BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with cancer, today announced the initial interim safety and efficacy results from the ongoing RAMP 205 Phase 1/2 clinical trial evaluating avutometinib plus defactinib in combination with gemcitabine and Nab-paclitaxel in the first-line in patients with metastatic pancreatic cancer.

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）今天宣布了正在进行的RAMP 205 1/2期临床试验的初步中期安全性和有效性结果，该试验评估了avutometinib加defactinib联合吉西他滨和Nab紫杉醇治疗转移性胰腺癌患者的一线疗效。

As of May 14, 2024, patients receiving the combination of avutometinib and defactinib with gemcitabine and Nab-paclitaxel in dose level 1 cohort achieved a confirmed overall response rate (ORR) of 83% (5/6), one dose-limiting toxicity (DLT) was observed in the dose level 1 cohort, and the dose level was subsequently cleared after additional patients were enrolled.

截至2024年5月14日，在剂量水平1队列中接受avutometinib和defactinib联合吉西他滨和Nab-紫杉醇治疗的患者的确诊总有效率（ORR）为83%（5/6），在剂量水平1队列中观察到一种剂量限制性毒性（DLT），随后在其他患者入组后清除剂量水平。

The initial interim results will be presented at the upcoming American Society of Clinical Oncology (ASCO) Annual Meeting on June 1, 2024, in a poster session from 1:30-4:30 pm CDT in Chicago, IL.​​.

初步的中期结果将在2024年6月1日即将举行的美国临床肿瘤学会（ASCO）年会上发表，在伊利诺伊州芝加哥CDT下午1:30-4:30的海报会议上。​​.

“The initial interim results from the RAMP 205 trial evaluating avutometinib and defactinib in combination with standard of care first-line chemotherapy are encouraging and demonstrate the importance of targeting the RAS/MAPK pathway, as more than 90% of pancreatic tumors have a KRAS mutation. We continue to progress the study evaluating other dose and schedule regimens to determine the recommended Phase 2 dose in the trial,” said John Hayslip, M.D., chief medical officer of Verastem Oncology.

“RAMP 205试验评估avutometinib和defactinib联合标准治疗一线化疗的初步中期结果令人鼓舞，并证明了靶向RAS/MAPK途径的重要性，因为超过90%的胰腺肿瘤具有KRAS突变。我们继续进行评估其他剂量和时间表方案的研究，以确定试验中推荐的2期剂量，”Verastem Oncology首席医学官约翰·海斯利普医学博士说。

'Metastatic pancreatic cancer continues to be a challenging cancer to treat and these data support the intent behind the Therapeutic Accelerator Award that we received from PanCAN to develop new therapies faster and more efficiently than in historical studies.”.

“转移性胰腺癌仍然是一种具有挑战性的癌症，这些数据支持了我们从PanCAN获得的治疗加速器奖背后的意图，即比历史研究更快更有效地开发新疗法。”。

“Verastem was the inaugural recipient of the PanCAN Therapeutic Accelerator Award, which has been an important part of PanCAN’s approach to advancing innovative treatments for pancreatic cancer,” said Anna Berkenblit, M.D., MMSc, Chief Scientific and Medical Officer at PanCAN. “We look forward to Verastem presenting their initial data from the Phase 1b/2a trial of avutometinib and defactinib in combination with standard care gemcitabine and Nab-paclitaxel in previously untreated metastatic pancreatic cancer at ASCO.

PanCAN首席科学和医学官Anna Berkenblit医学博士说：“Verastem是PanCAN治疗加速器奖的首次获得者，这是PanCAN推进胰腺癌创新治疗方法的重要组成部分。”。“我们期待着Verastem提供他们在ASCO之前未经治疗的转移性胰腺癌中使用avutometinib和defactinib联合标准治疗吉西他滨和Nab-paclitaxel的1b/2a期试验的初步数据。

There is a critical need for new treatment options in this disease, and we hope that the results from this study lead to improved outcomes for patients with pancreatic cancer.”.

这种疾病迫切需要新的治疗选择，我们希望这项研究的结果能够改善胰腺癌患者的预后。”。

Initial Interim Data from RAMP 205 from the Ongoing Phase 1/2 Clinical Trial

来自正在进行的1/2期临床试验的RAMP 205的初始中期数据

As of a data cutoff of May 14, 2024, 41 patients had been treated in one of four dose and schedule cohort regimens of avutometinib and defactinib with gemcitabine and Nab-paclitaxel:

截至2024年5月14日的数据截止日期，41名患者接受了阿维托替尼和defactinib联合吉西他滨和Nab-紫杉醇的四种剂量和时间表队列方案之一的治疗：

In dose level 1, 6 patients received 2.4 mg of avutometinib twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3 weeks out of every 4 and 800 mg/m2 of gemcitabine and 125 mg/m2 of Nab-paclitaxel on a schedule of day 1, day 8 and day 15.

在剂量水平1中，6名患者每周两次（BIW）接受2.4 mg avutometinib，每天两次（BID）200 mg defactinib，持续3周，每4和800 mg/m2吉西他滨和125 mg/m2的Nab紫杉醇，时间表为第1天，第8天和第15天。

In dose level -1, 11 patients received 2.4 mg of avutometinib twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3 weeks out of every 4 with 800 mg/m2 of gemcitabine and 100 mg/m2 of Nab-paclitaxel on a schedule of day 1, day 8 and day 15.

在剂量水平-1中，11名患者每周两次接受2.4 mg avutometinib（BIW），每天两次200 mg defactinib（BID），持续3周，每4次服用800 mg/m2吉西他滨和100 mg/m2的Nab紫杉醇，时间表为第1天，第8天和第15天。

In dose level 1a, 12 patients received 3.2 mg of avutometinib twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3 weeks out of every 4 with 800 mg/m2 of gemcitabine and 125 mg/m2 of Nab-paclitaxel on a schedule of day 1 and day 15.

在剂量水平1a中，12名患者每周两次接受3.2 mg avutometinib（BIW），每天两次200 mg defactinib（BID），持续3周，每4次服用800 mg/m2吉西他滨和125 mg/m2的Nab紫杉醇，时间表为第1天和第15天。

In dose level 2a, 12 patients received 3.2 mg of avutometinib twice a week (BIW), 200 mg of defactinib twice a day (BID) for 3 weeks out of every 4 with 1000 mg/m2 of gemcitabine and 125 mg/m2 of Nab-paclitaxel on a schedule of day 1 and day 15.

在剂量水平2a中，12名患者每周两次接受3.2 mg avutometinib（BIW），每天两次200 mg defactinib（BID），每4次服用1000 mg/m2吉西他滨和125 mg/m2的Nab-紫杉醇，为期3周，第1天和第15天。

As of May 14, 2024, in the dose level 1 cohort, 83% (5/6) of patients achieved a confirmed partial response with more than six months of follow-up at the time of data cutoff. Of the 26 patients in all cohorts who have had the opportunity to have their first scan while on treatment, 21 have experienced a reduction of the change in target lesion sum of diameters..

截至2024年5月14日，在剂量1级队列中，83%（5/6）的患者在数据截止时经过6个月以上的随访，获得了确诊的部分缓解。在所有队列中有26名患者在治疗期间有机会进行第一次扫描，其中21名患者的靶病变总直径变化减少。。

Patients in the trial had a median age of 64 years, 46% were male and 49% had an Eastern Cooperative Oncology Group (ECOG) Performance Status of one.

试验患者的中位年龄为64岁，46%为男性，49%为东部肿瘤协作组（ECOG）的表现状态为1。

Initial Interim Safety Data from All Dose Cohorts

来自所有剂量组群的初始中期安全性数据

As of the May 14, 2024 data cutoff, 12 patients experienced 19 treatment emergent serious adverse events (SAEs), 11 patients with grade ≥3. Grade ≥3 treatment emergent SAEs included blood bilirubin increased (n=2), biliary obstruction (n=2), febrile neutropenia (n=2), pulmonary embolism (n=2), sepsis (n=2), anaemia (n=1), pneumoperitoneum (n=1), septic shock (n=1), skin infection (n=1), malignant neoplasm progression (n=1) and vomiting (n=1).

截至2024年5月14日数据截止，12名患者经历了19次治疗紧急严重不良事件（SAE），11名≥3级患者。≥3级治疗出现的SAE包括血胆红素升高（n=2），胆道梗阻（n=2），发热性中性粒细胞减少（n=2），肺栓塞（n=2），败血症（n=2），贫血（n=1），气腹（n=1），感染性休克（n=1），皮肤感染（n=1），恶性肿瘤进展（n=1）和呕吐（n=1）。

Two patients discontinued treatment due to treatment emergent adverse events (febrile neutropenia, blood bilirubin increased, and detachment of retinal pigment epithelium)..

两名患者因治疗紧急不良事件（发热性中性粒细胞减少症，血胆红素升高和视网膜色素上皮脱离）而停止治疗。。

One dose-limiting toxicity of febrile neutropenia was observed in the dose level 1 cohort and the dose cohort was cleared after additional patients were evaluated. In the additional dose cohorts enrolled more recently (-1, 1a, and 2a), follow up is ongoing and most patients remained on treatment at data cutoff..

在剂量水平1队列中观察到发热性中性粒细胞减少症的一种剂量限制性毒性，并且在评估其他患者后清除了剂量队列。在最近登记的额外剂量队列（-1、1a和2a）中，随访正在进行中，大多数患者在数据截止时仍在接受治疗。。

Conference Call and Webcast Information

电话会议和网络广播信息

Verastem will hold an investor conference call and webcast on Friday, May 24 at 8:00 am EDT, to discuss these data. The call will feature members of Verastem’s management team. To access the conference call, please dial (844) 763-8274 (local) or (412) 717-9224 (international) at least 10 minutes prior to the start time and ask to be joined into the Verastem Oncology conference call.

Verastem将于美国东部时间5月24日（星期五）上午8:00举行投资者电话会议和网络广播，讨论这些数据。这次通话将邀请Verastem管理团队的成员参加。要访问电话会议，请在开始时间前至少10分钟拨打（844）763-8274（本地）或（412）717-9224（国际），并要求加入Verastem肿瘤学电话会议。

A live audio webcast of the call, along with accompany slides, will be accessible here..

您可以在此处访问电话的实时音频网络广播以及伴随的幻灯片。。

About Metastatic Pancreatic Cancer

关于转移性胰腺癌

Pancreatic cancer is the third leading cancer in the U.S. and seventh leading cause of cancer-associated mortality worldwide. Metastatic pancreatic cancer is defined as stage IV cancer, where the cancer spreads to other organs. In the U.S., over 30,000 patients are diagnosed with metastatic pancreatic cancer each year1,2, for which the five-year survival rate is 3%2.

胰腺癌是美国第三大癌症，也是全球癌症相关死亡率的第七大原因。转移性胰腺癌被定义为IV期癌症，癌症扩散到其他器官。在美国，每年有30000多名患者被诊断出患有转移性胰腺癌1,2，其五年生存率为3%2。

Globally, over 240,000 patients are diagnosed with metastatic pancreatic cancer each year3. More than 90% of pancreatic cancers have a KRAS mutation4. The standard of care consists of surgery, chemotherapy, radiation or a combination of these approaches5..

在全球范围内，每年有超过240000名患者被诊断出患有转移性胰腺癌3。超过90%的胰腺癌具有KRAS突变4。护理标准包括手术，化疗，放疗或这些方法的组合5。。

About RAMP 205 Phase 1/2 Study

关于205号坡道1/2期研究

RAMP 205 is a multicenter, open-label, single arm Phase 1b/2a study designed to evaluate the safety, tolerability and efficacy of avutometinib and defactinib in combination with standard of care chemotherapy (gemcitabine and Nab-paclitaxel) in patients with previously untreated metastatic pancreatic ductal adenocarcinoma.

RAMP 205是一项多中心，开放标签，单臂1b/2a期研究，旨在评估avutometinib和defactinib联合标准化疗（吉西他滨和Nab-paclitaxel）对先前未经治疗的转移性胰腺导管腺癌患者的安全性，耐受性和有效性。

Part A of the study will evaluate different dose and schedule combinations to determine the recommended Phase 2 dose for expansion into Part B. RAMP 205 is supported by a PanCAN Therapeutic Accelerator Award..

该研究的A部分将评估不同的剂量和时间表组合，以确定扩展到B部分的推荐2期剂量。RAMP 205得到了PanCAN治疗加速器奖的支持。。

About the Avutometinib and Defactinib Combination

关于Avutometinib和Defactinib的组合

Avutometinib is an investigational RAF/MEK clamp that is designed to induce 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. Avutometinib is designed to block both MEK kinase activity and the ability of RAF to phosphorylate MEK.

Avutometinib是一种研究性RAF/MEK钳，旨在诱导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。Avutometinib旨在阻断MEK激酶活性和RAF磷酸化MEK的能力。

This differentiated proposed mechanism potentially allows avutometinib to block MEK signaling without the compensatory activation of MEK that appears to limit the efficacy of other MEK-only inhibitors. The U.S. Food and Drug Administration (FDA) granted Breakthrough Therapy Designation of the investigational combination of avutometinib and defactinib, a selective FAK inhibitor, for the treatment of all 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.

这种差异化的拟议机制可能允许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。美国食品和药物管理局（FDA）批准了avutometinib和defactinib（一种选择性FAK抑制剂）的研究组合的突破性治疗指定，用于治疗所有复发性低度浆液性卵巢癌（LGSOC）患者，无论一种或多种先前治疗方案（包括铂类化疗）后的KRAS状态如何。

Avutometinib alone or in combination with defactinib was also granted Orphan Drug Designation by the FDA for the treatment of LGSOC..

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 is currently conducting clinical trials with avutometinib in RAS/MAPK driven tumors as part of its Raf And Mek Program or RAMP. RAMP 301 (NCT06072781) is an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent 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。RAMP 301（NCT06072781）是一项国际3期验证性试验，评估avutometinib和defactinib联合治疗与标准化疗或激素治疗复发性LGSOC的疗效。

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 in each of the dose optimization and expansion phases and the low-dose evaluation..

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，已在每个剂量优化和扩展阶段以及低剂量评估中完成注册。。

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..

RAMP 205（NCT05669482）是一项1b/2期临床试验，评估阿维替尼和defactinib联合吉西他滨/纳布紫杉醇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。。

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。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。