Defactinib

关注无癌家园 我们战癌到底 癌症，这个烦恼了人类几千年的麻烦，时至今日都没得到很好的解决，癌症这个词仿佛也成了死亡与恐惧的代名词。在人类与癌症搏斗的无声战役中，历经无数探索走到现在虽初有成绩，但远未达终点。 然而，值得庆幸的是，仍然有些患者已经被临床治愈、保持无癌甚至带瘤生存多年！ 无癌家园小编曾经看过一句鼓舞人心的话，所谓幸存者，不是存活了多久，而是不被癌症打垮、吞噬。近日，美国癌症研究协会（AACR）发布了最新癌症进展报告，报告中总结了在过去1年里癌症治疗最值得关注的新药新技术，其中不乏官网上公布的癌症幸存者的治疗故事。无癌家园小编为了给各位癌友们加油打气，熟悉目前前沿重磅的新药新技术，特意整理出来，以供各位参考。 图源摄图网（已授权） 63%肿瘤消退！31岁设计师绝境逢生，新型TCR-T细胞疗法创下生命奇迹 三年前，31岁的奎因·约翰森还觉得人生尽在掌握。作为多伦多一名事业有成的工业设计师，他和相爱近十年的伴侣凯特，享受着都市生活的一切美好——探索新餐厅，规划着充满希望的未来。然而，2021年初一阵挥之不去的疲惫感，像一记闷棍，敲碎了他平静的生活。 他走进多伦多西部医院，本以为只是劳累过度，却接到了犹如晴天霹雳的诊断：他因严重失血而生命垂危，血红蛋白水平低至危险值。更可怕的是，扫描结果显示他的胃部有一个正在出血的肿瘤。最终，活检确诊为滑膜肉瘤——一种专盯年轻人的、罕见且凶险的癌症。 几周之内，奎因的世界天翻地覆。输血、放疗、紧急化疗……“有人把癌症硬塞进你的生活，这感觉真是毁灭性的，”奎因回忆道。更雪上加霜的是，那时正值新冠疫情末期，严格的探视制度让他只能在孤独中面对恐惧：“我在医院里，很难见到家人，那感觉更加孤独。” 从2021年3月开始，他踏上了炼狱般的标准治疗之路：6个周期的化疗，每个周期是4天住院输液和2周痛苦恢复的循环。副作用吞噬了他的一切。“我当时才31岁，凯特也31岁——我们本该好好生活的。”命运再次作弄，第四轮化疗刺穿了他的胃壁，导致他不得不禁食两个月，全靠静脉注射维持生命，在隔离病房里与感染和绝望作斗争。 尽管化疗重创了他的身心，但它确实起效了——肿瘤显著缩小，使得医生得以成功切除了他部分胃部。此后两年，奎因享受着来之不易的“无癌”生活，以为噩梦已经结束。 然而，2024年6月的一次常规扫描，带来了复发转移的坏消息。这意味着，常规手段已无法治愈他。就在希望似乎再次熄灭时，一扇新的门打开了——他的医生提到了一个名为 afamitresgene autoleucel（简称afami-cel） 的临床试验。这是一种尖端的TCR-T细胞免疫疗法，能像“活体药物”一样，改造患者自身的免疫细胞，让其精准追杀癌细胞。 幸运的是，奎因体内存在的两种罕见蛋白质生物标志物（HLA-A02和MAGE-A4），让他成为了这场“顶级定制疗法”的天选之人。在与时间赛跑中，他成功搭上了试验的末班车。 2024年9月，奎因接受了为期一周的“预备化疗”后，住院5天，输注了那份为他量身定制的“细胞大军”。与化疗的痛苦截然不同，这次治疗他几乎没有任何严重副作用。“住院的4天很悠闲，这很棒。能感到‘无聊’，真是太棒了，”他幽默地说。 奇迹，在随后的CT扫描中一次次被证实：肿瘤持续缩小，最新扫描显示缩小了惊人的63%！ 如今，奎因的医生用“稳定”来形容他的病情。“我们的谈话内容变了，”奎因的语气中充满了希望，“我们不再讨论如何应对下一个危机，而是如何继续我的生活。”他已经重返全职工作，和凯特重新开始规划未来。 他的主治医生指出，afami-cel是一次真正的范式转变，是首次将基因工程T细胞成功用于实体瘤治疗。“当我们观察到疗效时，这种疗效可能是深远的、有意义的，而且持续时间很长。”奎因，就是这一切最生动的证明。 官宣！全球首款TCR-T细胞疗法获FDA批准上市！ 2024年8月2日，国际医学领域传来一则振奋人心的消息！专门采用针对MAGE-A4癌症抗原的TCR-T技术Afami-cel（以前称为ADP-A2M4）正式获得美国FDA批准上市，同时也有了自己响当当的大名——TECELRA®，这是全球首款针对于实体肿瘤的TCR-T疗法，用于治疗晚期滑膜肉瘤。然而，目前美国这款一次性细胞治疗的标价为727,000 美元（约520万人民币）堪称“天价”，成为暨120万一针的CAR-T,370万一针的TIL之后，目前最昂贵的癌症免疫疗法！ 截图源自businesswire官网 Afami-cel获批用于治疗已接受过化疗且患有某些HLA类型的晚期 MAGE-A4+ 滑膜肉瘤成人患者，也是首款TCR-T疗法，具有重要的里程碑意义。值得一提的是，这也是十多年来治疗滑膜肉瘤的首个有效疗法。 TCR-T的成功应用要追溯到2006年，Rosenberg小组在《Science》上发表的一篇文章中显示，经基因修饰的TCR-T细胞在黑色素瘤的治疗中显示了较好的应用前景——参与试验的17名患者中，有2人出现了抗肿瘤响应，这次研究首次证明TCR-T对实体瘤显示出巨大的潜力。 TCR-T技术主要机制是向普通T细胞中引入新的基因，使得改造过的T细胞能够表达有效识别肿瘤细胞的TCR（T cell receptor，T细胞抗原受体），从而引导T细胞杀死肿瘤细胞。 作为近年来的研究热点，TCR-T疗法目前在国内外正处于如火如荼的临床验证阶段，尤其是在实体瘤方面取得的成绩可谓是大放异彩。国内大部分企业已经进入研究者发起的临床研究（IIT）或早期临床阶段，目前最快已经推进到2期临床阶段。在适应症方面，针对肝癌、宫颈癌、软组织肉瘤的产品较多。对于实体瘤领域，TCR-T疗法挑战与机遇并存。 相关文章：520万一针的TCR-T细胞疗法能攻克癌症吗？国研多款临床试验瞄准肝癌、宫颈癌等！ 目前无癌家园有多项TCR-T疗法的临床试验正在进行招募，想要参加的患者可以拨打无癌家园医学部（400-626-9916）了解详细入排标准。 急招以下癌种： 1.至少一线治疗失败的食管鳞癌（含胃-食管交界部鳞癌）、滑膜肉瘤、卵巢癌、鳞状非小细胞肺癌 2.靶向KRAS G12V突变的结直肠癌、胰腺癌、肺腺癌等实体瘤； 此外，若想咨询其他细胞疗法（CAR-T、NK、CAR-NK、CTL、TILs等疗法）的患者，同样可将病理报告及治疗经历、出院小结等资料提交至无癌家园医学部，详细评估病情。 完成40个疗程，肿瘤全部消失！36岁妈妈揭秘抗癌新武器ADC药物 米歇尔·安德森-本杰明，一位纽约的医疗保健管理员和两个孩子的母亲，一直是家人和朋友的坚实依靠。她是那种习惯掌控局面、为他人奔走呼号的强者。然而，2020年9月，一纸诊断书将她从“支柱”变成了“患者”：36岁的她，患上了I期三阴性乳腺癌（TNBC）——一种极具侵袭性、尤其“青睐”年轻黑人女性的癌症。 一切的序幕，始于新冠疫情封锁期间。在家远程工作和教育孩子的米歇尔，发现自己右侧乳房莫名渗血。尽管初时医生怀疑是良性问题，但执着的她选择了深入检查。接下来的一周，节奏快得令人窒息：五次活检、一次核磁共振、一次外科咨询。面对可能到来的风暴，这位坚强的母亲说：“我希望我不会听到‘你得了癌症’，但我也做好了准备。” 当坏消息最终降临时，她只是短暂的心情悲伤。随后便调整状态，对医生说：“我们开始行动吧。”并开始研究罹患癌症的亚型、治疗方案和临床试验。“我需要用自己熟悉的方式去战斗。我不想让任何人来编造我的故事。” 她的抗癌之路布满了荆棘。初始的单侧乳房切除术后，她的身体两次排斥植入物，迫使她在化疗前就经历了九次手术。随后是艰苦的多轮AC-T化疗[包括阿霉素（阿霉素）、环磷酰胺和紫杉醇（紫杉醇）]，直到2021年5月，她终于“敲响钟声”，宣告阶段性胜利。 然而，命运的残酷在2022年10月再次显现。初次确诊两年后，癌症毫无征兆地卷土重来，且直接从I期跳至IV期转移性三阴性乳腺癌。“感觉就像爬了一级台阶，突然发现自己悬在了顶梁上。” 更绝望的是，常规的大门一扇扇对她关闭：她因缺乏特定的PD-L1生物标志物而无法接受免疫治疗，也因HER2阴性而无法使用靶向药。就在此时，一扇新的窗户打开了——一项名为德达博妥单抗（Datroway） 的抗体-药物偶联物（ADC）III期临床试验正在招募患者。米歇尔毫不犹豫地抓住了这根救命稻草。 这次选择，成为了她人生的转折点。如今，她已经完成了40个疗程的临床试验治疗，据信是该试验中疗程最多、疗效最好的患者之一。最新的扫描结果显示，她的体内已没有癌症迹象。 胜利的果实伴随着代价。治疗带来了严重的眼干、关节痛和口干等副作用。但米歇尔用钢铁般的自律予以回击：清淡饮食、服用维生素、练习瑜伽、举重训练、定期按摩。“除非我的杯子已经满了，否则我不会倾注于他人，”她坚定地说，“我计划成为这个圈子里最健康、最性感的40多岁女性。” ADC药物：精准抗癌的“生物导弹” 抗体偶联药物（ADC）是近年来肿瘤治疗领域的重大突破，被誉为“生物导弹”。这类药物由单克隆抗体、连接子和细胞毒性药物三部分组成，结合了靶向治疗和化疗的双重优势。 ADC药物通过抗体精准识别肿瘤细胞表面的特定抗原，将细胞毒性药物直接递送至肿瘤细胞内部。这种设计既提高了抗肿瘤效果，又显著降低了对正常细胞的毒副作用，实现了更精准的靶向治疗。 在HER2阳性乳腺癌领域，ADC药物已展现出革命性的治疗效果。Enhertu（T-DXd）作为第一代HER2-ADC，改变了晚期乳腺癌的治疗格局。而今，新一代HER2-ADC药物JSKN003的研发，将这一领域推向新的高度。 客观缓解率近55%！18.4个月持续缓解！JSKN003成乳腺癌新选择 JSKN003为靶向HER3与TROP2的双特异性抗体偶联药物（ADC）。此药通过二苯并环辛炔四肽连接子，与人源化双特异性抗体聚糖上的拓扑异构酶I抑制剂(TOP1i)相偶联。其能够精准地识别并结合HER2高表达的癌细胞，高效地将细胞毒性药物精准递送至肿瘤细胞内部，从而发挥强大的抗肿瘤作用。值得一提的是，JSKN003较同类ADC药物具有更好的血清稳定性、更强的旁观者杀伤效应，有效地扩大了治疗窗。 JSKN003在澳大利亚Ⅰ期临床研究和中国Ⅰ/Ⅱ期临床研究中治疗HER2阳性晚期乳腺癌的疗效与安全性。 数据显示：共纳入88例HER2阳性乳腺癌患者，在75例疗效可评估患者中，确认的客观缓解率（ORR）为54.7%，疾病控制率（DCR）和临床获益率（CBR）分别为94.7%和66.7%。 按治疗线数分析，既往接受一线治疗组15例患者ORR为66.7%，既往接受二线治疗组19例患者ORR为63.2%。 此外，还纳入了8例既往接受过T-DXd治疗的患者，其中7例具有可评估的疗效，1例达到部分缓解，4例疾病稳定，4例出现肿瘤缩小。 88例患者总人群的中位缓解持续时间（DoR）为18.4个月。截至数据截止日期，PFS尚未成熟，3个月和6个月PFS率分别为88.4%和75.4%。 详情请戳：抗癌新药井喷！EGFR、KRAS、NTRK等靶点迎来突破进展，这些肿瘤患者有药用了！ 目前无癌家园有多款ADC新药正在招募中！适用于疾病进展的晚期和/或乳腺癌、转移性卵巢癌、宫颈癌、胰腺癌、前列腺癌。 想要评估病情是否符合上述招募条件可将病理报告、治疗经历及出院小结等提交至无癌家园医学部400-626-9916进行初步评估！ 肿瘤完全消失！晚期卵巢癌教师亲历医学奇迹，两款靶向药缔造生命传奇 2019年，46岁的玛丽·凯瑟琳·莱利的生活画卷，充满了阳光与活力。作为伊利诺伊州的一名五年级特殊教育老师，是两个可爱孩子的母亲，她热爱徒步旅行、骑自行车、瑜伽和艺术创作，身体状况也一直很好。但当她开始出现持续性腹胀和尿频时，这一切发生了改变。 起初，她以为只是小问题。但2019年6月的妇科检查，超声波和OVA1检测结果异常，随后的CT扫描证实了她的卵巢上有一个肿块，很有可能是卵巢癌。“听到诊断结果，简直是毁灭性的，”玛丽回忆道，不祥的预感成真了。 幸运的是，在亲友的推荐下，她迅速联系上了其主治医生萨克，并且明确诊断为 卵巢癌III期，癌细胞已侵犯淋巴结。 手术前，恐惧笼罩着她。但萨克医生的冷静给了她力量。术后，她得知自己是低级别浆液性卵巢癌——它虽不如高级别类型凶猛，却极易复发，且当时缺乏成熟有效的疗法。 原本希望逃过化疗，但病理结果让她从2019年8月到11月，接受了6轮化疗。这位坚强的教师，把讲台变成了她的另一个战场。她将自己的治疗时间与学校日程完美对接，仅在化疗日才请假。 化疗后，她依靠雌激素阻断药阿那曲唑维持了三年稳定。然而，2023年，淋巴结的异常增大宣告了癌症的复发。 这一次，萨克医生为她指明了新的方向：一项针对avutometinib和defactinib两种靶向药的临床试验。尽管深知需要投入大量时间进行频繁检查，玛丽毫不犹豫：“如果有机会帮助我，我会去尝试。” 奇迹，在一年内发生了。她体内的癌细胞被完全清除，达到了“完全康复”。虽然皮疹、视力变化等副作用持续存在，但玛丽豁达地说：“是的，副作用确实很烦人。但我现在没有癌症，这很值得。” 她在这项为期两年的试验中，与医疗团队并肩作战，共同推进了这种曾无药可医的癌症的治疗进程。2025年5月，这对“黄金搭档”成功获得了FDA批准，而玛丽，也从试验参与者转为正式用药者。 如今，玛丽定期复查，依然无癌。她的孩子们在这场漫长的抗争中长大，女儿更是受她影响投身医学。他们为母亲参与改写医学史的试验而自豪。 好消息是，目前无癌家园有多款化疗药、靶向药、细胞疗法治疗卵巢癌的临床试验项目正在临床招募中，有意者可咨询无癌家园医学部（400-626-9916），详细评估病情。 从肺部“雇佣”免疫杀手：TIL细胞疗法如何为晚期癌患撕开一道光 2024年2月，律师理查德·施吕特收到了一个改变他人生的诊断结果：头颈部鳞状细胞癌。这位注重健康、坚持锻炼的三个孩子的父亲，生活瞬间崩塌。当理查德注意到嘴里有金属味，扁桃体上出现白色脓疱时，他意识到情况不对劲。 起初，医生对他的预后非常乐观，治愈率高达90%~95%。他接受了7周的化疗和质子治疗，满怀希望。然而，七月的一次扫描带来了致命打击：癌细胞已扩散至肺部和胸腔。目标从“治愈”变成了“姑息”，这结果真令人崩溃！ 为了求生，他们辗转全美顶尖医院，最终在美国国立卫生研究院（NIH）找到了希望——一项名为 TIL（肿瘤浸润淋巴细胞） 的尖端免疫疗法。这种疗法如同为他量身定制的“细胞大军”，能从他的肿瘤中提取免疫细胞，扩增后回输体内精准杀癌。 然而，希望近在咫尺时，一场意想不到的风暴袭来。NIH因预算削减裁员，导致本已准备好的治疗被延误。好在经过抗争，最终，在2025年7月24日，理查德开始了预备性化疗，并于8月1日成功接受了TIL输注，如今他正在积极地接受治疗，病情稳定。 免疫治疗新纪元，TILs疗法横空出世 肿瘤浸润淋巴细胞（TIL）治疗是一种过继细胞疗法（ACT），涉及从手术切除的癌症组织中分离出自体T细胞，在体外扩增和活化后重新输注到患者体内。 2011年，免疫治疗先驱Rosenberg团队在《Clinical Cancer Research》上发表了一项里程碑式研究：TILs治疗黑色素瘤患者的客观缓解率（ORR）达到56%，完全缓解率高达24%。这为TILs疗法的发展奠定了基础。 2024年2月16日，全球首款TIL疗法Lifileucel获得FDA加速批准，用于治疗PD-1抗体或BRAF抑制剂治疗失败的不可切除/晚期黑色素瘤。这吹响了细胞疗法攻克实体瘤的号角，也为肺癌等其他实体瘤的治疗带来新希望。 如何寻求TIL细胞治疗>> 目前无癌家园有TILs免疫细胞临床试验正在招募中，招募黑色素瘤、宫颈癌非小细胞肺癌、子宫内膜癌、乳腺癌，卵巢癌等实体瘤。 有意向的患者若想参加可整理出完整的病理报告、治疗经历、出院小结等再致电无癌家园医学部（400-626-9916），详细评估病情。 参加临床试验，选择更多治疗方案 由于我国临床试验起步晚，很多人对临床试验中的试药抱有偏见和不理解。其实在欧美国家很多患者会主动咨询医生是否有适合自己的临床试验。 在抗肿瘤新药不断更新的今天，很多患者通过参加临床试验获得了免费试用最新药物的机会，通过疗效更好的新药，获得了更长的生存获益和更多的治疗机会，对明确了获益机会的患者而言，临床实验可能是最佳的治疗选择。 为了让更多的癌症患者免费用到新型抗癌药物，无癌家园为广大病友提供免费入组临床试验的渠道，可以为癌症患者精准匹配最适合的临床试验，详情请咨询400-626-9916。 无癌家园提醒癌友们 国内细胞免疫治疗技术，包括CAR-T细胞（除上市的CAR-T外）、树突细胞疫苗、NK细胞、TILs细胞（除上市的TILs外）、TCR-T细胞（除上市的TCR-T外）、癌症疫苗等技术均处于临床试验阶段，未获准在医院正式使用。国内患者可以参加正规临床试验，在医生的监管下使用，无癌家园网不推荐患者冒然尝试任何医疗机构和研发机构的收费治疗。 无癌家园 抗癌资讯｜新技术｜新药研发｜权威专家 热门细胞疗法 细胞疗法相关文章 Review past  ▶▶▶ 1.8周肿瘤病灶完全消失！我国首例TILs疗法癌症治愈出现！国研多款疗法厚积薄发！ 2.肿瘤病灶接近完全缓解！NK细胞疗法联合化疗、靶向治疗晚期胰腺癌疗效惊艳！ 3.横扫33种癌症！最长生存期延长35个月！肿瘤免疫新贵γδT细胞主攻肺癌、肝癌等癌！ 4.肿瘤完全缓解！TILs细胞疗法竟能调动全身免疫军团对抗“红颜杀手”宫颈癌！ 5.370万天价TILs细胞疗法来袭！用自身免疫细胞杀灭实体瘤！手术前、标准治疗失败后更需关注！ 分享、收藏、点赞、在看安排一下？

TARGET-D 203 trial to evaluate VS-7375 both as monotherapy and in combination with cetuximab or panitumumab in previously treated metastatic colorectal cancer A cohort in TARGET-D 203 will also evaluate the combination of VS-7375 with cetuximab and chemotherapy for frontline treatment of metastatic colorectal cancer KRAS G12D is one of the most common KRAS variants in metastatic colorectal cancer, occurring in approximately 15% of patients All three TARGET-D registration-directed Phase 2 clinical trials now enrolling following first-patient dosing across pancreatic, colorectal, and lung cancers BOSTON--(BUSINESS WIRE)--Jul. 28, 2026-- Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today announced that the first patient has been dosed in the TARGET-D 203 Phase 2 registration-directed trial evaluating VS-7375, an investigational oral KRAS G12D (ON/OFF) inhibitor with best-in-class potential, to treat patients with KRAS G12D-mutated metastatic colorectal cancer (mCRC). The Company has now initiated treatment across all three of its TARGET-D registration-directed Phase 2 clinical trials evaluating VS-7375 in patients with KRAS G12D-mutated pancreatic, colorectal, and lung cancers. “KRAS G12D is the most common KRAS mutation found in colorectal cancer and is associated with a worse prognosis for patients compared with KRAS wildtype – underscoring the need for an FDA-approved treatment option specifically for KRAS G12D-mutated cancers. We believe VS-7375 with EGFR blockade has the potential to significantly improve outcomes for patients with KRAS G12D-mutated metastatic colorectal cancer due to its differentiated profile and encouraging preliminary data from our ongoing Phase 1/2 trial,” said Michael Kauffman, M.D., Ph.D., president of development at Verastem Oncology. “VS-7375 has demonstrated preliminary anti-tumor activity in combination with full dose cetuximab with no unexpected toxicities. Dosing the first patient in TARGET-D 203 marks an important milestone in our clinical development program as we continue to advance VS-7375 and build on the encouraging data generated to date.” TARGET-D 203 (NCT07659795) is a Phase 2, open-label, multi-center study to evaluate VS-7375 at 900 mg once daily (QD) both as monotherapy and in combination with anti-EGFR therapies, including cetuximab or panitumumab, in previously treated KRAS G12D-mutated mCRC. The study is also evaluating VS-7375 in combination with cetuximab and chemotherapy in the first line setting in patients with KRAS G12D-mutated mCRC. In June 2025, Verastem initiated TARGET-D 101, its Phase 1/2 dose escalation, dose expansion, and combination clinical trial evaluating the safety and efficacy of VS-7375 in patients with KRAS G12D-mutated metastatic pancreatic ductal carcinoma (mPDAC), mCRC, advanced non-small cell lung cancer (NSCLC), and other solid tumor cancers. In a recent update, the Company shared that VS-7375 demonstrated encouraging anti-tumor activity across multiple KRAS G12D-driven tumor types, including mPDAC, mCRC, and advanced NSCLC, with evidence of dose-dependent activity, favorable pharmacokinetics supporting target exposure, and a favorable and manageable safety and tolerability profile. Patient follow-up continues to mature across monotherapy and combination cohorts, and the Company expects to share an update in the second half of 2026. About Colorectal Cancer Colorectal cancer (CRC) is the third most common cancer and the second-leading cause of cancer-related death in the U.S. In 2026, an estimated 158,850 people will be diagnosed with colon and rectal cancer. CRC is increasingly affecting younger adults, with one in five new diagnoses now occurring in people younger than age 55, and patients diagnosed before the age of 50 are more likely to present with advanced or metastatic disease at diagnosis. Metastatic colorectal cancer (mCRC), or stage IV disease, occurs when the cancer spreads beyond the colon or rectum to distant organs. Approximately 50% of colorectal cancer cases harbor KRAS mutations, with KRAS G12D accounting for approximately 15% of all CRC cases. Despite advances in the treatment of mCRC, there has been minimal progress in the treatment of patients with KRAS G12D-mutated disease, and no therapies targeting KRAS G12D have been approved for this patient population. Survival outcomes remain poor, underscoring the need for new and improved treatment options. About KRAS G12D KRAS G12D represents 26% of all KRAS mutations, making it the most prevalent KRAS mutation in human cancers. When the KRAS gene is mutated, it can promote cancer development and growth. Patients with KRAS G12D-mutant tumors often have poorer outcomes, underscoring the need for therapies designed specifically to inhibit this mutation potently and for a long duration. The KRAS G12D mutation occurs most commonly in pancreatic (40%), colorectal (15%), endometrial (8%), biliary tract (7-15%), and non-small cell lung (5%) cancers. Currently, no therapies are approved by the U.S. Food and Drug Administration (FDA) specifically targeting KRAS G12D mutations in cancer. About VS-7375, an Oral KRAS G12D (ON/OFF) Inhibitor & TARGET-D Clinical Program VS-7375 is a potential best-in-class, potent, and selective investigational oral KRAS G12D dual ON/OFF inhibitor. It is designed to uniquely bind to both the active (ON) and inactive (OFF) states of KRAS G12D, with the potential to inhibit KRAS G12D signaling and tumor growth more completely than compounds that block KRAS G12D only in the OFF state or only in the ON state. In June 2025, Verastem initiated TARGET-D 101, a Phase 1/2 dose escalation, dose expansion, and combination clinical trial evaluating the safety and efficacy of VS-7375 in patients with KRAS G12D-mutated metastatic pancreatic ductal carcinoma (mPDAC), metastatic colorectal cancer (mCRC), advanced non-small cell lung cancer (NSCLC), and other solid tumors. Verastem has further expanded the VS-7375 clinical program with the initiation of three Phase 2 registration-directed, open-label clinical trials: TARGET-D 201 (NCT07644559) in second-line advanced or metastatic PDAC, TARGET-D 202 (NCT07659782) in second/third-line advanced or metastatic NSCLC, and TARGET-D 203 (NCT07659795) in metastatic CRC. In June 2026, the company announced the first patient was dosed in the TARGET-D 201 trial, and in July 2026, the first patient was dosed in the TARGET-D 202 trial. In July 2025, U.S. Food and Drug Administration (FDA) granted Fast Track Designation (FTD) to VS-7375 for the first-line treatment of patients with KRAS G12D-mutated locally advanced or metastatic adenocarcinoma of the pancreas and for the treatment of patients with KRAS G12D-mutated locally advanced or metastatic pancreatic ductal carcinoma who have received at least one prior line of standard systemic therapy. In June 2026, the FDA also granted FTD to VS-7375 for the treatment of adult patients with KRAS G12D-mutated unresectable locally advanced or metastatic non-small cell lung cancer (NSCLC) who have received platinum-based chemotherapy and an anti-PD-(L)1 antibody either concurrently or sequentially. In December 2023, Verastem selected VS-7375 as its lead program from its collaboration with GenFleet Therapeutics, which aims to advance three oncology discovery programs related to RAS/MAPK pathway-driven cancers. The collaboration provides Verastem with an exclusive option to obtain a license for each of the three compounds in the collaboration after the successful completion of pre-determined milestones in a Phase 1 trial. In January 2025, Verastem exercised its license for VS-7375. The licenses would give Verastem development and commercialization rights outside the GenFleet markets of mainland China, Hong Kong, Macau, and Taiwan. GenFleet is developing VS-7375 as GFH375 in China. About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI® FAKZYNJA® CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition. For more information, please visit www.verastem.com and follow us on LinkedIn. Forward-Looking Statements This press release includes forward-looking statements. These forward-looking statements generally can be identified by the use of words such as “anticipate,” “expect,” “plan,” “could,” “may,” “believe,” “estimate,” “forecast,” “goal,” “project,” and other words of similar meaning. Such forward-looking statements address various matters about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans and prospects, including statements related to the potential for and timing of commercialization of product candidates, the anticipated timing for any amendments to the IND application for VS-7375/GFH375, the expected outcome and benefits of the Company’s collaboration with GenFleet Therapeutics (Shanghai), Inc., the timing of commencing and completing trials and compiling data, the expected timing of the presentation of data by the Company and the potential clinical value of various of the Company’s clinical trials. Each forward-looking statement contained in this press release is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such statement. Applicable risks and uncertainties include, among others: the uncertainties inherent in research and development, such as the possibility of negative or unexpected results of clinical trials; that we may not see a return on investment on the payments we have and may continue to make pursuant to the collaboration and option agreement with GenFleet, or that GenFleet may fail to fully perform under the agreement; that we may not be successful in our continued commercialization of AVMAPKI FAKZYNJA CO-PACK; that the development and commercialization of our product candidates may take longer or cost more than planned, including as a result of conducting additional studies or our decisions regarding execution of such commercialization; that data may not be available when expected; risks associated with preliminary and interim data, which may not be representative of more mature data; risks associated with the regulatory and policy actions proposed and enacted by the current U.S. presidential administration that may adversely affect our business; risks associated with the current administration’s reductions to the FDA’s workforce and any subsequent reductions that may lead to disruptions and delays in the FDA’s review and oversight of our product candidates and impact the FDA’s ability to provide timely feedback on our development programs; that our product candidates may not receive regulatory approval, become commercially successful products, or result in new treatment options being offered to patients; and the risks identified under the heading "Risk Factors" as detailed in the Company’s Annual Report on Form 10-K for the year ended December 31, 2025, as filed with the Securities and Exchange Commission (SEC) on March 4, 2026, as well as the other information we file with the SEC, are possibly realized. We caution investors not to place considerable reliance on the forward-looking statements contained in this press release. You are encouraged to read our filings with the SEC, available at www.sec.gov, for a discussion of these and other risks and uncertainties. The forward-looking statements in this press release speak only as of the date of this press release, and we undertake no obligation to update or revise any of these statements. Our business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties. View source version on businesswire.com: https://www.businesswire.com/news/home/20260728067241/en/ For Investor and Media Inquiries: Julissa Viana Senior Vice President, Corporate Communications, Investor Relations & Patient Advocacy investors@verastem.com or media@verastem.com Source: Verastem Oncology