III期研究ASC4FIRST达到双主要终点，结果具有临床意义和统计学显著性：Scemblix®在第48周的MMR率比研究者选择的标准治疗TKI（伊马替尼、尼洛替尼、达沙替尼和博舒替尼）（67.7% vs. 49.0%）和伊马替尼（69.3% vs. 40.2%）都更优1。
研究中，Scemblix还展示了比伊马替尼和二代TKI良好的安全性和耐受性，更少的3级以上AE和剂量调整事件及不良事件导致的治疗终止1。
尽管TKI已经改变了CML的治疗，但未满足的需求仍然存在；许多新诊断的患者未能达到分子学反应目标，并且许多人由于耐受性问题而中断或改变治疗2-17。
Scemblix已获得美国FDA突破性疗法认定且正在FDA审评中；相关数据于ASCO 的最新突破性研究中发布，还将在EHA最佳摘要环节发表口头报告。该研究结果已在《新英格兰医学杂志》（NEJM）同步发表，这是Scemblix第4篇NEJM发表的研究，也是自2012年后唯一在CML有NEJM发表的产品。
近日，诺华在2024年美国临床肿瘤学会（ASCO）年会上发布了关键性III期ASC4FIRST研究的积极结果：Scemblix®治疗新诊断费城染色体阳性慢性髓性白血病慢性期（Ph+ CML-CP）患者在第48周显示出比研究者选择的酪氨酸激酶抑制剂（TKI）（伊马替尼、尼洛替尼、达沙替尼和博舒替尼）和单独伊马替尼都更优的主要分子学反应（MMR）率1。Scemblix在第48周的MMR率比二代 TKI（尼洛替尼、达沙替尼和博舒替尼）的比率数值更高1。此外，Scemblix表现出良好的安全性和耐受性，相对于伊马替尼和二代TKI，不良事件（AE）和治疗中断更少1。
南澳大利亚健康与医学研究所（SAHMRI）教授Tim Hughes医学博士：“Scemblix是第一个有头对头研究支持在疗效上优于研究者选择的标准治疗TKI的CML治疗药物，当你将Scemblix的疗效与安全性及耐受性结合起来时，我们有了一个潜在的、有前景的一线治疗选择，来帮助新诊断患者实现他们的治疗目标。”
Scemblix和研究者选择的标准治疗TKI的中位随访时间分别为16.3个月和15.7个月1。Scemblix治疗组患者第48周的MMR应答率比研究者选择的标准治疗TKI组高近20%，比伊马替尼组高近30%1。使用Scemblix治疗的患者在更深分子学反应（MR4和MR4.5）的达成率上也比研究者选择的标准治疗TKI和单独伊马替尼更高1。
a 所有接受Scemblix （n=201）或研究者选择的TKI （n=204）的患者。基于随机前选择TKI和EUTOS长期生存（ELTS）风险组进行调整后的治疗差异。
b 203名患者在随机前选择伊马替尼分层中被随机分配接受Scemblix（n=101）或伊马替尼（n=102）。在基线ELTS风险组进行调整后的治疗差异。
c 202名患者在随机前选择二代TKI分层中被随机分配接受Scemblix（n=100）或二代TKI（n=102：尼洛替尼, 48%; 达沙替尼, 41%; 博舒替尼, 11%）。
d 次要终点的统计学显著性未经过效能计算。
在新诊断患者中，Scemblix的安全性与既往注册研究一致，未观察到新的安全问题1。相对于伊马替尼和二代TKI，Scemblix组报告的≥3级AE、因AE导致剂量调整或因AE导致治疗终止的发生率均更低1。
诺华药品开发总裁兼首席医学官Shreeram Aradhye医学博士：“CML患者需要有效且耐受性良好的治疗方案，以获得长期有意义的临床结局。令人信服的ASC4FIRST数据突出表明，Scemblix有可能在初诊成人患者中取得优于标准疗法的治疗结果，同时有望保持良好的安全性和耐受性。这些研究结果再次证明Scemblix是一种经证实的Ph+CML-CP治疗方法，我们也将在过去20年来的CML创新积淀的基础上不懈努力。”
CML照护者、患者权益倡导人士兼CML倡导者网络指导委员会财务主管Gerald Clements：“鉴于CML的长期管理，副作用对患者来说是一个挑战。它们影响患者的日常生活、导致高比例的治疗方案转换，长期可耐受的有效管理是一个重要的未满足需求。如果能在合适的患者首次诊断时使用Scemblix，他们可能有机会在起初就接受高效治疗，同时维持有质量的日常生活。”
该研究仍在进行中，下一次的数据读取计划在第96周进行，评估关键次要终点（第96周的MMR）以及其他次要终点18。
Scemblix基于48周数据结果第三次获得FDA突破性疗法认定。这些数据也将在2024年6月的欧洲血液学协会（EHA）年会上以全体会议形式对外公布。
关于III期临床研究ASC4FIRST
ASC4FIRST (NCT04971226) 是一项比较口服Scemblix® 80 mg QD与研究者选择的TKI（伊马替尼、尼洛替尼、达沙替尼或博舒替尼）的III期、多中心、头对头、随机开放研究，共纳入405例新诊断Ph+CML-CP成人患者18。该研究的两个主要终点是根据第48周达到MMR的患者比例，分别比较（1）Scemblix与研究者选择的TKI的疗效和（2）Scemblix与伊马替尼（随机分组前研究者选择的TKI为伊马替尼的患者组）的疗效18。
研究仍在进行中，关键次要终点为第96周时达到MMR的患者比例，安全性终点为第96周时至因不良事件终止研究治疗的时间18。该研究还评估了其他次要安全性和疗效终点，包括在所有计划数据采集时间点和截至这些时间点的MMR、MR4、MR4.5、完全血液学缓解（CHR）和BCR:ABL1 ≤ 1%；首次达到MMR、MR4和MR4.5的时间和持续时间；至治疗失败的时间；无事件生存期、无失败生存期，无进展生存期和总生存期18。
关于Scemblix®
Scemblix® 是目前首个通过特异性靶向ABL肉豆蔻酰口袋（STAMP抑制剂）的CML治疗药物19-21。目前已批准的药物是靶向ATP结合位点的TKI21。
Scemblix已在包括美国和欧盟在内的70多个国家获得批准，用于治疗既往接受过两种或两种以上TKI治疗的成人Ph+CML-CP患者22-24。在包括美国在内的一些国家，Scemblix也获批用于治疗具有T315I突变的Ph+CML-CP患者23-25。
Scemblix是TKI耐药和/或不耐受患者的一种重要的治疗选择2-17，对其作为单药和联合方案在多线治疗Ph+CML-CP的研究正在进行中18-20,24,26–38,18-20,24,26-38。
关于诺华对CML的承诺
诺华为CML患者做出了长期的科学承诺。20多年来，我们的科学技术大胆创新，帮助许多患者将CML转变为慢性疾病。尽管取得了这些进展，但我们并没有停下。我们继续研究针对该疾病的方法，为许多患者因治疗耐药和/或不耐受而面临的挑战寻求解决之道。我们的传统激励着我们不断创新——我们继续在开发新药方面引领潮流，以解决CML的未满足需求。诺华还致力于为患者提供可持续的治疗以及与全球CML社区合作，继续重新规划CML的治疗。我们与Max基金会的合作开始于20多年前，提供了格列卫，达希纳和现在的Scemblix的可及，并在低中收入国家产生了巨大的影响，迄今为止支持了100,000名患者。
参考文献
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