更新于：2024-11-01

FGFR2

更新于：2024-11-01

基本信息

别名

2型成纤维细胞生长因子受体、bacteria-expressed kinase、BEK

+ [18]

简介

Tyrosine-protein kinase that acts as cell-surface receptor for fibroblast growth factors and plays an essential role in the regulation of cell proliferation, differentiation, migration and apoptosis, and in the regulation of embryonic development. Required for normal embryonic patterning, trophoblast function, limb bud development, lung morphogenesis, osteogenesis and skin development. Plays an essential role in the regulation of osteoblast differentiation, proliferation and apoptosis, and is required for normal skeleton development. Promotes cell proliferation in keratinocytes and immature osteoblasts, but promotes apoptosis in differentiated osteoblasts. Phosphorylates PLCG1, FRS2 and PAK4. Ligand binding leads to the activation of several signaling cascades. Activation of PLCG1 leads to the production of the cellular signaling molecules diacylglycerol and inositol 1,4,5-trisphosphate. Phosphorylation of FRS2 triggers recruitment of GRB2, GAB1, PIK3R1 and SOS1, and mediates activation of RAS, MAPK1/ERK2, MAPK3/ERK1 and the MAP kinase signaling pathway, as well as of the AKT1 signaling pathway. FGFR2 signaling is down-regulated by ubiquitination, internalization and degradation. Mutations that lead to constitutive kinase activation or impair normal FGFR2 maturation, internalization and degradation lead to aberrant signaling. Over-expressed FGFR2 promotes activation of STAT1.

关联

125

项与 FGFR2 相关的药物

Tasurgratinib

靶点

FGFR1 x FGFR2 x FGFR3

作用机制

FGFR1拮抗剂 [+2]

在研机构

Eisai Co., Ltd.

原研机构

Eisai Co., Ltd.

在研适应症

FGFR2融合或重排的胆管癌 [+4]

非在研适应症-

最高研发阶段批准上市

首次获批国家/地区

日本

首次获批日期2024-09-24

Futibatinib

福巴替尼

靶点

FGFR1 x FGFR2 x FGFR3 x FGFR4

作用机制

FGFR1拮抗剂 [+3]

在研机构

Taiho Oncology, Inc. [+2]

原研机构

Taiho Pharmaceutical Co., Ltd.

在研适应症

FGFR2融合或重排的胆管癌 [+15]

非在研适应症

晚期恶性实体瘤 [+5]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2022-09-30

Infigratinib Phosphate

英菲格拉替尼

靶点

FGFR1 x FGFR2 x FGFR3 x FGFR4

作用机制

FGFR1拮抗剂 [+3]

在研机构

Alcami Carolinas Corp. [+8]

原研机构

QED Therapeutics, Inc.初创企业

在研适应症

FGFR2融合或重排的胆管癌 [+11]

非在研适应症

晚期胆道癌 [+22]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2021-05-28

1,395

项与 FGFR2 相关的临床试验

NCT05077215 / Not yet recruiting临床3期

A Phase 3, Randomized, Open-Label, Active-Controlled, Superiority Trial of EG007, Added to the Combination of Lenvatinib Plus Pembrolizumab Vs. Lenvatinib Plus Pembrolizumab in Patients with Advanced Endometrial Cancer

This is a Phase 3, multicenter, randomized, open-label trial to evaluate whether EG-007 plus Len+Pem is superior to Len+Pem alone in patients with advanced endometrial cancer (Stage III or IV). This trial will be preceded by a safety lead-in study with up to 28 patients (the safety lead-in is a separate, free-standing protocol).
Approximately 450 patients will be randomized equally (1:1) to receive EG-007 plus Len+Pem or Len+Pem alone. The randomization will be stratified by the following stratification factors:
* Diagnosis Classification (advanced Stage III/IV vs. recurrent endometrial cancer)
* ECOG score at baseline (0 vs 1)
* Geographic region (Asia vs ROW)

开始日期2025-12-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT05106127 / Not yet recruiting临床2期

A Phase 2, Open-Label, Safety Lead-In with Long Term Safety Study of EG-007, Added to the Combination of Lenvatinib Plus Pembrolizumab

This is a Phase 2 trial Safety Lead-in trial conducted in 3 cohorts of patients.
A safety lead-in study of the impact of adding the Repurposed Drugs a third agent will be conducted prior to opening enrollment into the compassionate use study. All patients enrolled in the safety lead-in study may continue long-term treatment under this protocol without interruption of dosing.

开始日期2025-08-01

申办/合作机构

Evergreen Therapeutics, Inc

NCT06454409 / Not yet recruiting临床1期IIT

A Phase 1b Study of the Multi-Kinase Inhibitor Regorafenib in Combination With the BCL-2 Inhibitor Venetoclax Plus Azacitidine in Patients With Relapsed/Refractory Acute Myeloid Leukemia

This phase Ib trial tests the safety, side effects, best dose and effectiveness of regorafenib in combination with venetoclax and azacitidine in treating patients with acute myeloid leukemia (AML) that has come back after a period of improvement (relapsed) or that has not responded to previous treatment (refractory). Regorafenib is in a class of medications called kinase inhibitors. It works by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps to slow or stop the spread of cancer cells. Venetoclax is in a class of medications called B-cell lymphoma-2 (BCL-2) inhibitors. It may stop the growth of cancer cells by blocking BCL-2, a protein needed for cancer cell survival. Azacitidine is in a class of medications called demethylation agents. It works by helping the bone marrow to produce normal blood cells and by killing abnormal cells. Giving regorafenib in combination with venetoclax and azacitidine may be safe, tolerable and/or effective in treating patients with relapsed or refractory AML.

开始日期2025-03-20

申办/合作机构

City of Hope National Medical Center

[+1]

100 项与 FGFR2 相关的临床结果

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100 项与 FGFR2 相关的转化医学

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0 项与 FGFR2 相关的专利（医药）

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4,033

项与 FGFR2 相关的文献（医药）

2024-12-31·Journal of the International Society of Sports Nutrition

The impact of tangeretin combined with whey protein on exercise-induced bronchoconstriction in professional athletes: a placebo-controlled trial

Article

作者: Zhao, Can ; Gao, Bing-Hong ; Mo, Shiwei ; Cao, Zhi ; Liu, Meng

BACKGROUNDExercise-induced bronchoconstriction (EIB) is highly prevalent in athletes. The objective of this study was to assess the therapeutic efficacy of daily tangeretin combined with whey protein supplementation over a period of 4 weeks in professional athletes with EIB.METHODSUsing a placebo-controlled, double-blind, paired, randomized trial design, a cohort of 30 professional athletes with EIB, consisting of 14 females and 16 males, was divided into two groups: the tangeretin combined with whey protein intervention group (TIG), and the placebo control group (PCG). Both the TIG and PCG underwent exercise challenge tests (ECT) and VO_2max tests before (ECT₁, V1) and after (ECT₂, V2) the intervention. Blood (eosinophils, neutrophils, and basophils) and serum (interleukin-5, IL-5; interleukin-8, IL-8; Clara cell secretory protein-16, CC16; immunoglobulin E, IgE) levels were measured early in the morning of ECT₁ and ECT₂, respectively. Lung function was assessed immediately before and post-ECT immediately.RESULTSTangeretin combined with whey protein use for 4 weeks attenuated the decrease in forced expiratory volume in 1 s (FEV₁) post trials (∆FEV₁(ECT1-ECT2): mean (SD) TIG -7.51(6.9)% vs. PCG -2.33(11.49)%, p = 0.013). Tangeretin also substantially attenuated IL-5 concentration (∆IL-5(T₁-T₅): Tangeretin -19.4% vs Placebo + 8.37%, p = 0.022); IL-8 concentration (∆IL-8(T₁-T₅): Tangeretin -17.28% vs Placebo + 6.1%, p = 0.012); CC16 concentration (∆CC16(T₁-T₅): Tangeretin -11.77% vs Placebo + 24.19%); and IgE concentration in the serum (∆IgE(T₁-T₅): Tangeretin -24.1% vs Placebo -3.9%), and significantly decreased neutrophil count (∆N(T₁-T₅): Tangeretin -11.34% vs Placebo + 0.3%) and eosinophil count in blood (∆N(T₁-T₅): Tangeretin -38.5% vs Placebo + 4.35%). Compared with V1, VO_2max (p = 0.042) and TLim (p = 0.05) of V2 were significantly increased in the TIG, and there was no significant change in the PCG. Meanwhile, six athletes in the TIG and 0 athletes in the PCG became EIB-negative at ECT₂; the overall negative conversion rate of EIB was 40.00% in TCG. Additionally, the number of cough symptoms decreased from 9 to 3 and dyspnea from 4 to 2 in the TIG.CONCLUSIONAfter high-intensity exercise, athletes with EIB achieved significant improvements in lung function and blood inflammatory factors by combining tangeretin and whey protein supplementation. EIB athletes also showed longer exercise endurance and VO_2max at 4 weeks after TI. In addition, some patient symptoms disappeared after combination supplementation. The effect of this treatment on professional athletes with EIB was beneficial.

2024-12-01·Science of The Total Environment

Organotin exposure and DNA methylation in non-syndromic cleft lip and palate: Integrating findings from case-control studies and animal experiments

Article

作者: Jin, Lei ; Wang, Linlin ; Chen, Yongyan ; Ren, Aiguo ; Li, Sainan ; Li, Zhiwen ; Cheng, Qianhui

Human exposure to organotin is common but little is known about the adverse pregnancy outcomes. This study aimed to explore the association between organotin exposure and the risk of non-syndromic cleft lip with or without cleft palate (NSCL/P) and to explore the underlying mechanism. Placental samples (109 NSCL/P cases and 128 controls) were analyzed for 8 organotin concentrations, and subsequent animal experiments were conducted by administering tributyltin (TBT) during critical developmental periods. DNA methylation BeadChip analysis (12 NSCL/P and 12 controls), bisulfite Sequencing analysis (3 NSCL/P and 3 controls mice), and RNA sequencing were performed to explore epigenetic mechanisms. Logistic regression, LASSO regression, support vector machine, random forest, and mediation effect analysis were utilized to identify key genes related to TBT and NSCL/P. Only tributyltin met the detection criteria for further analysis among 8 compounds. The median levels of TBT in cases (8.93 ng/g) were statistically significantly higher than those in controls (5.33 ng/g). Excessive TBT exposure in maternal placenta was associated with an increased risk of NSCL/P (OR = 6.44, 95 % CI, 2.91-14.25) in humans, showing a dose-response relationship (p for trend <0.05). 288 differentially methylated CpG sites in 129 genes were identified between cases and controls. Tributyltin was associated with FGFR2 and SCD hypomethylation, which were identified as potential key genes associated with NSCL/P. Mediation analysis suggested that DNA methylation of FGFR2 and SCD may mediate the impact of TBT on NSCL/P occurrence. TBT exposure during the critical period in mice (GD8.5-GD15.5) can induce progeny NSCL/P. Altered FGFR2 and SCD hypomethylation and gene expression observed in response to TBT exposure in fetal mice. Excessive TBT exposure was associated with increased risks of human NSCL/P. TBT exposure can induce NSCL/P in fetal mice. FGFR2 and SCD were implicated in NSCL/P pathogenesis, potentially mediated by DNA methylation alterations.

2024-12-01·Molecular Biology Reports

Investigating FGFR2 gene as a blood-based epigenetic biomarker in gastric cancer

Article

作者: Abolhasani, Naeimeh ; Moradi, Arash ; Abdollahi, Mahvash ; Aleyasin, Seyed Ahmad

BACKGROUNDGastric adenocarcinoma is a prevalent form of cancer that often remains undetected in its early stages due to the lack of specific symptoms. This delayed diagnosis leads to poor clinical outcomes, underscoring the need for an effective and non-invasive method for early detection. Recent advances in cancer epigenetics have led to the identification of biomarkers that have the potential to revolutionize the early detection and monitoring of this disease. One such promising biomarker is the methylation of the FGFR2 promoter. This study aims to measure the methylation levels of a specific CpG site in the FGFR2 promoter gene in DNA extracted from blood leukocytes from patients with intestinal metaplasia, gastric cancer, and healthy control.MATERIAL AND METHODSThe CpG site of the FGFR2 gene promoter was identified in its control region. Methylation alteration of the selected FGFR2 CpG site was determined through the (methylation-sensitive restriction enzyme) MSRE-qPCR. Genomic DNA was extracted from one hundred twenty-five participants.RESULTSThe normal group had mean methylation levels of 93.23 ± 4.929%, while the IM group had a level of 69.85 ± 27.15%. In GC patients, the levels varied, with 25.96 ± 18.98% in the intestinal type and 28.30 ± 16.07% in the diffuse type. The methylation levels in the IM and GC patients were significantly lower than those in the normal control group. However, no significant difference was observed between the methylation status of the intestinal type of GC and the diffuse type. The Receiver operating characteristic (ROC) curve analysis showed that FGFR2 CpG methylation levels in GC patients compared to normal controls had a high sensitivity of 100% and specificity of 100%, with a cut-off of < 74.25%; when GC patients were compared to IM patients, the sensitivity was 85%, and the specificity was 80%, with a cut-off < 44.45%.CONCLUSIONSThe potential of the FGFR2 methylation status as a non-invasive biomarker lies in its ability to be detected in blood leukocytes, which makes it a promising tool for the early detection of intestinal metaplasia and gastric cancer. This could significantly improve the detection and management of these gastric conditions.

471

项与 FGFR2 相关的新闻（医药）

2024-10-28

·药明康德

100%疾病控制率！潜在“first-in-class”小分子抑制剂完成临床概念验证

▎药明康德内容团队编辑日前，Tyra Biosciences公布其在研潜在“first-in-class”FGFR3靶向抑制剂TYRA-300在SURF301临床1/2期研究中治疗转移性尿路上皮癌（mUC）患者的临床概念验证数据。分析显示，接受每日一次≥90 mg TYRA-300、带有FGFR3突变（FGFR3+）的患者达成100%的疾病控制率（DCR）。截至2024年8月15日，SURF301研究的1期部分共入组41名mUC患者，患者可携带或不携带FGFR3突变，且包括曾接受获批FGFR抑制剂erdafitinib治疗的患者。入组患者之前接受过大量治疗，其中44%患者在接受TYRA-300之前已接受了≥3线治疗，76%的带有FGFR3变异的mUC患者接受了≥3线治疗。分析显示，在接受每日一次≥90 mg剂量的FGFR3+ mUC患者中，TYRA-300在所有患者中均表现出抗肿瘤活性： 11名接受每日一次≥90 mg剂量的患者中，6人（54.5%）达到部分缓解（PR），其中3人缓解仍在持续。 10名接受每日一次90 mg剂量的患者中，5人（50%）达到PR。 1名接受每日一次120 mg剂量的患者中，1人（100%）达到PR。接受每日一次≥90 mg剂量的患者达成100%的DCR。截至数据截止日期，TYRA-300展示出良好的安全性特性。 TYRA-300是一种在研、口服、潜在“first-in-class”的FGFR3选择性抑制剂，旨在避免因抑制FGFR1、FGFR2和FGFR4所造成的毒性，并可抑制具有不同变异FGFR3的特性。该疗法目前正在开发用于治疗癌症及骨骼发育异常，包括软骨发育不全和侏儒症。 ▲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： [1] Tyra Biosciences Reports Interim Clinical Proof-of-Concept Data for TYRA-300, an Investigational Oral FGFR3-Selective Inhibitor, in Phase 1/2 SURF301 Study in Patients with Metastatic Urothelial Cancer (mUC). Retrieved October 27, 2024 from https://www.prnewswire.com/news-releases/tyra-biosciences-reports-interim-clinical-proof-of-concept-data-for-tyra-300-an-investigational-oral-fgfr3-selective-inhibitor-in-phase-12-surf301-study-in-patients-with-metastatic-urothelial-cancer-muc-302286685.html 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

临床结果临床2期

2024-10-28

·药明康德

“癌症之王”患者6个月生存率超90%的KRAS靶向小分子；疾病控制率达100%的FGFR3靶向疗法…… | 一周盘点

▎药明康德内容团队编辑本期看点 1. 口服选择性FGFR3靶向疗法TYRA-300的早期临床结果亮眼，接受剂量≥90 mg/天的FGFR3突变转移性尿路上皮癌（mUC）患者的疾病控制率（DCR）为100%。 2. 泛RAS抑制剂RMC-6236在经治胰腺导管腺癌（PDAC）患者中展现出令人鼓舞的抗肿瘤活性和安全性，携带任意RAS突变的PDAC患者在6个月的总生存率为91%。 3. 治疗转移性透明细胞肾细胞癌（ccRCC）的小分子HIF-2a抑制剂casdatifan在一项1/1b期临床试验中的DCR达81%。药明康德内容团队整理 TYRA-300：公布1/2期临床试验数据 Tyra Biosciences公司公布了其潜在“first-in-class”的口服疗法TYRA-300治疗转移性尿路上皮癌（mUC）患者的1/2期研究SURF301的数据。TYRA-300是一种FGFR3选择性抑制剂，旨在避免抑制FGFR1、FGFR2和FGFR4时产生的毒性，且无论是否存在与耐药性相关的FGFR3门卫（gatekeeper）突变都能发挥作用。截至2024年8月15日的数据，接受剂量≥90 mg/天的FGFR3突变mUC患者的DCR为100%，54.5%（6/11）的患者达到部分缓解（PR），其中3例仍在治疗中，接受90 mg/天剂量的患者中有50%（5/10）达到PR。安全性方面，TYRA-300的耐受性总体良好，FGFR2和FGFR1相关毒性不常见。 RMC-6236：公布1/1b期临床试验数据 Revolution Medicines公司宣布，其在研泛RAS抑制剂RMC-6236在经治胰腺导管腺癌患者中展现出令人鼓舞的抗肿瘤活性和安全性。RMC-6236是一款口服、可靶向突变和野生型RAS在GTP结合（具活性，ON）状态下的选择性抑制剂。此次公布的1/1b期多中心、开放标签、剂量递增和剂量扩展研究RMC-6236-001旨在评估RMC-6236作为单药治疗携带RAS突变或野生型RAS晚期实体瘤患者的效果。结果显示，RMC-6236单药作为二线疗法可改善携带任意RAS突变PDAC患者的中位无进展生存期（PFS）与总生存期（OS）。在二线治疗中，携带KRAS G12X突变（KRAS G12X指的是KRAS蛋白第12位的甘氨酸因为基因突变，转换成其它氨基酸）的PDAC患者的中位PFS为8.5个月，中位OS为14.5个月。携带任意RAS突变的PDAC患者在二线治疗中的中位PFS为7.6个月，中位OS为14.5个月。携带KRAS G12X突变与携带任意RAS突变的PDAC患者在6个月时的总生存率分别为89%与91%。在二线治疗组中，携带KRAS G12X突变患者的客观缓解率（ORR）为29%，在三线及以上治疗组（3L+）中为22%，这些患者的DCR分别为91%和89%。目前该疗法的3期临床试验RASolute 302正在进行中。 Casdatifan：公布1/1b期临床试验数据 Arcus Biosciences公司公布了其在研小分子HIF-2a抑制剂casdatifan治疗转移性透明细胞肾细胞癌的1/1b期临床试验数据。HIF-2a是一种致癌转录因子，参与多个器官和肿瘤中的氧感应。由于VHL通路的基因异常，ccRCC几乎普遍与HIF-2a失调有关。通过选择性抑制HIF-2a，casdatifan可使一系列涉及肿瘤增殖和存活、耐药性和血管生成的通路失效，从而导致癌细胞死亡。截至2024年8月30日的数据，中位随访时间为11个月。在100 mg每日剂量扩展队列（n=32）中，DCR达81%，ORR为34%（2个待确认的缓解），许多患者仍在接受治疗。安全性方面，casdatifan具有可接受且可管理的安全性。 ▲Casdatifan治疗ccRCC患者的1/1b期试验数据（图片来源：参考资料[7]） NX-5948：公布1a/1b期临床试验数据 Nurix Therapeutics公司公布其在研蛋白降解剂NX-5948在治疗复发/难治性华氏巨球蛋白血症（WM）患者的1a/1b期临床试验中的最新数据。NX-5948是一种口服、可穿越血脑屏障的小分子布鲁顿氏酪氨酸激酶（BTK）蛋白降解剂。Nurix此前报告称，NX-5948对一系列对现有BTK抑制剂耐药的肿瘤细胞系表现出高效的抑制活性，这对于经过大量前期治疗的B细胞恶性肿瘤患者群体尤为重要。截至2024年10月10日的数据，在9例可评估应答的患者中，7例患者（77.8%）出现客观缓解，两例患者病情稳定（22.2%）。所有7例缓解均在8周的首次评估中观察到，其中5例患者仍在接受治疗，2例患者的治疗时间超过一年。不论患者基线MYD88和CXCR4的突变状态如何，均观察到应答。 Bel-sar（AU-011）：公布1期临床试验数据 Aura Biosciences公司宣布，其在研病毒样偶联药物（VDC）bel-sar（AU-011）在治疗非肌层浸润性膀胱癌（NMIBC）患者的1期临床试验中获得积极早期数据。Bel-sar由靶向肿瘤表面表达的糖蛋白的类病毒颗粒（VLP）与可由光激活的细胞毒性药物偶联生成。它被设计为具有双重作用机制，既能诱导肿瘤细胞坏死，又能激发强大且持久的抗肿瘤免疫反应。该试验共纳入了13名患者，主要终点是评估bel-sar单独使用（n=5）和bel-sar结合光激活（n=8）局部给药的安全性和可行性。次要终点是评估生物活性及肿瘤微环境（TME）中的免疫介导变化。13名研究参与者中，10名为低级别疾病患者，另外3名为高级别疾病患者。在接受bel-sar结合光激活治疗的患者（n=8）中，5名低级别疾病患者中有4名在组织病理学评估中显示无肿瘤细胞残留，达到了临床完全缓解（CR）。3名高级别疾病患者中有2名在膀胱镜检查中显示肿瘤明显缩小。 ONCT-534：公布1/2期临床试验数据 Oncternal Therapeutics公司公布了其在研雄激素受体（AR）抑制剂ONCT-534治疗复发性或难治性转移性去势抵抗性前列腺癌（mCRPC）患者的1/2期研究的最新数据。ONCT-534在前列腺癌模型中对未发生突变的AR以及多种形式的AR突变和异常都具有活性。ONCT-534具有治疗对AR通路抑制剂耐药（包括AR扩增、AR配体结合域突变或AR配体结合域缺失型剪接变体）的mCRPC患者的潜力。截至2024年9月30日的数据，每天两次的给药方案耐受性良好，没有出现与治疗相关的3级或更高级别的毒性反应。1名患者在接受每日两次160 mg剂量ONCT-534治疗后，前列腺特异性抗原（PSA）升高，但在随后4周以每日两次300 mg剂量ONCT-534治疗后，PSA下降了50%，同时计算机断层扫描（CT）显示与基线相比，靶病灶减少了16%。循环肿瘤细胞（CTCs）的计数和生物标志物分析显示，在另外6名患者中，ONCT-534对AR调控基因的表达和AR的核转位有令人鼓舞的效果。 Lunresertib+camonsertib：公布1期联合治疗试验数据 Repare Therapeutics公司公布了1期临床试验MYTHIC的最新数据，该试验评估了其PKMYT1抑制剂lunresertib和口服小分子ATR抑制剂camonsertib（lunre+camo）的组合疗法。在这项分析中，Repare公司对接受2期段推荐剂量（RP2D）的患者进行了约9个月的随访。结果显示，lunre+camo在保持临床疗效的同时，成功地减轻了与抗肿瘤药物机制相关的贫血。此外，在这些患者中未观察到任何级别的血小板减少或严重的中性粒细胞减少。 ATX-559：IND申请获得FDA许可 Accent Therapeutics公司宣布美国FDA已批准其潜在“first-in-class”的DHX9抑制剂ATX-559的IND申请，可在实体瘤患者中开展1期研究，重点关注BRCA1/2缺陷的乳腺癌和微卫星不稳定性高（MSI-H）和/或错配修复缺陷（dMMR）的实体瘤，预计首例患者将在2024年第四季度接受给药。 DHX9是一种DNA/RNA螺旋酶，据报道在复制、转录、翻译、RNA剪接、RNA处理以及维持基因稳定性等方面发挥着重要作用，该酶是一个有吸引力的新肿瘤学靶点。ATX-559通过抑制DHX9可利用关键的肿瘤弱点，导致癌症特异性细胞死亡。 ▲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] Revolution Medicines Presents Updated Data from RMC-6236 Monotherapy Study in Patients with Advanced Pancreatic Ductal Adenocarcinoma. Retrieved October 23, 2024 from https://www.globenewswire.com/en/news-release/2024/10/23/2967583/0/en/Revolution-Medicines-Presents-Updated-Data-from-RMC-6236-Monotherapy-Study-in-Patients-with-Advanced-Pancreatic-Ductal-Adenocarcinoma.html [2] Multiple Clinical Complete Responses Demonstrated Following Single Low Dose Administration of Bel-sar in Patients with Non-Muscle-Invasive Bladder Cancer (NMIBC) in Ongoing Phase 1 Trial. Retrieved October 18, 2024, from https://ir.aurabiosciences.com/news-releases/news-release-details/multiple-clinical-complete-responses-demonstrated-following [3] Oncternal Therapeutics Announces Updated Safety and Efficacy Data for Phase 1/2 Study of ONCT-534 for the Treatment of R/R Metastatic Castration-Resistant Prostate Cancer. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/22/2967000/0/en/Oncternal-Therapeutics-Announces-Updated-Safety-and-Efficacy-Data-for-Phase-1-2-Study-of-ONCT-534-for-the-Treatment-of-R-R-Metastatic-Castration-Resistant-Prostate-Cancer.html [4] Nurix Therapeutics Presents Positive Results from the Ongoing Clinical Trial of Its BTK Degrader NX-5948 in Patients with Relapsed/Refractory Waldenstrom’s Macroglobulinemia. Retrieved October 21, 2024, from https://www.globenewswire.com/en/news-release/2024/10/19/2965795/0/en/Nurix-Therapeutics-Presents-Positive-Results-from-the-Ongoing-Clinical-Trial-of-Its-BTK-Degrader-NX-5948-in-Patients-with-Relapsed-Refractory-Waldenstrom-s-Macroglobulinemia.html [5] Repare Therapeutics Announces Updated Positive Safety and Tolerability Results from the Phase 1 MYTHIC Clinical Trial. Retrieved October 25, 2024, from https://ir.reparerx.com/news-releases/news-release-details/repare-therapeutics-announces-updated-positive-safety-and [6] Tyra Biosciences Reports Interim Clinical Proof-of-Concept Data for TYRA-300, an Investigational Oral FGFR3-Selective Inhibitor, in Phase 1/2 SURF301 Study in Patients with Metastatic Urothelial Cancer (mUC). Retrieved October 25, 2024, from https://www.callunapharma.com/wp-content/uploads/2024/01/Calluna_Pharma_Launch_PR.pdf [7] First Clinical Data for Arcus Biosciences’ HIF-2a Inhibitor, Casdatifan, Showed Promising Clinical Activity and Tumor Shrinkage in Patients with Metastatic Kidney Cancer. Retrieved October 25, 2024, from https://investors.arcusbio.com/investors-and-media/press-releases/press-release-details/2024/First-Clinical-Data-for-Arcus-Biosciences-HIF-2a-Inhibitor-Casdatifan-Showed-Promising-Clinical-Activity-and-Tumor-Shrinkage-in-Patients-with-Metastatic-Kidney-Cancer/default.aspx [8] Interius BioTherapeutics Doses First Patient with in vivo Chimeric Antigen Receptor (CAR) Gene Therapy for B-cell Malignancies. Retrieved October 25, 2024, from https://interiusbio.com/2024/10/interius-biotherapeutics-doses-first-patient-with-in-vivo-chimeric-antigen-receptor-car-gene-therapy-for-b-cell-malignancies/ [9] Spur Therapeutics Showcases Positive New Data from Phase 1/2 GALILEO-1 Trial of FLT201, Its Novel Gene Therapy Candidate for Gaucher Disease, in Oral Presentation at ESGCT 31st Annual Congress. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/23/2967469/0/en/Spur-Therapeutics-Showcases-Positive-New-Data-from-Phase-1-2-GALILEO-1-Trial-of-FLT201-Its-Novel-Gene-Therapy-Candidate-for-Gaucher-Disease-in-Oral-Presentation-at-ESGCT-31st-Annua.html [10] Find Therapeutics Announces First Subject Dosed in Phase 1 Clinical Study of FTX-101. Retrieved October 25, 2024, from https://www.prnewswire.com/news-releases/find-therapeutics-announces-first-subject-dosed-in-phase-1-clinical-study-of-ftx-101-302278520.html [11] Zymeworks Announces First Patient Dosed in Phase 1 Clinical Trial Evaluating ZW171 in Advanced Mesothelin-Expressing Cancers. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/21/2966023/0/en/Zymeworks-Announces-First-Patient-Dosed-in-Phase-1-Clinical-Trial-Evaluating-ZW171-in-Advanced-Mesothelin-Expressing-Cancers.html [12] Aligos Therapeutics Announces U.S. FDA Clearance of IND Application for ALG-000184. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/22/2966892/0/en/Aligos-Therapeutics-Announces-U-S-FDA-Clearance-of-IND-Application-for-ALG-000184.html [13] Pierre Fabre宣布在PFL-002/VERT-002的I/II期首次给药，这是一种MET改变的NSCLC靶向治疗. Retrieved October 25, 2024, from https://www.prnasia.com/story/465694-1.shtml [14] Inozyme Pharma Announces Positive Interim Data from Phase 1 SEAPORT 1 Trial of INZ-701. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2968997/0/en/Inozyme-Pharma-Announces-Positive-Interim-Data-from-Phase-1-SEAPORT-1-Trial-of-INZ-701.html [15] Apogee Therapeutics Announces Results Up to 9 Months from Phase 1 Trial of APG777, its Novel Half-Life Extended Anti-IL-13 Antibody for the Treatment for Atopic Dermatitis and Other Inflammatory Diseases. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2968646/0/en/Apogee-Therapeutics-Announces-Results-Up-to-9-Months-from-Phase-1-Trial-of-APG777-its-Novel-Half-Life-Extended-Anti-IL-13-Antibody-for-the-Treatment-for-Atopic-Dermatitis-and-Other.html [16] BridgeBio Shares Positive Data from High Dose Cohort of Phase 1/2 CANaspire Study of Gene Therapy BBP-812 for Canavan Disease at ESGCT 2024. Retrieved October 25, 2024, from https://www.globenewswire.com/news-release/2024/10/24/2968601/0/en/BridgeBio-Shares-Positive-Data-from-High-Dose-Cohort-of-Phase-1-2-CANaspire-Study-of-Gene-Therapy-BBP-812-for-Canavan-Disease-at-ESGCT-2024.html [17] Precision BioSciences Receives First Approval of Clinical Trial Application to Initiate PBGENE-HBV First-In-Human Study for the Treatment of Chronic Hepatitis B. Retrieved October 25, 2024, from https://investor.precisionbiosciences.com/news-releases/news-release-details/precision-biosciences-receives-first-approval-clinical-trial [18] First Patients Dosed in Phase 1 Clinical Study of ImmunityBio’s CAR-NK Cell Therapy for the Treatment of Relapsed B-Cell Non-Hodgkin Lymphoma. Retrieved October 25, 2024, from https://ir.immunitybio.com/news-releases/news-release-details/first-patients-dosed-phase-1-clinical-study-immunitybios-car-nk?field_nir_news_date_value[min]= [19] Aprea Therapeutics Presents Preliminary Findings on Oral WEE1 Inhibitor APR-1051 at EORTC-NCI-AACR International Conference on Molecular Targets and Therapeutics. Retrieved October 25, 2024, from https://ir.aprea.com/news-releases/news-release-details/aprea-therapeutics-presents-preliminary-findings-oral-wee1 [20] Autolus Therapeutics Presents Clinical Data Update at the 2024 Lymphoma, Leukemia & Myeloma Congress. Retrieved October 25, 2024, from　https://www.globenewswire.com/news-release/2024/10/16/2964125/0/en/Autolus-Therapeutics-Presents-Clinical-Data-Update-at-the-2024-Lymphoma-Leukemia-Myeloma-Congress.html [21] Accent Therapeutics Announces FDA Clearance of IND Application for ATX-559, a First-In-Class Oral DHX9 Inhibitor. Retrieved October 25, 2024, from　https://www.prnewswire.com/news-releases/accent-therapeutics-announces-fda-clearance-of-ind-application-for-atx-559-a-first-in-class-oral-dhx9-inhibitor-302285845.html [22] Calluna Pharma launches and announces EUR 75 million Series A financing to develop novel therapies for inflammatory and fibrotic diseases. Retrieved October 25, 2024, from　 https://www.businesswire.com/news/home/20241023939388/en/Calluna-Pharma-Successfully-Completes-Phase-1-Clinical-Study-of-CAL101-a-First-in-Class-Therapeutic-for-Fibrotic-and-Fibro-Inflammatory-Indications/#:~:text=Calluna%20Pharma%20Successfully%20Completes%20Phase%201%20Clinical%20Study,CAL101%20is%20now%20entering%20Phase%202%20clinical%20development 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

临床结果基因疗法临床终止

2024-10-25

·Endpoints

Tyra's stock dips as it gives first look in challenge to J&J’s bladder cancer drug Balversa

Tyra Biosciences unveiled early trial results on its FGFR3-specific inhibitor in advanced bladder cancer patients on Friday, the public company’s first presentation of human data since its inception in 2018. The biotech’s data were highly anticipated: Its shares $TYRA were up over 100% ahead of the readout, but they fell 18% Friday morning on the update. While the company tested a range of doses in the Phase 1 portion of its SURF301 study in metastatic urothelial carcinoma, its efficacy results focused on the patients who received at least 90 mg, where it believes the drug achieved “adequate target coverage.” Five of the 10 patients who received a 90 mg daily dose of TYRA-300 achieved a partial response, as did one patient who received a 120 mg dose. According to Tyra, three of those six responses are still ongoing. The company said 41 patients with FGFR3+ cancer have enrolled as of Aug. 15, including those who were previously treated with Johnson & Johnson’s Balversa. Tyra’s ultimate goal is to develop a safer treatment than Balversa, which in 2019 became the first FGFR-targeted drug to receive FDA accelerated approval for bladder cancer and earlier this year was granted full approval in advanced FGFR3+ urothelial carcinoma. In its confirmatory trial, Balversa resulted in a response rate of 35% in FGFR3+ advanced bladder cancers. TYRA-300, which goes only after FGFR3 while sparing other isoforms (FGFR1/2/4), aims to evade or lessen certain side effects including eye problems, mouth sores and inflammation, and increased phosphate levels. As we started to see a profile and hear from investigators that this was a really well-tolerated drug, we got really excited that the sparing of FGFR1 and 2 thesis could play out,” CEO Todd Harris said of the safety data in an interview with Endpoints News . The biotech said in a release that SURF301 patients experienced “infrequent FGFR2- and FGFR1-associated toxicities.” TD Cowen analyst Tyler Van Buren wrote in a note Friday that “TYRA-300 boasts a superior tolerability profile compared to pan-FGFR inhibitors,” like Balversa. In 15 patients at the 90 mg dose, the most common adverse events were liver enzyme increases and dry mouth, which 6 trial participants experienced. One grade 3 case of elevated liver enzyme levels resulted in treatment discontinuation and one grade 3 case of diarrhea was reported as a dose-limiting toxicity at 90 mg. “These data give us confidence to advance TYRA-300 through Part B in SURF301 and explore larger opportunities with Phase 2 studies in metastatic urothelial cancer, non-muscle invasive bladder cancer and achondroplasia,” said Tyra CEO Todd Harris in a statement. Harris told Endpoints News that for both non-muscle invasive bladder cancer and achondroplasia, a form of dwarfism, Tyra expects to test lower doses of TYRA-300 than the 90 mg it highlighted in urothelial carcinoma.

临床结果加速审批上市批准