BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced that the Company has completed its rolling New Drug Application (NDA) to the U.S. Food and Drug Administration (FDA) for the investigational and potential first-in-class combination of avutometinib, an oral RAF/MEK clamp, and defactinib, an oral selective FAK inhibitor, for adults with recurrent KRAS mutant low-grade serous ovarian cancer (LGSOC), who received at least one prior systemic therapy..

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（Nasdaq:VSTM）今天宣布，该公司已向美国食品和药物管理局（FDA）完成其滚动新药申请（NDA），用于研究和潜在的一流组合avutometinib（一种口服RAF/MEK钳）和defactinib（一种口服选择性FAK抑制剂），用于复发性KRAS突变型低度浆液性卵巢癌（LGSOC）的成年人，他们至少接受过一次全身治疗。。

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 behavior. Verastem submitted the NDA under the FDA’s Accelerated Approval pathway and requested a Priority Review based on the combination’s potential to address significant unmet medical need among patients with recurrent LGSOC.

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，在生物学和行为上都不同于高度浆液性卵巢癌。Verastem根据FDA的加速批准途径提交了NDA，并要求根据该组合解决复发性LGSOC患者严重未满足医疗需求的潜力进行优先审查。

If granted, the FDA review will be completed within six months following the 60-day filing period. If approved, Verastem expects that avutometinib plus defactinib will be the first-ever FDA-approved treatment specifically for adult patients in the United States with recurrent KRAS mutant LGSOC..

如果获得批准，FDA的审查将在60天申请期后的六个月内完成。如果获得批准，Verastem预计avutometinib加defactinib将是FDA首次批准的专门针对美国复发性KRAS突变LGSOC成年患者的治疗方法。。

“We believe that avutometinib in combination with defactinib has the potential to change the treatment paradigm for patients with recurrent KRAS mutant low-grade serous ovarian cancer,” said Dan Paterson, president and chief executive officer of Verastem Oncology. “Completing our NDA submission is a significant milestone not only for Verastem as we plan for potential FDA approval in mid-2025, but also for patients as there are no FDA-approved treatments specifically for this rare ovarian cancer.”.

Verastem Oncology总裁兼首席执行官丹·帕特森（DanPaterson）表示：“我们认为avutometinib联合defactinib有可能改变复发性KRAS突变型低度浆液性卵巢癌患者的治疗模式。”。“完成我们的NDA提交不仅对Verastem来说是一个重要的里程碑，因为我们计划在2025年年中获得FDA的批准，而且对患者来说也是一个重要的里程碑，因为目前还没有FDA批准的专门针对这种罕见卵巢癌的治疗方法。”。

The Company initiated the rolling NDA submission in May 2024 after reviewing preliminary data with the FDA. Updated results from the Phase 2 registration-directed RAMP 201 study were presented in a late-breaking oral plenary presentation at the International Gynecologic Cancer Society 2024 Annual Meeting and demonstrated in patients with KRAS mutant LGSOC, a confirmed overall response rate (ORR) of 44%, a median progression free survival (PFS) of 22 months, and a disease control rate at 6 months of 70%.

该公司在与FDA审查了初步数据后，于2024年5月开始提交滚动NDA。第二阶段注册指导的RAMP 201研究的最新结果在国际妇科癌症学会2024年年会上的最新口头全体会议上发表，并在KRAS突变LGSOC患者中得到证实，确诊总有效率（ORR）为44%，中位无进展生存期（PFS）为22个月，疾病控制率为6个月为70%。

The updated data continue to demonstrate avutometinib in combination with defactinib is generally well-tolerated, with a 10% discontinuation rate due to adverse events (AEs) across all patients (both KRAS mutant and KRAS wild-type). The NDA submission also includes supportive data from the FRAME Phase 1 trial, the first study conducted with the combination in recurrent LGSOC..

最新数据继续表明，avutometinib联合defactinib通常耐受性良好，由于所有患者（KRAS突变型和KRAS野生型）的不良事件（AE），停药率为10%。NDA提交的资料还包括FRAME第一阶段试验的支持性数据，这是第一项与复发性LGSOC联合进行的研究。。

The FDA previously granted Breakthrough Therapy Designation for avutometinib plus defactinib for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC..

FDA先前批准了avutometinib加defactinib的突破性治疗方案，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。单独使用Avutometinib或与defactinib联合使用也被FDA授予孤儿药名称，用于治疗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 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) is an adaptive, two-part multicenter, parallel cohort, randomized, open-label trial to evaluate the efficacy and safety of avutometinib alone and in combination with defactinib in patients with recurrent low-grade serous ovarian cancer. 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.

RAMP 201（ENGOTov60/GOG3052）是一项适应性，两部分多中心，平行队列，随机，开放标签试验，用于评估avutometinib单独或联合defactinib治疗复发性低度浆液性卵巢癌患者的疗效和安全性。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。

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

该试验的扩展阶段（B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。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 a RAF/MEK clamp that 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RAF/MEK钳，可诱导MEK与ARAF，BRAF和CRAF的无活性复合物，从而通过最大程度的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 other 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，这似乎限制了其他仅MEK抑制剂的功效。。

Verastem Oncology is currently conducting clinical trials with avutometinib 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 (NCT06072781) an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib, a selective FAK inhibitor, versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC).

Verastem Oncology目前正在RAS/MAPK驱动的肿瘤中使用avutometinib进行临床试验，作为其Raf和Mek计划或RAMP的一部分。Verastem目前正在招募RAMP 301（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（一种选择性FAK抑制剂）与标准化疗或激素治疗联合治疗复发性低度浆液性卵巢癌（LGSOC）。

RAMP 201 (NCT04625270) is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and enrollment has been completed for the RAMP 201 trial..

RAMP 201（NCT04625270）是avutometinib联合defactinib治疗复发性LGSOC患者的2期注册指导试验，RAMP 201试验的注册已完成。。

Verastem completed its rolling New Drug Application (NDA) submission 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 in October 2024, with a potential FDA decision mid-2025.

Verastem完成了向美国食品和药物管理局（FDA）提交的滚动新药申请（NDA），用于研究avutometinib和defactinib在2024年10月接受至少一次全身治疗的复发性KRAS突变LGSOC成人中的联合应用，FDA可能在2025年年中做出决定。

The FDA granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib for the treatment of patients with recurrent LGSOC after one or more prior lines of therapy, including platinum-based chemotherapy. Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC..

FDA批准了突破性治疗方案，将avutometinib和defactinib的研究组合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。单独使用Avutometinib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 clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) in combination with avutometinib and defactinib and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant NSCLC as part of the RAMP 203 (NCT05074810) and RAMP 204 (NCT05375994) trials, respectively.

作为RAMP 203（NCT05074810）和RAMP 204（NCT05375994）试验的一部分，Verastem Oncology与Amgen和Mirati建立了临床合作，以评估LUMAKRAS™（sotorasib）联合avutometinib和defactinib以及KRAZATI™（adagrasib）联合avutometinib治疗KRAS G12C突变NSCLC。

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

RAMP 205（NCT05669482）是一项1b/2期临床试验，评估阿维替尼和defactinib与吉西他滨/纳布紫杉醇联合治疗一线转移性胰腺癌患者，得到了PanCAN治疗加速器奖的支持。美国食品和药物管理局（FDA）将孤儿药命名为avutometinib和defactinib联合治疗胰腺癌。。

About Verastem Oncology

关于Verastem Oncology

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。我们的管道专注于RAS/MAPK驱动的癌症，特别是抑制癌症中促进癌细胞存活和肿瘤生长的关键信号传导途径的新型小分子药物，包括RAF/MEK抑制和FAK抑制。