BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM) (the “Company”), a biopharmaceutical company committed to advancing new medicines for patients with cancer, announced today the initial safety, pharmacokinetics and recommended Phase 2 dose (RP2D) in the RAMP 203 trial evaluating the safety, tolerability and efficacy of avutometinib in combination with sotorasib in patients with KRAS G12C-mutant non-small cell lung cancer (NSCLC).

BOSTON-（BUSINESS WIRE）-致力于为癌症患者推进新药的生物制药公司Verastem Oncology（纳斯达克股票代码：VSTM）（“公司”）今天宣布初始安全性，药代动力学和推荐阶段2剂量（RP2D）在RAMP 203试验中评估安全性，avutometinib联合sotorasib治疗KRAS G12C突变型非小细胞肺癌（NSCLC）的耐受性和有效性。

The results will be presented at the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics October 11-15, 2023 in Boston, Massachusetts..

结果将于2023年10月11日至15日在马萨诸塞州波士顿举行的AACR-NCI-EORTC分子靶点和癌症治疗国际会议上公布。。

“The RAMP 203 study is investigating the potential benefits of a more complete vertical blockade of the RAS pathway with the combination of avutometinib and sotorasib in KRAS G12C-mutant locally advanced or metastatic NSCLC,” said Mark Awad, M.D., Associate Professor of Medicine at Harvard Medical School and Director of Clinical Research of the Lowe Center for Thoracic Oncology at the Dana-Farber Cancer Institute, investigator on the trial, and presenting author.

“RAMP 203研究正在研究在KRAS G12C突变局部晚期或转移性NSCLC中使用avutometinib和sotorasib联合更完全垂直阻断RAS途径的潜在益处，”Mark Awad，M.D。说。，哈佛医学院医学副教授，Dana-Farber癌症研究所Lowe胸部肿瘤中心临床研究主任，试验研究员和提交作者。

“These initial findings, including the recommended Phase 2 dose and the encouraging preliminary efficacy and safety results, provide support for the combination, and I look forward to completing the expansion phase of the trial.”.

“这些初步结果，包括推荐的2期剂量和令人鼓舞的初步疗效和安全性结果，为组合提供了支持，我期待完成试验的扩展阶段。”。

RAMP 203 (NCT05074810) is a Phase 1/2, multicenter, open label, dose evaluation/expansion study evaluating the efficacy and safety of avutometinib + sotorasib in patients with KRAS G12C-mutant NSCLC who have not been previously treated with a KRAS G12C inhibitor as well as in patients who have been previously treated with a KRAS G12C inhibitor.

RAMP 203（NCT05074810）是一项1/2期多中心，开放标签，剂量评估/扩展研究，评估avutometinib+sotorasib对KRAS G12C突变NSCLC患者的疗效和安全性，这些患者之前未接受过KRAS G12C治疗抑制剂以及之前接受过KRAS G12C抑制剂治疗的患者。

The confirmed objective response rate (ORR) was 25% (3/12) across efficacy-evaluable patients and seen in both KRAS G12C inhibitor resistant (14.3%; 1/7) and naïve (40%; 2/5) patients..

KRAS G12C抑制剂耐药（14.3%；1/7）和初治（40%；2/5）患者的确诊客观缓解率（ORR）为25%（3/12）。。

The pharmacokinetic profile of avutometinib in combination with sotorasib was similar to results in monotherapy studies. No drug-drug interactions were observed between avutometinib and sotorasib. Avutometinib 4.0 mg PO BIW 21/28 days + sotorasib 960 mg PO QD 28/28 days was selected as RP2D based on dose limiting toxicity (DLT) assessment.

avutometinib联合sotorasib的药代动力学特征与单药治疗研究的结果相似。avutometinib和sotorasib之间未观察到药物相互作用。基于剂量限制性毒性（DLT）评估，选择Avutometinib 4.0mg PO BIW 21/28天+sotorasib 960mg PO QD 28/28天作为RP2D。

Enrollment of patients with KRAS G12C-mutant NSCLC who are either naïve to or previously treated with a KRAS G12C inhibitor is ongoing in the expansion phase of RAMP 203..

在RAMP 203的扩展阶段，正在招募KRAS G12C突变NSCLC患者，这些患者既可以接受KRAS G12C抑制剂治疗，也可以接受KRAS G12C抑制剂治疗。。

“The RAMP 203 trial builds on preclinical data which demonstrated the addition of avutometinib to sotorasib improved the depth of MAPK pathway inhibition and substantially enhanced tumor regression relative to sotorasib alone,” said Dan Paterson, President and CEO, Verastem Oncology. “Given KRAS G12C mutations are the most common KRAS mutation in NSCLC and acquired mutations and amplifications occur upon clinical progression to KRAS G12C inhibitor monotherapy, the results of the RAMP 203 trial are important in understanding potential new treatment approaches for patients.”.

Verastem肿瘤学总裁兼首席执行官Dan Paterson说：“RAMP 203试验建立在临床前数据的基础上，证明了avutometinib在sotorasib中的加入改善了MAPK通路抑制的深度，并显着增强了肿瘤消退。“鉴于KRAS G12C突变是NSCLC中最常见的KRAS突变，并且在临床进展为KRAS G12C抑制剂单一疗法时发生获得性突变和扩增，RAMP 203试验的结果对于理解患者潜在的新治疗方法非常重要。”。

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 increased RAS pathway inhibition. In contrast to currently available MEK inhibitors, avutometinib blocks both MEK kinase activity and the ability of RAF to phosphorylate MEK.

Avutometinib是一种RAF/MEK钳夹，可诱导MEK与ARAF，BRAF和CRAF的失活复合物，可能通过增加RAS途径抑制作用而产生更完整，更持久的抗肿瘤反应。与目前可用的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 inhibitors. The U.S. Food and Drug Administration granted Breakthrough Therapy designation for the combination of Verastem Oncology’s investigational RAF/MEK clamp avutometinib, with defactinib, its FAK inhibitor, for the treatment of patients with recurrent low-grade serous ovarian cancer (LGSOC) regardless of KRAS status after one or more prior lines of therapy, including platinum-based chemotherapy..

这种独特的机制允许avutometinib阻断MEK信号传导而没有MEK的代偿性激活，这似乎限制了其他抑制剂的功效。美国食品和药物管理局授予突破性疗法名称，将Verastem肿瘤学研究RAF/MEK钳夹avutometinib与defactinib（其FAK抑制剂）联合用于治疗复发性低度浆液性卵巢癌（LGSOC）患者，无论KRAS状态如何在一个或多个先前的治疗线之后，包括铂基化疗。。

Verastem Oncology is currently conducting clinical trials with its RAF/MEK clamp avutometinib in RAS pathway-driven tumors as part of its Raf And Mek Program (RAMP). RAMP 301 is a Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent LGSOC.

作为RAF和MEK计划（RAMP）的一部分，Verastem Oncology目前正在RAF/MEK钳夹avutometinib在RAS途径驱动的肿瘤中进行临床试验。RAMP 301是一项3期验证性试验，评估avutometinib和defactinib联合标准化疗或激素治疗复发性LGSOC的疗效。

RAMP 201 is a Phase 2 registration-directed trial of avutometinib in combination with defactinib in patients with recurrent LGSOC and has completed enrollment in the dose optimization and expansion phases and is enrolling for low-dose evaluation. Verastem Oncology has established clinical collaborations with Amgen and Mirati to evaluate LUMAKRAS™ (sotorasib) and KRAZATI™ (adagrasib) in combination with avutometinib in KRAS G12C mutant-NSCLC as part of the RAMP 203 and RAMP 204 trials, respectively.

RAMP 201是avutometinib联合defactinib治疗复发性LGSOC患者的2期注册指导试验，已完成剂量优化和扩展阶段的注册，并正在进行低剂量评估。Verastem肿瘤学与Amgen和Mirati建立了临床合作关系，以评估LUMAKRAS™ （sotorasib）和KRAZATI™ （adagrasib）联合avutometinib治疗KRAS G12C突变NSCLC，分别作为RAMP 203和RAMP 204试验的一部分。

Supported by the “Therapeutic Accelerator Award” Verastem Oncology received from PanCAN, the Company is conducting RAMP 205, a Phase 1b/2 clinical trial evaluating avutometinib and defactinib with gemcitabine/nab-paclitaxel in patients with front-line metastatic pancreatic cancer..

在PanCAN收到的“治疗加速器奖”Verastem Oncology的支持下，该公司正在进行RAMP 205，这是一项1b/2期临床试验，评估avutometinib和defactinib联合吉西他滨/纳他紫杉醇治疗一线转移性胰腺癌患者。。

About Verastem Oncology

关于Verastem肿瘤学

Verastem Oncology (Nasdaq: VSTM) is a development-stage 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 novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition and focal adhesion kinase (FAK) inhibition.

Verastem Oncology（纳斯达克股票代码：VSTM）是一家开发阶段的生物制药公司，致力于新药的开发和商业化，以改善诊断为癌症的患者的生活。我们的研究重点是新型小分子药物，这些药物可抑制癌症中促进癌细胞存活和肿瘤生长的关键信号通路，包括RAF/MEK抑制和粘着斑激酶（FAK）抑制。

For more information, please visit www.verastem.com..

欲了解更多信息，请访问www.verastem.com。。

Forward-Looking Statements Notice

前瞻性声明通知

This press release includes forward-looking statements about Verastem Oncology’s strategy, future plans and prospects, including statements related to the potential clinical value of various of its clinical trials. 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.

本新闻稿包括关于Verastem Oncology战略，未来计划和前景的前瞻性声明，包括与其各种临床试验的潜在临床价值相关的声明。“预期”，“相信”，“估计”，“期望”，“打算”，“可能”，“计划”，“预测”，“项目”，“目标”，“潜力”，“将会”，“将会”，“应该，“，”应该“，”继续“，”可以“，”有希望“和类似的表达方式是为了识别前瞻性陈述，尽管不是所有的前瞻性陈述都包含这些标识词。

Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement..

每个前瞻性声明都存在风险和不确定性，可能导致实际结果与本声明中表达或暗示的结果大不相同。。

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, LUMAKRASTM and others; the occurrence of adverse safety events and/or unexpected concerns that may arise from additional data or analysis or result in unmanageable safety profiles as compared to their levels of efficacy; 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 will be predictive of the results or success of ongoing or later clinical trials; that the timing, scope and rate of reimbursement for our product candidates is uncertain; that third-party payors (including government agencies) may not reimburse; that there may be competitive developments affecting our product candidates; that we may not attract and retain high quality personnel; that data may not be available when expected; that enrollment of clinical trials may take longer than expected; that our product candidates will experience manufacturing or supply interruptions or failures; that we will be unable to successfully initiate or complete the clinical development and eventual commercialization of our product candidates; that the development and commercialization of our product candidates will take longer or cost more than .

适用的风险和不确定性包括风险和不确定性，其中包括：我们的候选产品（包括avutometinib联合其他化合物，包括defactinib，LUMAKRASTM等）的开发和潜在商业化的成功；与其有效性水平相比，可能由额外数据或分析引起的不良安全事件和/或意外问题的发生或导致难以管理的安全性概况；我们为产品候选人获得，维护和执行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；监管机构就可能影响我们产品候选人的时间，可用性或商业潜力的试验设计，标签和其他事项做出决定；我们的候选产品的临床前测试和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；我们的产品候选人的报销时间，范围和费率尚不确定；第三方付款人（包括政府机构）不得报销；可能有竞争发展影响我们的产品候选人；我们可能不会吸引和留住高质量的人员；预期时可能无法获得该数据；临床试验的入学时间可能比预期的要长；我们的候选产品将经历制造或供应中断或故障；我们将无法成功启动或完成我们候选产品的临床开发和最终商业化；我们候选产品的开发和商业化将花费更长的时间或成本。

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, 2022 as filed with the Securities and Exchange Commission (SEC) on March 14, 2023 and in any subsequent filings with the SEC. The forward-looking statements contained in this press release reflect Verastem Oncology’s views as of the date hereof, and Verastem Oncology 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..

其他风险和不确定性包括2023年3月14日提交给美国证券交易委员会（SEC）的本公司年度报告中截至2022年12月31日的表格10-K中“风险因素”标题下确定的风险和不确定性。以及随后向SEC提交的任何文件。本新闻稿中包含的前瞻性声明反映了Verastem Oncology截至本协议签署之日的观点，Verastem Oncology不承担并明确拒绝任何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，除非法律要求。。