mRNA cancer vaccine succeeded in Phase 3 melanoma trial, Moderna and Merck say

Moderna 和默沙东宣布：mRNA 癌症疫苗在黑色素瘤三期临床试验中取得成功

Pharmaceutical partners Moderna and Merck announced on Wednesday that their novel mRNA-based vaccine—individually tailored to target a patient’s unique cancer mutations—was effective in a late-stage clinical trial of patients with melanoma, one of the deadliest forms of skin cancer. 制药合作伙伴 Moderna 和默沙东（Merck）周三宣布，他们研发的一种新型 mRNA 疫苗在针对黑色素瘤（最致命的皮肤癌之一）的后期临床试验中表现出疗效。该疫苗是为患者量身定制的，旨在靶向患者独特的癌症突变。

The announcement was scant on details, but if the success holds, it stands to realize the high aspirations for both mRNA vaccines and individualized cancer-targeting medicines in cancer therapy, providing a first success for both treatment types. 虽然此次公告提供的细节有限，但如果这一成功经得起验证，它将实现 mRNA 疫苗和个性化癌症靶向药物在癌症治疗领域的高远目标，并为这两种治疗方式带来首次成功。

The Phase 3 trial included 1,137 patients who had stage IIB–IV melanoma that had been surgically removed prior to their treatment in the trial. Patients were randomized 2-1 to receive either a combination treatment of the tailored mRNA vaccine (intismeran or mRNA-4157) with Merck’s established monoclonal antibody cancer treatment Keytruda, or they received treatment with Keytruda alone. Both patient groups were treated for about a year. The trial was placebo-controlled and double-blind, meaning neither the doctors nor the patients knew which treatment patients were randomly assigned to receive. 这项三期试验纳入了 1,137 名患者，他们均患有 IIB 至 IV 期黑色素瘤，且在试验治疗前已通过手术切除肿瘤。患者以 2:1 的比例被随机分配，一组接受定制 mRNA 疫苗（intismeran 或 mRNA-4157）与默沙东已上市的单克隆抗体癌症药物 Keytruda 的联合治疗，另一组仅接受 Keytruda 单药治疗。两组患者均接受了约一年的治疗。该试验采用安慰剂对照和双盲设计，这意味着医生和患者都不知道患者被随机分配到了哪种治疗方案。

Based on a planned interim analysis, Moderna and Merck report that the combination therapy with the mRNA vaccine extended “recurrence-free survival” (RFS), which is the amount of time a patient has without the cancer returning. The combination therapy also extended “distant metastasis-free survival” (DMFS), which is the amount of time a patient has without the cancer returning and occurring in a different part of the body than where it began. 根据计划的中期分析，Moderna 和默沙东报告称，mRNA 疫苗联合疗法延长了“无复发生存期”（RFS），即患者在癌症不复发的情况下生存的时间。该联合疗法还延长了“无远处转移生存期”（DMFS），即患者在癌症不复发且未扩散至身体其他部位的情况下生存的时间。

The companies say the extensions of RFS and DMFS reported were statistically significant and clinically meaningful, but they did not elaborate. They said the data will be presented at an upcoming international medical conference. They did note, however, that data from a five-year Phase 2 trial, which was presented at a cancer researcher conference in June, showed a 49 percent reduction in the risk of recurrence or death and a 59 percent reduction in the risk of distant metastasis or death. 两家公司表示，所报告的 RFS 和 DMFS 的延长在统计学上具有显著性，在临床上具有意义，但未作详细说明。他们表示，数据将在即将召开的国际医学会议上公布。不过，他们确实提到，6 月份在癌症研究会议上公布的一项为期五年的二期试验数据显示，复发或死亡风险降低了 49%，远处转移或死亡风险降低了 59%。

The mRNA vaccine intismeran works using a synthetic mRNA that holds the unique genetic coding for up to 34 mutations in a patient’s own cancer cells. The production process involves comparing the genetic sequences of a patient’s cancer cells to those of healthy cells and picking out any cancer-specific mutations that could help the immune system differentiate cancer cells from healthy ones. mRNA 疫苗 intismeran 的工作原理是利用合成 mRNA，其中包含患者自身癌细胞中多达 34 种突变的独特遗传编码。生产过程包括将患者癌细胞的基因序列与健康细胞的基因序列进行比较，并筛选出有助于免疫系统区分癌细胞和健康细胞的癌症特异性突变。

Using the same platform Moderna used for its mRNA COVID-19 vaccine, intismeran delivers to healthy cells the mRNA code for those mutations. Healthy cells translate that mRNA code into protein fragments representing the cancer mutations, and then those fragments are presented to immune cells as antigens, a foreign substance to attack. As such, Moderna and Merck call their mRNA cancer vaccine a type of “neoantigen therapy.” intismeran 使用了 Moderna 用于其新冠 mRNA 疫苗的相同平台，将这些突变的 mRNA 编码递送至健康细胞。健康细胞将这些 mRNA 编码翻译成代表癌症突变的蛋白质片段，然后这些片段作为抗原（一种需要攻击的异物）呈递给免疫细胞。因此，Moderna 和默沙东将他们的 mRNA 癌症疫苗称为一种“新抗原疗法”。

In the companies’ announcement, Georgina Long, who led the trial, said the results were “a landmark moment” with the “potential to establish a new treatment paradigm.” Dean Li, president of Merck Research Laboratories, said the findings “reinforce the promise of a more personalized approach to cancer treatment.” Moderna CEO Stéphane Bancel, meanwhile, highlighted mRNA technology’s role, saying this is “a pivotal moment for the field of cancer research.” 在两家公司的公告中，领导该试验的 Georgina Long 表示，这些结果是一个“里程碑时刻”，具有“建立新治疗范式的潜力”。默沙东研究实验室总裁 Dean Li 表示，这些发现“加强了癌症治疗向更个性化方向发展的承诺”。与此同时，Moderna 首席执行官 Stéphane Bancel 强调了 mRNA 技术的作用，称这是“癌症研究领域的关键时刻”。

“For many years, the idea of creating an mRNA treatment designed specifically for an individual patient’s cancer was aspirational. We are now helping turn that vision into a reality,” Bancel said. Bancel 说：“多年来，为个体患者的癌症专门设计 mRNA 疗法的想法一直是一个愿景。我们现在正在帮助将这一愿景变为现实。”

Despite the lack of details, outside experts are similarly hopeful and encouraged by the announcement. “This is the first positive Phase III trial of an individualized neoantigen therapy and an mRNA-based cancer treatment,” University of Oxford cancer expert Lennard Lee said in a statement. “That makes this an important moment for a field that scientists have been working towards for many years. Within six years of the pandemic, we have mRNA vaccines to treat cancer,” he said, also calling it “very encouraging” and “significant.” 尽管缺乏细节，但外部专家对这一公告同样感到充满希望和鼓舞。牛津大学癌症专家 Lennard Lee 在一份声明中表示：“这是个性化新抗原疗法和基于 mRNA 的癌症治疗的首个阳性三期试验。这使得这一领域迎来了一个重要时刻，科学家们为此已经努力多年。在疫情发生后的六年内，我们就拥有了治疗癌症的 mRNA 疫苗。”他称这一进展“非常令人鼓舞”且“意义重大”。

Lee, however, highlighted that we don’t yet know the magnitude of the benefit, the detailed subgroup analyses, quality-of-life data, or mature overall-survival results. “Those details will allow the scientific and clinical community to understand precisely how large the benefit is, which patients benefit most, and ultimately where this treatment might sit within routine melanoma care,” he said. 然而，Lee 强调，我们尚不清楚获益的程度、详细的亚组分析、生活质量数据或成熟的总生存期结果。“这些细节将使科学界和临床界能够准确了解获益有多大，哪些患者获益最多，以及这种疗法最终在常规黑色素瘤护理中处于什么位置，”他说。