the Safety, Tolerability and Pharmacokinetics of Rogaratinib (BAY1163877) in Chinese Patients With FGFR-positive Refractory, Locally Advanced, or Metastatic Solid Tumors

This study is planned to determine the safety and tolerability of rogaratinib in Chinese patients with fibroblast growth factor receptor (FGFR)-positive refractory, locally advanced, or metastatic solid tumors and to characterize the pharmacokinetics of rogaratinib in Chinese patients.

开始日期2019-01-07

申办/合作机构

Bayer AG

CTR20180877 / Terminated临床1期

在FGFR阳性难治性局部晚期或转移性实体瘤中国患者中评价试验药物安全性耐受性和PK的开放性I期研究

评价rogaratinib在FGFR阳性、难治性、局部晚期或转移性晚期实体瘤中国患者中的安全性、耐受性及药代动力学特征。

开始日期2019-01-07

申办/合作机构

Bayer AG

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100 项与 FGFR突变肿瘤相关的临床结果

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100 项与 FGFR突变肿瘤相关的转化医学

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0 项与 FGFR突变肿瘤相关的专利（医药）

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项与 FGFR突变肿瘤相关的文献（医药）

2024-05-01·JCO Precision Oncology

Are FGFR Fusions and Mutations the Next Tumor-Agnostic Targets in Oncology?

Article

作者: Ellis, Haley ; Goyal, Lipika

Gong et al present two NCI-MATCH tumor-agnostic trials evaluating erdafitinib for FGFR-altered cancers, marking steppingstones in precision oncology.

2024-02-22·Journal of Medicinal Chemistry1区 · 医学

Identification of Piperazinyl–Difluoro-indene Derivatives Containing Pyridyl Groups as Potent FGFR Inhibitors against FGFR Mutant Tumor: Design, Synthesis, and Biological Evaluation

1区 · 医学

Article

作者: Luo, Lijun ; Chen, Shuting ; Cheng, Shihao ; Shao, Huanjie ; Li, Ying ; Huang, Haihong ; Ding, Wei ; Zhang, Dongfeng ; Yan, Liting ; Sheng, Li

The fibroblast growth factor receptor (FGFR) signaling pathway plays important roles in cellular processes such as proliferation, differentiation, and migration. In this study, we highlighted the potential of FGFR inhibitors bearing the (S)-3,3-difluoro-1-(4-methylpiperazin-1-yl)-2,3-dihydro-1H-indene scaffold containing a crucial 3-pyridyl group for the treatment of FGFR mutant cancers. The representative compound (S)-23, which was identified through comprehensive evaluation, exhibited potent antiproliferative activity with GI₅₀ in the range of 6.4-10.4 nM against FGFR1 fusion protein-carrying, FGFR2-amplified, and FGFR2 mutant cancer cell lines and good antiproliferative activity against FGFR3 translocation and mutant FGFR4 cancer cell lines, as well as potency assessment against FGFR1-4 kinases. Moreover, compound (S)-23 exhibited favorable pharmacokinetic properties, low potential for drug-drug interactions, and very potent antitumor activity in MFE-296 xenograft mouse models with a TGI of 99.1% at the dose of 10 mg/kg. These findings demonstrate that compound (S)-23 is a potential therapeutic agent for FGFR mutant tumors.

2024-01-15·Cancer Research and Treatment

A Phase II Trial of Nintedanib in Patients with Metastatic or Recurrent Head and Neck Squamous Cell Carcinoma: In-Depth Analysis of Nintedanib Arm from the KCSG HN 15-16 TRIUMPH Trial

Article

作者: Lee, Keun-Wook ; Kim, Hye Ryun ; Keam, Bhumsuk ; Kim, Kyoo Hyun ; Ahn, Myung-Ju ; Kim, Jin-Soo ; Ahn, Hee Kyung ; Lim, Sun Min ; Lee, Hyun Woo ; An, Ho Jung ; Lee, Yun-Gyoo

Purpose Precision oncology approach for recurrent and metastatic head and neck squamous cell carcinoma (HNSCC) is necessary due to its dismal prognosis. We performed a genomic profile-based umbrella trial of patients with platinum-refractory HNSCC (KCSG-TRIUMPH). Here, we present an in-depth report of the the nintedanib arm (arm 3) of the current trial.Materials and Methods The TRIUMPH study was a multicenter, open-label, single-arm phase 2 trial, in which patients were assigned to treatment arms based on next-generation sequencing (NGS)–based, matching genomic profiles. Patients whose tumors harbor fibroblast growth factor receptor (FGFR) alteration were enrolled in the nintedanib arm (arm 3) as part of the TRIUMPH study. The primary endpoint was the overall response rate (ORR), and secondary endpoints included overall survival (OS), progression-free survival (PFS), safety, and biomarker analysis.Results Between October 2017 and August 2020, 207 were enrolled in the TRIUMPH study, and eight were enrolled in the nintedanib arm. ORR and disease control rate were 42.9% and 57.1%, respectively. The median PFS was 5.6 months and the median duration of response was 9.1 months. Median OS was 11.1 months. One patient maintained the partial response for 36 months. Overall, the toxicity profiles were manageable.Conclusion Single-agent nintedanib has demonstrated significant efficacy in FGFR-mutated, recurrent or metastatic HNSCC patients, with tolerable toxicity profiles. The results from the study have provided the basis for routine NGS screening and FGFR-targeted therapy. Because of the small number of patients due to slow accrual in this study, further studies with a larger cohort are warranted for statistical power.

项与 FGFR突变肿瘤相关的新闻（医药）

2024-10-01

·BioSpace

GeneCentric Therapeutics Announces Publication of Clinicogenomic Results from GARNER Study in High-Risk Non-Muscle Invasive Bladder Cancer

Study utilized GeneCentric’s RNA-based FGFR Predictive Response Signature (FGFR-PRS) and showed it could identify twice as many patients with an activated FGFR pathway compared to patients with FGFR DNA alteration biomarkers DURHAM, N.C.--(BUSINESS WIRE)-- #GeneCentric -- GeneCentric Therapeutics , a company making precision medicine more precise through RNA-based diagnostics, announced today that results from the GARNER (Genomic Analysis of high-Risk Non-muscle invasive bladder cancER) study were published in Clinical Cancer Research . The GARNER study, the largest high-risk non-muscle invasive bladder cancer (HR-NMIBC) patient cohort ever assembled with both clinical and genomic detail, investigated fibroblast growth factor receptor (FGFR) DNA alteration (ALT) frequency and activation in HR-NMIBC and the clinical outcomes associated with standard-of-care Bacillus Calmette-Guérin (BCG) treatment. The study was conducted by the Erasmus MC Urothelial Cancer Research Group (EUCRG) at the Erasmus MC Cancer Institute. Janssen Research & Development, LLC, a Johnson & Johnson company, and GeneCentric collaborated to perform genomic testing. Although many HR-NMIBC patients respond to BCG treatment, 50-70% have a recurrence, and up to 20% progress to muscle-invasive bladder cancer (MIBC) or locally advanced/metastatic disease. Alternative therapies including FGFR-targeting agents are being investigated. While eligibility for FGFR-targeted therapies has focused on patients who are FGFR ALT (+), DNA alterations may not fully identify all patients who could potentially benefit from FGFR-targeted therapy. In this study, GeneCentric’s novel RNA-based FGFR-PRS identified approximately two-fold more patients with an activated FGFR pathway compared to those who were FGFR ALT (+). “GeneCentric is intensely focused on developing RNA-based signatures, because DNA alterations and other biomarkers may have limitations in identifying all patients who could potentially benefit from targeted therapies,” said Kirk Beebe, PhD, Chief Scientific Officer at GeneCentric. “The GARNER study allowed us to apply the FGFR-PRS to tumors from a high-risk group of patients with bladder cancer to show that the prevalence of FGFR-PRS positive tumors was much higher than the number of tumors identified with FGFR DNA alterations. Beyond HR-NMIBC, we have developed gene signatures for a broad range of targeted therapies, with a vision for this approach eventually becoming the paradigm for patient selection as an adjunct or in place of DNA alteration testing.” Findings related to the FGFR-PRS from the study include: The FGFR alteration frequency (i.e., FGFR ALT (+)) in HR-NMIBC tumors was 31%. The frequency of FGFR-activated tumors using the FGFR-PRS was more than twice as high as FGFR ALT+ at 75%. This enrichment of tumors that may be FGFR-activated identified by the FGFR-PRS compared to FGFR-altered tumors was also observed in more advanced-stage disease (muscle-invasive and metastatic urothelial cancer). About the GARNER Study The GARNER study is the largest HR-NMIBC real-world patient cohort ever assembled with both clinical and genomic detail and the first study of the broader GARNER Bladder Cancer Program. The study is comprised of a cohort of almost 1,200 NMIBC patients who underwent surgery and adjuvant BCG treatment. The study was conducted by Tahlita Zuiverloon, MD, PhD, Principal Investigator at the Department of Urology at Erasmus MC Urothelial Cancer Research Group (EUCRG) at the Erasmus MC Cancer Institute. Janssen Research & Development, LLC, a Johnson & Johnson company, and GeneCentric Therapeutics performed retrospective genomic analysis of longitudinal samples collected in this study. About GeneCentric GeneCentric Therapeutics, Inc., a leader in RNA-based genomic biomarker and next-generation companion diagnostics development, is based in Durham, North Carolina. They have developed a deep pipeline of gene signatures and related diagnostic tests by parsing the complexity of tumor biology using their RNA-based Tumor and Immune Micro-Environment (rT(I)ME) Explorer platform and AI technology to identify responder populations to oncology therapeutics. Using their ExpressCT (Expression Signatures Through Circulating Tumor Signals) platform, these signatures can be applied to liquid biopsy. GeneCentric commercializes its technology through strategic collaborations with biopharmaceutical and diagnostics companies in applications throughout preclinical testing, clinical drug development and diagnostic test commercialization lifecycle phases. For more information, visit or follow us on LinkedIn . Contacts Robin Fastenau Robin.Fastenau@GeneCentric.com

临床研究临床结果基因疗法siRNA

2024-09-07

·药明康德

男性发病率为女性的3-4倍！针对这种恶性疾病的首款靶向疗法是如何诞生的？

▎药明康德内容团队编辑加里·普莱斯（Gary Price）是一名晚期膀胱癌（尿路上皮癌的一种）患者，自2013年患上膀胱癌后，他与这种疾病进行了长久的抗争。2016年，积极的化疗依然没能阻止癌症的进展，医生告知普莱斯需要做好最坏的打算：“你的生命可能只剩下几个月了。” 好在，普莱斯最终等来了转机。在检测了普莱斯的肿瘤样本后，医生发现他的肿瘤细胞中有一种名为成纤维细胞生长因子受体（FGFR）的基因发生了突变，这使他有机会参加一种名为厄达替尼（erdafitinib）的FGFR靶向新药的临床试验。在厄达替尼的作用下，普莱斯成功活过了医生预言的“死期”，并在很长一段时间内与体内的肿瘤和平共处。在这篇文章中，我们将通过普莱斯的故事为大家介绍这款FDA批准的首款针对转移性膀胱癌的靶向疗法——厄达替尼。一种男性发病率为女性的3-4倍的严重疾病膀胱癌的高发年龄为50-70岁，男性的发病率是女性的3-4倍，影响着全世界数百万人。仅在2020年，全球就有超过21万人死于膀胱癌。不过，相比于其他类型的癌症，膀胱癌的初期症状十分明显，因此患者有机会在疾病早期及时发现癌症，并进行治疗。膀胱癌的初期症状包括血尿、尿频、排尿困难或疼痛等排尿变化。2013年夏天，53岁的普莱斯发现自己有了血尿的症状。起初，普莱斯并未放在心上，以为只是自己最近太累了。但随着后来血尿频繁发生，他不得不重视了起来。在医院进行了一系列的检查后，普莱斯得到了一个令他无法接受的结果——他患上了膀胱癌。就在普莱斯认为自己被宣判了死刑时，医生又给了他希望：“你的癌症还没扩散，还有办法治疗。” 普莱斯决定积极接受各种治疗。几天后，医生从普莱斯肚子里切除了一个台球般大小的肿瘤，并给他进行了卡介苗的治疗。然而，这些常规的干预手段没能阻止普莱斯的肿瘤继续生长，在随后的一年里，他的肿瘤长了切，切了又长。无奈之下，普莱斯选择听从医生的建议，进行更大范围的切除手术。图片来源：123RF 那场手术进行了整整15个小时，医生切除了普莱斯的膀胱、已经无法正常工作的右肾、右输尿管和前列腺。尽管失去膀胱令普莱斯挂上了尿袋，只能通过腹部的造口排出尿液，但乐观的普莱斯认为，这场手术令他能够暂时脱离癌症的魔掌，有机会调整身心状态，继续和病魔作斗争。在度过了将近1年的无癌时光后，2016年4月，普莱斯在随访时发现他的癌症复发了。尽管普莱斯随后接受了积极的化疗，但他体内的癌细胞依然没有得到控制，医生只能让他做好最坏的打算。但普莱斯和医生都没有就此放弃，他们决定对肿瘤样本进行检测，看看是否有潜在的靶向治疗可以用。幸运的是，医生发现普莱斯的肿瘤中携带着FGFR3基因突变，该基因编码的蛋白属于FGFR家族，这类受体酪氨酸激酶可能在多种类型的肿瘤细胞中被上调，参与了肿瘤细胞的分化和增殖、肿瘤血管生成，还有肿瘤细胞存活。也就是说，普莱斯很有可能从FGFR靶向治疗中获益。而更幸运的是，普莱斯的肿瘤医生正好参与了一项针对FGFR突变癌症患者的新药研究，旨在评估一种名为厄达替尼的新型泛FGFR抑制剂，而普莱斯的情况也恰好满足临床试验的入组标准。普莱斯当即决定加入这项临床试验，回想起当时，他说：“我觉得这是我做的最好的决定。” 一种泛FGFR抑制剂厄达替尼（曾用名为JNJ-42756493）是强生（Johnson & Johnson）与Astex Pharmaceuticals公司合作发现的新型、高效、具选择性的FGFR1-4小分子抑制剂。该药物会被细胞内的溶酶体摄取，从而能够长期抑制FGFR通路的信号转导。在临床前研究中，厄达替尼对携带FGFR激活变异的人类肿瘤细胞异种移植模型以及来自癌症患者的肿瘤组织均展现出抗肿瘤活性。这些积极的早期研究成果为后续厄达替尼的临床转化提供了强有力的依据。 ▲Erdafitinib的分子结构式（图片来源：PubChem）研究表明，FGFR基因变异（包括突变和基因融合）在多种肿瘤的进展中发挥了关键作用，如肝癌、肺癌、胃癌、乳腺癌和尿路上皮癌。研究人员推测，厄达替尼对携带FGFR基因变异的肿瘤都会有一定的抗癌作用。因此，厄达替尼的首个探索性1期研究针对的是晚期实体肿瘤患者，这些患者携带或不携带FGFR基因变异，并且已经没有可用的标准抗肿瘤治疗。在这项研究中，接受厄达替尼治疗的23名携带FGFR基因变异的患者中有16名保持疾病稳定（SD）状态，有4名获得了部分缓解（PR），而36名没有FGFR基因变异的患者均没能从厄达替尼的治疗中获益。也就是说，厄达替尼确实能够对携带FGFR基因变异的晚期实体瘤患者起效。不仅如此，厄达替尼对尿路上皮癌的治疗效果似乎格外出色，3名经确认部分缓解的患者均为尿路上皮癌患者。基于这项研究的结果，研究人员专门针对晚期/转移性尿路上皮癌患者开展了一项2期临床试验，普莱斯参与的正是这项临床试验。让患者与癌症“和谐共处” 这项2期临床试验招募的都是像普莱斯这样携带指定的FGFR基因变异的尿路上皮癌患者，他们的癌症已是晚期，不适合再进行手术。所有这些患者已对化疗耐药，约有四分之一的患者还曾接受过免疫检查点抑制剂治疗，但也未能从中获益。对于这些患者来说，这款靶向疗法就像在黑夜中燃起的一道火光，或许能给身处绝境的他们带来一丝转机。加入临床试验后，普莱斯开始按照医生的指示服用厄达替尼。这款疗法虽然没有非常神奇地令普莱斯的肿瘤完全消失不见，但也持久地控制住了肿瘤的生长——在持续服药的数年时间里，他的肿瘤一直保持着豌豆大小。在这期间，普莱斯学会了如何与癌症“和谐共处”。尽管厄达替尼给他带来了一些恼人的副作用，例如手脚疼痛、指甲脱落、尝不出咸味等等，但这款药物也给他带来了一段新的生命。他不用再把时间浪费在住院治疗上，还能有机会像普通人一样过好自己的生活。他依然每天去上班，闲暇时间也会和妻子一起参加飞碟射击比赛。对于普莱斯来说，现在的每一天都是“赚来的”，也是对他来说有可能获得的最好的生活状态了。为晚期尿路上皮癌患者送去福音 2019年，也就是普莱斯服药的第三年，基于普莱斯参加的这项2期临床试验的积极结果，厄达替尼获得了美国FDA的加速批准，成为了FDA批准的首款口服FGFR激酶抑制剂，也是首款针对转移性膀胱癌的靶向疗法。该疗法获批的适应症为接受铂类化疗后疾病仍然进展的局部晚期或转移性膀胱癌成人患者，这些肿瘤需携带特定的FGFR3或FGFR2基因突变。在这些接受过化疗并且疾病继续进展的87名患者中，32.2%的患者在接受厄达替尼的治疗后获得了缓解，其中有2.3%的患者获得了完全缓解。此外，厄达替尼对那些对抗PD-1/PD-L1疗法没有应答的患者也有疗效。好消息接连传来，今年1月，基于临床3期试验THOR的积极结果，厄达替尼获得了美国FDA的完全批准，用于治疗局部晚期或转移性尿路上皮癌成人患者，这些患者需带有FGFR3遗传变异并经过至少一线系统性治疗后疾病发生进展。在这项研究中，厄达替尼用于之前接受过PD-1/PD-L1抑制剂治疗患者的二线治疗时，与化疗相比将患者的中位生存期延长了4个月，并降低了患者36%的死亡风险。系统性铂类化疗是晚期尿路上皮癌患者的标准治疗，但即使接受化疗，其5年生存率也仅有13-15%。免疫检查点抑制剂是此类患者的另一种选择，然而，只有少部分患者能从中获益。这些对传统化疗或免疫检查点抑制剂应答不佳的患者急需新的治疗方法来缓解疾病，延长生命。根据美国癌症学会（ACS）的统计，2024年美国将有超过8.3万例新发膀胱癌病例，约有四分之一的患者在发现时已是晚期。研究表明，大约有20%的转移性尿路上皮癌患者携带FGFR基因变异，口服形式厄达替尼的获批对这部分患者有着重要意义，为他们提供了一种全新的、非化疗的、便于使用且有效的治疗选择。图片来源：123RF 不仅如此，有文献报道，2010年美国在膀胱癌上的护理成本高达40亿美元，预计到2020年将上升至50亿美元。其中，疾病复发和治疗并发症的管理是导致高护理成本的重要原因。而通过提供有效的靶向治疗，厄达替尼有望在某种程度上减轻患者和社会的经济负担，减少由于病情恶化和多次治疗带来的额外医疗费用。释放无限潜力作为一款靶向在多种肿瘤的进展中具有关键作用的FGFR激酶的抑制剂，厄达替尼具有成为“不限癌种”疗法的潜力。除了局部晚期或转移性尿路上皮癌，研究人员还在前列腺癌、晚期肝细胞癌、晚期难治性实体瘤、儿童非霍奇金淋巴瘤、多发性骨髓瘤、晚期非小肺癌、食管癌或胆管癌患者中开展了厄达替尼的2期临床试验。 2022年6月，强生公布了厄达替尼治疗具有特定FGFR突变的晚期实体瘤患者的2期临床试验数据。在该研究中，厄达替尼对14种不同类型的癌症均有效果，其中还包含唾液腺癌、胰腺癌、胶质母细胞瘤这类难以治疗的癌症。总体而言，在178名不同癌种患者中有29.2%获得了缓解，43.3%患者的肿瘤保持稳定。也就是说，无论患者的肿瘤位置与组织学种类如何，通过靶向抑制FGFR受体，厄达替尼有潜力为广大FGFR驱动肿瘤的晚期患者提供一种新的、专一性更强的治疗，尤其是那些肿瘤类型罕见或现有治疗手段匮乏的患者。除了在适应症上不断突破边界，厄达替尼还在挖掘更多的潜能，例如与免疫检查点抑制剂的联合使用，以及与新型膀胱内药物输送系统相结合。在与强生的在研PD-1抑制剂cetrelimab联用治疗不适合以顺铂为基础化疗的转移性尿路上皮癌初治患者的2期临床试验中，厄达替尼单药治疗组的客观缓解率（ORR）为44.2%，仅1例患者获得了完全缓解，而与cetrelimab联用组患者的ORR为54.5%，6例患者获得了完全缓解，患者的无进展生存期也更长（10.97个月对比5.62个月）。 TAR-210是一种新型膀胱内药物输送系统，通过一个长硅胶管，可在较长时间内以非常低的剂量持续局部释放厄达替尼。在一项1期临床试验中，TAR-210用于治疗带有特定FGFR基因变异的复发性、中危非肌层浸润性膀胱癌患者，31例患者的完全缓解率高达90%！期待厄达替尼后续能为我们带来更多好消息，也期待更多类似于厄达替尼的突破性药物被研发出来，为癌症患者提供更加安全有效的治疗选择，帮助他们在抗击疾病的道路上迎来更美好的未来！ ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放参考资料（可上下滑动查看） [1] Gary Price: Living the Best Life Possible with Metastatic Bladder Cancer. Retrieved July 24, 2024, from https://cancerprogressreport-aacr-org.libproxy1.nus.edu.sg/report/survivor-journeys/cpr19-survivors-price/ [2] Astex Pharmaceuticals官网. From https://astx.com/research-development/partnered-products-and-programs/balversa-erdafitinib-fgfr-inhibitor-oncology/ [3] Benjamin DJ, Hsu R. Treatment approaches for FGFR-altered urothelial carcinoma: targeted therapies and immunotherapy. Front Immunol. 2023 Aug 22;14:1258388. doi: 10.3389/fimmu.2023.1258388. PMID: 37675102; PMCID: PMC10477976. [4] D'Angelo A, Bagby S, Galli IC, Bortoletti C, Roviello G. Overview of the clinical use of erdafitinib as a treatment option for the metastatic urothelial carcinoma: where do we stand. Expert Rev Clin Pharmacol. 2020 Oct;13(10):1139-1146. doi: 10.1080/17512433.2020.1823830. Epub 2020 Oct 6. PMID: 32935605. [5] Montazeri K, Bellmunt J. Erdafitinib for the treatment of metastatic bladder cancer. Expert Rev Clin Pharmacol. 2020 Jan;13(1):1-6. doi: 10.1080/17512433.2020.1702025. Epub 2019 Dec 22. PMID: 31810398. [6] Astex announces new drug discovery collaboration with University of Newcastle upon Tyne and CRT. Retrieved August 5, 2024, from https://www.cancerresearchhorizons.com/news/astex-announces-new-drug-discovery-collaboration-university-newcastle-upon-tyne-and-crt [7] Perera TPS, Jovcheva E, Mevellec L, Vialard J, De Lange D, Verhulst T, Paulussen C, Van De Ven K, King P, Freyne E, Rees DC, Squires M, Saxty G, Page M, Murray CW, Gilissen R, Ward G, Thompson NT, Newell DR, Cheng N, Xie L, Yang J, Platero SJ, Karkera JD, Moy C, Angibaud P, Laquerre S, Lorenzi MV. Discovery and Pharmacological Characterization of JNJ-42756493 (Erdafitinib), a Functionally Selective Small-Molecule FGFR Family Inhibitor. Mol Cancer Ther. 2017 Jun;16(6):1010-1020. doi: 10.1158/1535-7163.MCT-16-0589. Epub 2017 Mar 24. PMID: 28341788. [8] Tabernero J, Bahleda R, Dienstmann R, Infante JR, Mita A, Italiano A, Calvo E, Moreno V, Adamo B, Gazzah A, Zhong B, Platero SJ, Smit JW, Stuyckens K, Chatterjee-Kishore M, Rodon J, Peddareddigari V, Luo FR, Soria JC. Phase I Dose-Escalation Study of JNJ-42756493, an Oral Pan-Fibroblast Growth Factor Receptor Inhibitor, in Patients With Advanced Solid Tumors. J Clin Oncol. 2015 Oct 20;33(30):3401-8. doi: 10.1200/JCO.2014.60.7341. Epub 2015 Aug 31. PMID: 26324363. [9] Botteman, M.F., Pashos, C.L., Redaelli, A. et al. The health economics of bladder cancer. Pharmacoeconomic 21, 1315–1330 (2003). https://doi-org.libproxy1.nus.edu.sg/10.1007/BF03262330 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。版权说明：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。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。分享，点赞，在看，聚焦全球生物医药健康创新

临床研究

2024-04-12

·医药观澜

入选 “突破性研究”，药捷安康公布FGFR抑制剂研究结果

▎药明康德内容团队报道4月12日，药捷安康宣布在2024年美国癌症研究协会（AACR）上公开核心产品tinengotinib针对携带FGFR1-3变异晚期泛实体瘤（单药）的最新研究成果。该项临床结果还入选了本次AACR会议的Late-Breaking Research（突破性研究）环节。成纤维细胞生长因子受体（FGFR）的变异广泛出现于多种恶性肿瘤中，是常见的致癌驱动因子。FGFR抑制剂已被证实对部分携带FGFR变异的肿瘤有效。然而，全球范围内尚无能够治疗携带FGFR1-3突变的晚期泛实体瘤的产品获批上市。Tinengotinib是药捷安康研发的一款创新激酶谱选择性小分子激酶抑制剂，通过靶向肿瘤细胞和改善肿瘤微环境发挥抗肿瘤作用。该产品已经在中国、美国、韩国、欧洲等地开展针对胆管癌的全球多中心注册性3期临床试验。根据药捷安康新闻稿介绍，tinengotinib和FGFR有非常特异性的结合模式，使得该产品对一系列FGFR 1-3的突变都保留了高活性。这些突变包括守门员突变、分子刹车突变、不可逆抑制剂结合位点突变等，这是该产品的差异化特点，也显示了tinengotinib针对FGFR变异的泛癌种治疗潜力。在大会上，药捷安康展示了tinengotinib针对携带FGFR1-3突变的晚期泛实体瘤患者的汇总研究数据。回顾性分析数据显示，tinengotinib针对多种癌症都有疗效信号，包括胆管癌、乳腺癌、前列腺癌、尿路上皮癌、结肠癌及头颈癌。最佳客观缓解率（BoR）为33.3%，疾病控制率（DCR）为88.2%，中位无进展生存期（mPFS）6.90个月。药捷安康新闻稿表示，该积极的临床结果验证了tinengotinib针对FGFR突变肿瘤的治疗潜力。参考资料：[1]【2024 AACR Late Breaking】药捷安康公布tinengotinib针对FGFR1-3变异的泛实体瘤临床数据. Retrieved Apr 12, 2024, from https://mp.weixin.qq.com/s/uqYS2KeIjhBAQZU_Y6sL2Q本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权请在「医药观澜」微信公众号留言联系我们。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。

AACR会议临床结果突破性疗法上市批准临床3期