Sunitinib Malate

2024 CMC（CRO&MAH&CMO）博览会，将于8月15-16日在苏州国际博览中心C、D、E馆召开，内容涵盖前沿法规政策、MAH、改良型新药、吸入制剂、透皮制剂、中药、缓控释制剂、注射剂、原料药、辅料领域热点话题。 一键报名 · 见证合作！ 这是呋喹替尼于2023年11月在美国上市以来获得的第二个全球头部市场的成功准入。 呋喹替尼是首个且唯一一个在欧盟获得批准用于治疗结直肠癌的针对所有三种VEGFR 亚型的选择性抑制剂。 6月22日，和黄医药对外宣布，其自主研发的抗肿瘤新药呋喹替尼（中文商品名：爱优特；英文商品名：FRUZAQLA）已取得欧盟委员会（European Commission）批准，用于治疗经治转移性结直肠癌。 这是继去年11月呋喹替尼“出海”美国后，再次获全球头部市场准入，又一款在美国和欧洲这两大全球主要市场都获批上市的创新药诞生。 呋喹替尼是一种选择性针对所有三种VEGFR的口服抑制剂。呋喹替尼此次在欧洲获批，主要是基于FRESCO-2国际多中心III期研究的结果，该研究的数据已在2023年6月发表于《柳叶刀(The Lancet)》。 据悉，FRESCO2研究达到了所有主要终点及关键次要终点，在总生存期（OS）和无进展生存期（PFS）方面均显示出达到具有统计学意义和临床意义的显著改善，并在接受呋喹替尼治疗的患者中展现出一致的获益，无论患者既往接受过何种治疗。 同时呋喹替尼表现出良好的安全性，在接受呋喹替尼联合最佳支持治疗的患者中，20%出现导致治疗停止的不良反应，而接受安慰剂联合最佳支持治疗的患者中，该比例为21%，二者大致相当。 呋喹替尼是由和黄医药自主研发的小分子酪氨酸激酶抑制剂，2018年9月呋喹替尼在中国获批上市，用于治疗转移性结直肠癌，并于2020年1月纳入国家医保目录。 2022年、2024年，呋喹替尼相继在中国澳门、中国香港上市。 目前，该药已覆盖全国328个城市、超过3000家肿瘤医院，市场销售额累计已超20亿元。 2023年1月，和黄医药先将主要产品呋喹替尼除中国内地、香港及澳门以外的全球权益授予了日本药企武田制药（Takeda）这笔交易的首付款为4亿美元，总额最高达11.3亿美元，一度刷新了当时中国小分子新药出海授权交易纪录。 2023年11月8日，呋喹替尼成功登陆美国市场，获美国食品药品监督管理局批准用于治疗经治转移性结直肠癌，获批后48小时内，即开出首张处方，并将首盒药物交到患者手中。 在获批后一周内，呋喹替尼即进入全世界最权威的治疗指南——美国国家综合癌症网络指南。 根据武田制药公布的数据，呋喹替尼在美国市场2024年第一季度的销售额已超5000万美元。 据悉，呋喹替尼在日本以及10余个全球其他地区的上市申请正在积极推进中，呋喹替尼二线治疗胃癌以及联合信迪利单抗用于治疗晚期子宫内膜癌的中国新药上市申请已进入国家药监局审评环节，有望于2024年惠及全球更多国家和地区的患者。 截至2024年5月，全球已获批上市的靶向VEGF/VEGFR的新药有29个，其中20个是小分子靶向药物。 其中，最早上市的小分子VEGF/VEGFR抑制剂如索拉非尼、舒尼替尼的全球销售峰值达超过10亿美元以上。 新一代的抗血管生成抑制剂仑伐替尼（原研）2022年全球销售额达到了19.06亿美元（仅卫材药业报表收入）。在中国，安罗替尼（原研及仿制药）近三年的销售额稳定在40亿人民币，可见抗血管生成抑制剂的潜在市场范围广，市场空间巨大。 有券商研报预测，呋喹替尼的全球销售峰值将超过100亿人民币。 推荐阅读

Encouraging signs of activity were observed, including a 23% objective response rate (ORR) across all patients (median four prior lines of therapy) and a 43% ORR across second-line patients Favorable tolerability pro observed, consistent with use in front-line and second-line settings Data to be highlighted in an oral presentation today at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting PLYMOUTH, Mass.--(BUSINESS WIRE)-- IDRx, Inc., a clinical-stage biopharmaceutical company dedicated to transforming cancer treatment with purpose-built precision therapies, today announced updated preliminary clinical data from the Phase 1 portion of the company’s ongoing StrateGIST 1 study of IDRX-42 in patients with advanced gastrointestinal stromal tumors (GIST). These data will be highlighted today in an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. IDRX-42 is a novel, KIT mutant-selective, tyrosine kinase inhibitor (TKI) that has potent activity against both the key activating mutations and broad coverage of the clinically relevant resistance mutations in KIT-driven GIST. IDRX-42 was designed to overcome the twin challenges of on-target treatment resistance and off-target driven adverse events, which limit the clinical benefit of currently available TKIs. “There is a significant unmet medical need for next-generation therapies for GIST patients. Current standards of care either lack the breadth of resistance mutation coverage necessary for patients to realize long durations of response or disease stabilization, or they lack selectivity, resulting in unwanted side effects, or both,” said Professor Patrick Schöffski, M.D., M.P.H., Head of the Department of General Medical Oncology at the University Hospitals Leuven. “These promising Phase 1 data support the potential of IDRX-42 to provide meaningful clinical benefit for GIST patients, with encouraging evidence of clinical activity in patients with activating KIT mutations in exons 9 and 11, as well as in patients with clinically relevant resistance mutations in KIT, importantly those in exons 13 and 17.” Updated Preliminary Clinical Data Summary As of the data cut-off date of April 28, 2024, 73 patients have been treated with IDRX-42 in the Phase 1 portion of the ongoing StrateGIST 1 trial across dose cohorts ranging from 120 mg once daily (QD) to 600 mg twice daily (BID). All 73 patients had KIT-mutant GIST. 66 patients were evaluable for efficacy as of the time of the data cut-off. Patients who were efficacy evaluable must have had at least 1 post-baseline tumor assessment or had clinical progression or death before the first post-baseline tumor assessment. While a maximum tolerated dose was not reached, dose escalation in the Phase 1 portion of the trial has completed, and the Phase 1b dose confirmation portion of the trial has been initiated utilizing a dose of 300mg tablet formulation, which is equivalent to the 400mg capsule formulation. Patients were heavily pretreated, with a median of four prior lines of therapy. 19% (14/73) patients had received one prior line of therapy. 11% (8/73) patients had received two prior lines of therapy. 70% (51/73) patients had received three or more prior lines of therapy. 74% of patients remained on study treatment, and the median duration of treatment was 16 weeks as of the data cut-off. 100% of second line patients remained on treatment as of the data cut-off. The objective response rate (ORR) by modified RECIST v1.1 in the efficacy evaluable population was 23% (15/66) treated across all lines of therapy, of which all were partial responses (12 confirmed PRs, 3 pending confirmation). The ORR across second line patients was 43% (6/14; 4 confirmed PRs, 2 pending confirmation). In analyses of circulating tumor DNA (ctDNA), reductions in mutant allele fraction were observed consistently across KIT mutations detected in baseline samples. Reductions in mutant allele fraction, including to undetectable levels, as best response were observed in exon 9 and 11 activating mutations, and in resistance mutations exon 13, 14, and 17. IDRX-42 exhibited a favorable safety pro treatment-related adverse events (TRAEs) were mainly low grade. The most frequently reported TRAEs (≥20%) were gastrointestinal symptoms (diarrhea, nausea, decreased appetite, vomiting, dysgeusia) and fatigue. Gastrointestinal adverse events were Grade 1 in most patients, when they occurred. A low rate of dose modifications due to TRAEs was observed at the 400mg QD dose level, with only 6% dose reductions, 9% dose interruptions, and 0% discontinuations due to TRAEs. Dose-limiting toxicities (DLTs) were observed in 3/73 patients at doses of 600 mg, 800 mg and 1200 mg, respectively. All 3 patients elected to reduce dose and remained on study as of the data cut-off (range: >3 to >11 months); 2 of these patients have achieved a confirmed PR at a reduced dose of 400 mg QD. A flat and dose-linear pharmacokinetic pro observed. “In this dataset, IDRx has presented preliminary proof-of-concept of IDRX-42 supporting its potentially best-in-class pro patients with GIST,” said Tim Clackson, Ph.D., Chief Executive Officer of IDRx. “Importantly, we believe these efficacy and safety data support our plan to move IDRX-42 rapidly into early lines of therapy, including second-line and front-line, where patients haven’t seen a new treatment option in over 15 years.” “We are excited for these data to be presented today, as they support all aspects of our target product profile, including evidence of potent activity against relevant activating and resistance mutations in KIT, combined with a favorable safety profile,” said David Kerstein, M.D., Chief Medical Officer of IDRx. “Across a wide dose range and in this heavily pre-treated patient population, promising signs of clinical activity have been observed, and the initial data compares favorably against approved therapies and those in clinical development. We are encouraged by the emerging safety and tolerability profile, characterized mainly by low grade, manageable gastrointestinal adverse events with a notable lack of adverse events generally associated with off-target activity, such as hand-foot skin reaction and hypertension, supporting the overall selectivity of the molecule. We would like to express our gratitude to the patients and investigators for their participation in the ongoing StrateGIST 1 study.” The Data Will be Highlighted in an Oral Presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting: Title: StrateGIST 1: A first-in-human (FIH), phase 1 study of IDRX-42 in patients with metastatic gastrointestinal stromal tumors resistant to prior treatment with tyrosine kinase inhibitors (TKIs) Presenter: Patrick Schöffski, M.D., M.P.H. Abstract Number: 11501 Presentation Type: Oral Abstract Session Session Title: Sarcoma (Sub Track Gastrointestinal Stromal Tumors) Time: 3:12 P.M. CDT About GIST Gastrointestinal stromal tumors (GIST) are the most common subtype of soft tissue sarcoma. Approximately 80% of cases arise from gain of function mutations in the KIT receptor tyrosine kinase, driving the malignancy through constitutive activation of aberrant signaling. Resistance mutations in KIT emerge in ~90% of patients treated with imatinib, the current standard of care for GIST. In unresectable or metastatic GIST, clinical benefits from existing treatments can vary by mutation type. About the StrateGIST 1 Study StrateGIST 1 is an ongoing, open-label, first-in-human Phase 1/1b study designed to evaluate the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of IDRX-42 in patients with metastatic and/or surgically unresectable GIST after failure of imatinib and other approved drugs. The study is currently enrolling patients with documented pathogenic mutation in KIT or any platelet-derived growth factor receptor alpha (PDGFRA) mutation (other than PDGFRA exon 18) at sites in the U.S., Belgium, Germany and Spain. The Phase 1b portion will include expanded exploratory cohorts based on defined lines of prior TKI therapy. About IDRX-42 IDRX-42 is a potent, oral, highly selective KIT inhibitor targeting all major categories of activating and resistance mutations in patients with KIT-mutant GIST (including variants in exons 9, 11, 13 and 17). In preclinical studies, IDRX-42 demonstrated superior antitumor activity compared to imatinib, the current first-line of therapy, in GIST human xenograft models expressing mutations in KIT exons 9 and 11. In xenograft models expressing secondary resistance mutations in KIT exon 13 or 17, IDRX-42 treatment resulted in potent and dose-dependent antitumor activity superior to the second-line standard of care agent, sunitinib. IDRX-42 is currently being evaluated in a first-in-human Phase 1/1b study. About IDRx IDRx is a clinical-stage biopharmaceutical company dedicated to transforming cancer care with intelligently designed precision therapies. IDRx aims to address the limitations of today’s precision cancer medicines with highly potent and selective targeted therapies to stop key tumor escape mechanisms and prolong response to therapy. IDRx’s lead program is IDRX-42, designed to inhibit key genetic drivers and drug-resistant mutations of KIT in gastrointestinal stromal tumor (GIST). IDRx's pipeline also includes a second KIT inhibitor, IDRX-73. Founded in 2021, IDRx’s leadership team has extensive experience in drug development and collectively has been involved in the discovery, development, and commercialization of more than 10 approved medicines. To learn more, please visit and follow us on LinkedIn. View source version on businesswire.com: Contacts 1AB Katie Engleman katie@1abmedia.com Source: IDRx, Inc. View this news release online at: