BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced that the U.S. Food and Drug Administration (FDA) has accepted for review the New Drug Application (NDA) under the accelerated approval pathway for avutometinib, an oral RAF/MEK clamp, in combination with defactinib, an oral FAK inhibitor, for the treatment of adult patients with recurrent low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy and have a KRAS mutation.

波士顿--（商业新闻短讯）--致力于为癌症患者开发新药的生物制药公司Verastem Oncology（纳斯达克：VSTM）今天宣布，美国食品和药物管理局（FDA）已接受根据口服RAF/MEK钳avutometinib与口服FAK抑制剂defactinib联合加速批准途径审查新药申请（NDA），用于治疗复发性低度浆液性卵巢癌（LGSOC）的成年患者，这些患者至少接受过一次全身治疗并且有KRAS突变。

The NDA, which was completed in October 2024, has been granted Priority Review with a Prescription Drug User Fee Act (PDUFA) action date of June 30, 2025. In addition, the FDA has stated that it is not currently planning to hold an advisory committee meeting to discuss the application..

该保密协议于2024年10月完成，并于2025年6月30日通过了《处方药用户费用法案》（PDUFA）的优先审查。此外，FDA表示，目前不打算召开咨询委员会会议讨论该申请。。

“The FDA filing acceptance and Priority Review for the combination of avutometinib and defactinib underscores the critical unmet need among patients diagnosed with this rare and insidious disease. We are excited by today’s news and to potentially bring the first ever FDA-approved treatment specifically for recurrent KRAS mutant LGSOC to patients in the U.S.,” said Dan Paterson, president and chief executive officer of Verastem Oncology.

Verastem Oncology总裁兼首席执行官丹·帕特森（DanPaterson）表示：“FDA对avutometinib和defactinib联合用药的申请受理和优先审查强调了被诊断患有这种罕见和隐匿性疾病的患者的关键需求尚未得到满足。我们对今天的消息感到兴奋，并有可能为美国患者带来首次FDA批准的针对复发性KRAS突变LGSOC的治疗。”。

“With the acceptance of this NDA, we’re taking an important step forward in addressing a condition that has long been overlooked, and we look forward to working with the FDA during its review process and preparing for a commercial launch in mid-2025.”.

“随着这份保密协议的接受，我们在解决长期以来被忽视的问题方面迈出了重要的一步，我们期待着在审查过程中与FDA合作，并为2025年年中的商业启动做好准备。”。

There are currently no FDA-approved treatments specifically for LGSOC, a rare and distinct ovarian cancer that differs from high-grade serous ovarian cancer in both its biology and how it responds to treatment. Priority Review is granted by the FDA for treatments that offer, if approved, significant improvements over available options or that provide a treatment option where no adequate or approved therapy currently exists..

目前还没有FDA批准的专门针对LGSOC的治疗方法，LGSOC是一种罕见且独特的卵巢癌，在生物学和治疗反应方面都不同于高度浆液性卵巢癌。美国食品和药物管理局（FDA）授予优先审查的治疗方法是，如果获得批准，可以显着改善现有的选择，或者在目前没有足够或批准的治疗方法的情况下提供治疗选择。。

The filing was based on a primary analysis of the Phase 2 RAMP 201 clinical trial that evaluated the combination of avutometinib and defactinib in patients with recurrent LGSOC. The results were presented in an oral presentation at the International Gynecologic Cancer Society (IGCS) Annual Global Meeting in October 2024 and demonstrated that the combination of avutometinib plus defactinib resulted in a substantial overall response rate confirmed by blinded independent central review, with responses that were typically durable, and that the combination was generally well-tolerated in patients with recurrent KRAS mutant LGSOC.

该申请是基于对2期RAMP 201临床试验的初步分析，该试验评估了avutometinib和defactinib联合治疗复发性LGSOC患者。研究结果在2024年10月举行的国际妇科癌症协会（IGCS）年度全球会议上发表了口头报告，并证明avutometinib加defactinib的联合治疗可产生显着的总体缓解率，这一结果已通过盲法独立中央评估得到证实，其反应通常是持久的，并且该组合在复发性KRAS突变LGSOC患者中通常具有良好的耐受性。

The NDA also includes supportive data from the FRAME Phase 1 trial, the first study conducted with the combination therapy in recurrent LGSOC..

。。

The Company is currently enrolling patients with recurrent LGSOC regardless of KRAS mutation status for RAMP 301, an international Phase 3 trial, which will serve as a confirmatory study for the initial indication and has the potential to support an expanded indication regardless of KRAS mutation status..

该公司目前正在招募复发性LGSOC患者，无论RAMP 301的KRAS突变状态如何，这是一项国际3期试验，将作为初始适应症的验证性研究，并有可能支持扩大适应症，无论KRAS突变状态如何。。

About RAMP 201

关于匝道201

RAMP 201 (ENGOTov60/GOG3052) (NCT04625270) is an adaptive, two-part multicenter, parallel cohort, randomized, open-label Phase 2 registration-directed trial evaluating the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer (LGSOC).

RAMP 201（ENGOTov60/GOG3052）（NCT04625270）是一项适应性，两部分多中心，平行队列，随机，开放标签的2期注册指导试验，评估单独使用avutometinib和联合使用defactinib治疗复发性低度浆液性卵巢癌（LGSOC）患者的疗效和安全性。

The first part of the study (Part A) determined the selection of the go-forward regimen, which was the combination of avutometinib and defactinib versus avutometinib alone, based on overall response rates. The expansion phases of the trial (Parts B and C) are evaluating the safety and efficacy of the go-forward regimen of avutometinib 3.2 mg twice weekly and defactinib 200 mg twice daily.

研究的第一部分（A部分）根据总体缓解率确定了前进方案的选择，该方案是avutometinib和defactinib与单独avutometinib的组合。试验的扩展阶段（B部分和C部分）正在评估avutometinib 3.2 mg每周两次和defactinib 200 mg每日两次的前进方案的安全性和有效性。

The Part D portion of the trial is evaluating a low dose of avutometinib in combination with defactinib to inform individualized dose reduction..

试验的D部分正在评估低剂量的avutometinib联合defactinib，以告知个体化剂量减少。。

About Low-Grade Serous Ovarian Cancer (LGSOC)

关于低度浆液性卵巢癌（LGSOC）

LGSOC is a rare ovarian cancer that is insidious, persistent, and ultimately fatal. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S.

LGSOC是一种罕见的卵巢癌，具有隐匿性，持续性和最终致命性。LGSOC与高度浆液性卵巢癌（HGSOC）不同，需要不同的治疗。与HGSOC相比，LGSOC高度复发，对化疗的敏感性较低。美国大约有6000-8000名女性。

and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life.

全世界有80000人患有这种疾病。LGSOC影响年龄在20-30至50-60岁之间的双峰诊断的年轻女性，中位生存期约为十年。大多数患者报告LGSOC对他们的身心健康，生育能力和长期生活质量产生负面影响。

The current standard of care for this disease includes hormone therapy and chemotherapy, but there are no treatments specifically approved by the U.S. Food and Drug Administration to treat LGSOC..

目前治疗这种疾病的标准包括激素治疗和化疗，但美国食品和药物管理局没有专门批准用于治疗LGSOC的治疗方法。。

About the Avutometinib and Defactinib ​​Combination

关于Avutometinib和Defactinib的组合

Avutometinib is an oral RAF/MEK clamp that potentially inhibits MEK1/2 kinase activities and induces inactive complexes of MEK with ARAF, BRAF, and CRAF, potentially creating a more complete and durable anti-tumor response through maximal RAS/MAPK pathway inhibition. In contrast to currently available MEK-only inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK.

Avutometinib是一种口服RAF/MEK钳，可能抑制MEK1/2激酶活性，并诱导MEK与ARAF，BRAF和CRAF的无活性复合物，可能通过最大的RAS/MAPK途径抑制产生更完整和持久的抗肿瘤反应。与目前可用的仅MEK抑制剂相反，avutometinib阻断MEK激酶活性和RAF磷酸化MEK的能力。

This unique mechanism allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of the MEK-only inhibitors..

这种独特的机制允许avutometinib阻断MEK信号传导，而不需要MEK的补偿性激活，这似乎限制了仅MEK抑制剂的功效。。

Defactinib is an oral, selective inhibitor of focal adhesion kinase (FAK) and proline-rich tyrosine kinase-2 (Pyk2), the two members of the focal adhesion kinase family of non-receptor protein tyrosine kinases. FAK and Pyk2 integrate signals from integrin and growth factor receptors to regulate cell proliferation, survival, migration, and invasion.

Defactinib是粘着斑激酶（FAK）和富含脯氨酸的酪氨酸激酶-2（Pyk2）的口服选择性抑制剂，这是非受体蛋白酪氨酸激酶粘着斑激酶家族的两个成员。FAK和Pyk2整合整合素和生长因子受体的信号，以调节细胞增殖，存活，迁移和侵袭。

FAK activation has been shown to mediate resistance to multiple anti-cancer agents, including RAF and MEK inhibitors..

FAK激活已被证明可介导对多种抗癌药物的耐药性，包括RAF和MEK抑制剂。。

Verastem Oncology is currently conducting clinical trials with avutometinib with and without defactinib in RAS/MAPK-driven tumors as part of its Raf And Mek Program or RAMP. Verastem is currently enrolling patients and activating sites for RAMP 301 (GOG-3097/ENGOT-ov81/NCRI) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC)..

作为其Raf和Mek计划或RAMP的一部分，Verastem Oncology目前正在RAS/MAPK驱动的肿瘤中进行avutometinib联合或不联合defactinib的临床试验。Verastem目前正在招募RAMP 301（GOG-3097/ENGOT-ov81/NCRI）（NCT06072781）的患者和激活位点，这是一项国际3期验证性试验，评估avutometinib和defactinib联合治疗复发性低度浆液性卵巢癌（LGSOC）的标准化疗或激素治疗。。

Verastem was granted Priority Review and a Prescription Drug User Fee Act (PDUFA) date of June 30, 2025, for its New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA), for the investigational combination of avutometinib and defactinib in adults with recurrent KRAS mutant LGSOC who received at least one prior systemic therapy.

Verastem于2025年6月30日向美国食品和药物管理局（FDA）提交了新药申请（NDA），并于2025年6月30日获得了优先审查和处方药使用费法案（PDUFA），用于研究avutometinib和defactinib在复发性KRAS突变LGSOC患者中的联合应用，这些患者至少接受过一次全身治疗。

Verastem initiated a rolling NDA in May 2024 to the FDA and completed its NDA submission in October 2024. The FDA granted Breakthrough Therapy Designation for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy, in May 2021. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC..

Verastem于2024年5月向FDA提交了滚动保密协议，并于2024年10月完成了保密协议的提交。2021年5月，FDA批准了突破性治疗方案，用于治疗一种或多种先前治疗方案（包括铂类化疗）后复发性LGSOC患者。Avutometinib单独或与defactinib联合使用也被FDA授予孤儿药名称，用于治疗LGSOC。。

Verastem Oncology has established a clinical collaboration with Amgen to evaluate LUMAKRAS™ (sotorasib) in combination with avutometinib and defactinib in both treatment-naïve patients and in patients whose KRAS G12C mutant non-small cell lung cancer progressed on a G12C inhibitor as part of the RAMP 203 trial (NCT05074810).

Verastem Oncology与Amgen建立了临床合作，以评估LUMAKRAS™（sotorasib）联合avutometinib和defactinib治疗初治患者以及KRAS G12C突变非小细胞肺癌在G12C抑制剂上进展的患者作为RAMP 203试验的一部分（NCT05074810）。

Verastem has received Fast Track Designation from the FDA for the triplet combination in April 2024. RAMP 205 (NCT05669482), a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer, is supported by the PanCAN Therapeutic Accelerator Award.

Verastem于2024年4月获得了FDA关于三联组合的快速通道指定。。

FDA granted Orphan Drug Designation to the avutometinib and defactinib combination for the treatment of pancreatic cancer..

美国食品和药物管理局（FDA）将孤儿药指定为用于治疗胰腺癌的avutometinib和defactinib组合。。

About Verastem Oncology

关于真性肿瘤学

Verastem Oncology (Nasdaq: VSTM) is a late-stage development biopharmaceutical company committed to the development and commercialization of new medicines to improve the lives of patients diagnosed with cancer. Our pipeline is focused on RAS/MAPK-driven cancers, specifically novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and FAK inhibition.

Verastem Oncology（纳斯达克：VSTM）是一家晚期开发生物制药公司，致力于新药的开发和商业化，以改善被诊断患有癌症的患者的生活。。

For more information, please visit www.verastem.com and follow us on LinkedIn..

欲了解更多信息，请访问www.verastem.com并在LinkedIn上关注我们。。

Forward-Looking Statements

前瞻性声明

This press release includes forward-looking statements about, among other things, Verastem Oncology’s programs and product candidates, strategy, future plans, and prospects, including statements related to the expected timing of the FDA action on the New Drug Application (NDA) for the avutometinib and defactinib combination product in KRAS-mutant and recurrent low-grade serous ovarian cancer, the potential clinical value of various of the Company’s clinical trials, including the RAMP 201, RAMP 203, RAMP 205 and RAMP 301 trials, the timing of commencing and completing trials and compiling data, including topline data and reports, interactions with regulators, the potential for and timing of commercialization of product candidates and potential for additional development programs involving Verastem Oncology’s lead compound.

本新闻稿包括关于Verastem Oncology的计划和候选产品、战略、未来计划和前景的前瞻性声明，其中包括与FDA对KRAS突变型和复发性低度浆液性卵巢癌新药申请（NDA）采取行动的预期时间有关的声明，包括与FDA对新药申请（NDA）采取行动的预期时间，公司各种临床试验（包括RAMP 201、RAMP 203、RAMP 205和RAMP 301试验）的潜在临床价值，开始和完成试验的时间以及汇编数据的时间，包括topline数据和报告，与监管机构的互动，候选产品商业化的潜力和时间，以及涉及维拉帕米的其他开发计划的潜力STEM肿瘤学的先导化合物。

The words 'anticipate,' 'believe,' 'estimate,' 'expect,' 'intend,' 'may,' 'plan,' 'predict,' 'project,' 'target,' 'potential,' 'will,' 'would,' 'could,' 'should,' 'continue,' “can,” “promising” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words..

“预期”，“相信”，“估计”，“期望”，“打算”，“可能”，“计划”，“预测”，“项目”，“目标”，“潜力”，“意志”，“会”，“可能”，“应该”，“继续”，“可以”，“有希望”和类似的表达都是为了识别前瞻性陈述，尽管并非所有的前瞻性陈述都包含这些识别词。。

Forward-looking statements are not guarantees of future performance and are subject to risks and uncertainties that could cause our actual results to differ materially from those expressed or implied in the forward-looking statements we make. Applicable risks and uncertainties include the risks and uncertainties, among other things, regarding: the success in the development and potential commercialization of our product candidates, including avutometinib in combination with other compounds, including defactinib, LUMAKRAS™ and others; the uncertainties inherent in research and development, such as negative or unexpected results of clinical trials, the occurrence or timing of applications for our product candidates that may be filed with regulatory authorities in any jurisdictions; whether and when regulatory authorities in any jurisdictions may approve or reject any such applications that may be filed for our product candidates, and, if approved, whether our product candidates will be commercially successful in such jurisdictions; our ability to obtain, maintain and enforce patent and other intellectual property protection for our product candidates; the scope, timing, and outcome of any legal proceedings; decisions by regulatory authorities regarding trial design, labeling and other matters that could affect the timing, availability or commercial potential of our product candidates; whether preclinical testing of our product candidates and preliminary or interim data from clinical trials is predictive of the results or success of ongoing or later clinical trials; the uncertainty around the timing, scope and rate of reimbursement for our product candidates; internal and third-party estimates about the market opportunities of our drug candidates may prove to be incorrect;.

前瞻性陈述并不能保证未来的业绩，并且存在风险和不确定性，这些风险和不确定性可能导致我们的实际结果与我们所做的前瞻性陈述中明示或暗示的结果产生重大差异。适用的风险和不确定性包括以下方面的风险和不确定性：我们的候选产品（包括avutometinib与其他化合物（包括defactinib，LUMAKRAS™等）的开发成功和潜在商业化；研究和开发中固有的不确定性，例如临床试验的负面或意外结果，可能向任何司法管辖区的监管机构提交的候选产品申请的发生或时间；任何司法管辖区的监管机构是否以及何时可以批准或拒绝为我们的候选产品提交的任何此类申请，如果获得批准，我们的候选产品是否会在这些司法管辖区取得商业成功；我们为候选产品获得、维护和实施专利和其他知识产权保护的能力；任何法律诉讼的范围、时间和结果；监管机构关于试验设计、标签和其他可能影响我们候选产品的时间、可用性或商业潜力的事项的决定；我们的候选产品的临床前测试以及临床试验的初步或中期数据是否可以预测正在进行或以后的临床试验的结果或成功；我们的候选产品的偿还时间、范围和费率存在不确定性；；。

Other risks and uncertainties include those identified under the heading “Risk Factors” in the Company’s Annual Report on Form 10-K for the year ended December 31, 2023, as filed with the Securities and Exchange Commission (SEC) on March 14, 2024, and in any subsequent filings with the SEC, which are available at www.sec.gov.

其他风险和不确定性包括2024年3月14日提交给美国证券交易委员会（SEC）的公司截至2023年12月31日的年度报告中“风险因素”标题下确定的风险和不确定性，以及随后提交给SEC的任何文件中确定的风险和不确定性，这些文件可在www.SEC.gov上查阅。

The forward-looking statements contained in this press release reflect Verastem Oncology’s views as of the date hereof, and the Company does not assume and specifically disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by law..

本新闻稿中包含的前瞻性声明反映了Verastem Oncology截至本新闻稿发布之日的观点，除法律要求外，公司不承担并明确否认更新任何前瞻性声明的义务，无论是由于新信息、未来事件还是其他原因。。