After a major phase 2 win that stirred up much excitement within the oncology community, Merck & Co. has officially formulated a pivotal trial plan for its Moderna-partnered personalized cancer vaccine, mRNA-4157.

在肿瘤学界引起广泛兴奋的第二阶段胜利之后，默克公司正式制定了其Moderna合作的个性化癌症疫苗mRNA-4157的关键试验计划。

A phase 3 trial coded V940-001 will test the combination of the mRNA vaccine, also known as V940, and Merck’s PD-1 inhibitor Keytruda for post-surgery treatment of patients with resected melanoma that’s at high risk of recurrence. The trial was posted on ClinicalTrials.gov Thursday and is expected to kick off Aug.

编码V940-001的3期试验将测试mRNA疫苗（也称为V940）和Merck的PD-1抑制剂Keytruda的组合，用于手术后治疗复发风险高的切除黑素瘤患者。该试验于周四在ClinicalTrials.gov上发布，预计将于8月启动。

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The vaccine is made by profiling each patient’s tumor mutational signature and is designed to induce an immune response against the corresponding antigens. If eventually successful, Merck and Moderna could open up an entirely new area of cancer treatment.

通过分析每个患者的肿瘤突变特征来制备疫苗，并设计用于诱导针对相应抗原的免疫应答。如果最终成功，默克和Moderna可以开辟一个全新的癌症治疗领域。

Merck pushed V940 into phase 3 after the phase 2b KEYNOTE-942 study showed that the vaccine’s combination with Keytruda reduced the risk of recurrence or death by 44% compared with Keytruda alone for the adjuvant, or post-surgery, treatment of resectable melanoma.

在2b期KEYNOTE-942研究显示疫苗与Keytruda联合使用可复发或死亡的风险比单独使用Keytruda的佐剂或手术后治疗可切除的黑色素瘤降低44%后，默克公司将V940推向第3阶段。

Both studies use Keytruda monotherapy as the comparator and use recurrence-free survival as the primary endpoint. But the phase 3 trial is different from its predecessor in several ways.

两项研究均使用Keytruda单药治疗作为比较，并使用无复发生存率作为主要终点。但第三阶段试验在几个方面与其前身不同。

First, while the midstage trial data included patients with stage 3b to 4 melanoma, the new phase 3 stretches to disease as early as stage 2b.

首先，虽然中期试验数据包括3b至4期黑色素瘤患者，但新的3期早在2b期就延伸至疾病。

The wider patient population didn’t come as a surprise, Leerink Partners analyst Daina Graybosch, Ph.D., said in an email with Fierce Biotech. Keytruda monotherapy is currently approved as an adjuvant treatment for stage 2b to 3 melanoma following complete resection, and Merck has said it plans to cover the entire spectrum where Keytruda is approved, she noted..

Leerink Partners分析师Daina Graybosch博士在一封带有激烈生物技术的电子邮件中说，更广泛的患者人群并不意外。她指出，Keytruda单药治疗目前被批准作为完全切除后2b至3期黑色素瘤的辅助治疗，默克表示，它计划覆盖Keytruda获得批准的整个范围。。

V940-001 is expected to enroll 1,089 patients, making it much larger than the 157-patient phase 2b study. The ongoing midstage trial started mid-2019 and read out positively toward the end of 2022. By comparison, V940-001 bears a primary completion date six years from now in October 2029. It’s not clear what plan Merck has for any interim analyses.

V940-001预计将招募1089名患者，这比157名患者的2b期研究大得多。正在进行的中期试验开始于2019年中期，并在2022年底积极读出。相比之下，V940-001的主要完成日期为2029年10月的六年。目前还不清楚默克公司对任何中期分析有什么计划。

A spokesperson said the company will share more information once the trial has been initiated..

一位发言人表示，一旦审判开始，公司将分享更多信息。。

If we look for past experience, Bristol Myers Squibb previously found that adding its CTLA-4 agent Yervoy to the adjuvant Opdivo didn’t improve recurrence-free survival in stage 3b to 4 melanoma. The company announced the failure of CheckMate-915 in October 2020, three and a half years into the study..

如果我们寻找过去的经验，Bristol-Myers Squibb先前发现将其CTLA-4药物Yervoy添加到佐剂Opdivo中并不能改善3b至4期黑素瘤的无复发生存期。该公司于2020年10月宣布CheckMate-915失败，即研究三年半。。

PD-1 inhibitors are the current standard of care in adjuvant melanoma, so Keytruda is the appropriate comparator for V940-001. But by the time the trial reads out, a new standard of care could have emerged, Graybosch noted.

PD-1抑制剂是佐剂性黑素瘤的当前护理标准，因此Keytruda是V940-001的合适比较物。但Graybosch指出，在试验结束时，可能会出现一种新的护理标准。

BMS is nearly two years into the RELATIVITY-098 trial for its PD-1/LAG-3 combo Opdualag in stage 3 to 4 melanoma, with primary completion data estimated for February 2026. Merck itself recently launched another phase 3 trial dubbed KEYVIBE-010, which is pairing Keytruda with the TIGIT inhibitor vibostolimab..

BMS在第3至4期黑色素瘤的PD-1/LAG-3组合Opdualag的REVISION-098试验已经进行了近两年，主要完成数据估计为2026年2月。默克公司最近推出了另一项名为KEYVIBE-010的3期临床试验，该试验将Keytruda与TIGIT抑制剂vibostolimab配对。。

Compared with the new cancer vaccine study, that TIGIT trial is larger with a planned 1,560 participants and has an earlier primary completion date in October 2027. Both trials are in stage 2 to 4 melanoma.

与新的癌症疫苗研究相比，TIGIT试验规模更大，计划有1560名参与者，并于2027年10月提前完成。两项试验均处于2至4期黑色素瘤。

The smaller trial size for V940-001 could reflect Merck’s confidence in the cancer vaccine’s efficacy given the strong phase 2b results. But the longer trial timeline could mean that the company expects more follow-up time to see a clear efficacy signal for the vaccine.

鉴于强大的2b期结果，V940-001较小的试验规模可能反映了默克对癌症疫苗疗效的信心。但较长的试验时间表可能意味着该公司预计会有更多的随访时间来观察疫苗的明确疗效信号。

Cancer vaccines have seen many failures in the past, and the encouraging phase 2b KEYNOTE-942 results gave people hope that the personalized mRNA vaccine might end the category’s troubled history.

癌症疫苗过去曾出现过许多失败，令人鼓舞的2b期KEYNOTE-942结果使人们希望个性化mRNA疫苗可能结束该类别的困扰历史。

Graybosch expects that any statistically significant data from V940-001 could change practice, “especially as the vaccine is so tolerable.”

Graybosch预计，来自V940-001的任何具有统计意义的数据都可能改变实践，“特别是因为疫苗是如此可耐受。”