On August 19, 2026, Moderna and Merck (known as MSD outside the U.S. and Canada) announced that their jointly developed, world's first personalized mRNA cancer vaccine, intismeran autogene (V940 / mRNA-4157), when used together with pembrolizumab (KEYTRUDA®) as adjuvant therapy for completely completely resected high-risk stage IIB, IIC, III, or IV cutaneous melanoma, the Ⅲ INTerpath-001 trial in a pre-specified interim analysis met the primary endpoint of recurrence-free survival (RFS) and the key secondary endpoint of distant metastasis-free survival (DMFS).

This is a global, randomized, double-blind, placebo- and active-comparator-controlled Ⅲ study that enrolled 1137 patients who had undergone complete surgical resection and had not received prior systemic therapy, randomized in a 2:1 ratio to the combination treatment group or the KEYTRUDA monotherapy control group. The combination regimen significantly prolonged the time patients remained recurrence-free and distant metastasis-free after surgery, achieving statistically significant and clinically meaningful improvements. Per the trial protocol, the study will continue to evaluate other key secondary endpoints, including overall survival (OS), for which data are currently immature. In terms of safety, the safety profile of intismeran in combination with KEYTRUDA was consistent with previously reported studies, with no new safety signals observed.

This represents the first individualized neoantigen therapy (INT) to achieve positive results in a Ⅲ clinical trial in human history, the first positive Ⅲ readout for an mRNA-based cancer therapy, and the first Ⅲ study to demonstrate a clinically meaningful improvement over standard-of-care KEYTRUDA monotherapy in the adjuvant melanoma setting, marking the first successful Ⅲ trial for mRNA technology in cancer treatment.

Traditional PD-1 monotherapy primarily relieves T-cell immunosuppression, whereas intismeran autogene is based on whole-exome and RNA sequencing of the patient's tumor, algorithmically selected to encode up to 34 patient-specific neoantigens, providing the immune system with more targeted anti-tumor targets. The combination means tumor immunotherapy evolves from simply "releasing the brakes" to "releasing the brakes + targeted immune response supplementation." In plain terms, when mRNA containing up to 34 personalized neoantigen sequences enters human cells, the body's immune factory immediately translates them into neoantigen protein fragments and presents them to the immune system. T cells in the body, upon seeing these fragments, rapidly complete "special forces training" and begin patrolling throughout the body's blood vessels and lymphatic vessels, specifically killing cancer cells carrying these mutational signatures. Each patient's vaccine is individually designed based on their tumor's mutational signature, which is why it is called an INT.

The specific treatment regimen is: intismeran autogene 1 mg intramuscularly, every 3 weeks, up to 9 doses; in combination with KEYTRUDA 400 mg intravenously, every 6 weeks, up to 9 cycles (approximately one year). The control group received KEYTRUDA monotherapy for approximately one year, until disease recurrence or unacceptable toxicity, with a total treatment duration of up to approximately 56 weeks.

The current Ⅲ positive results build on data from the Phase 2b KEYNOTE-942/mRNA-4157-P201 study. The 5-year follow-up data from this study were presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting: intismeran in combination with KEYTRUDA, compared to KEYTRUDA monotherapy, reduced the risk of recurrence or death by 49% (hazard ratio [HR]=0.51; 95% confidence interval [CI], 0.294–0.887), and reduced the risk of distant metastasis or death by 59% (HR=0.411; 95% CI, 0.200–0.843); the 5-year RFS rates were 68.8% (95% CI, 56.3%–78.3%) and 49.1% (95% CI, 37.0%–60.2%), respectively.

Merck and Moderna plan to formally present the detailed data of INTerpath-001 at an upcoming top international medical conference, and will engage with regulatory authorities on marketing authorization submissions. Moderna Chief Executive Officer (CEO) Stéphane Bancel stated that the personalized cancer vaccine could be approved for marketing as early as 2027, depending on the regulatory review process.

This is not only an important clinical validation of mRNA technology in oncology, but also opens the path for individualized immunotherapy to become the backbone of next-generation immuno-oncology combinations. Merck and Moderna's INTerpath pipeline currently comprises 9 Phase 2 and Ⅲ clinical trials, spanning multiple tumor types and disease stages including melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma; additional Phase 1 studies are exploring adjuvant pancreatic ductal adenocarcinoma, perioperative gastric cancer, and perioperative NSCLC. This pipeline is expected to form another scalable tumor treatment platform following PD-1 and antibody-drug conjugates (ADCs).

The era of precision anti-cancer treatment for humanity is becoming a reality!

I. Original Source

This article is adapted from "Major Breakthrough: The First Therapeutic Cancer Vaccine!" published by Sina Finance on August 20, 2026 (content source: Shezhang Shuo / Yanxun She).

II. Data Sources

[1] ClinicalTrials.gov. INTerpath-001 (NCT05933577): A Study of Intismeran Autogene in Combination With Pembrolizumab Versus Pembrolizumab Alone in Participants With completely resected high-risk Stage IIB-IV Melanoma.

[2] Merck & Moderna. Merck and Moderna Announce Ⅲ INTerpath-001 Trial of Intismeran Autogene Plus KEYTRUDA Met Endpoints of RFS and DMFS in Patients With Completely Resected Stage IIB-IV Melanoma. Official joint press release, 2026-08-19. https://www.nasdaq.com/press-release/merck-and-moderna-announce-phase-3-interpath-001-trial-intismeran-autogene-plus

[3] Merck. Moderna & Merck Announce 5-Year Data for Intismeran Autogene in Combination With KEYTRUDA in KEYNOTE-942 Trial. Official announcement, 2026-01-20. https://www.merck.com/news/moderna-merck-announce-5-year-data-for-intismeran-autogene-in-combination-with-keytruda-pembrolizumab-demonstrated-sustained-improvement-in-the-primary-endpoint-of-recurrence-free-survival-i/

[4] Long GI, et al. Individualized neoantigen therapy intismeran autogene plus pembrolizumab in resected melanoma: 5-year update of the KEYNOTE-942 study. J Clin Oncol 2026;44(16_suppl):9500. ASCO 2026 Annual Meeting abstract. https://ascopubs.org/doi/10.1200/JCO.2026.44.16_suppl.9500

[5] Moderna (MRNA) US stock market data. Close at 16:00 ET on 2026-08-19. Tonghuashun / Sina Finance / Xueqiu. https://stock.finance.sina.com.cn/usstock/quotes/mrna.html

[6] Sina Finance. When will Moderna's personalized cancer vaccine be available on the market? 2026-08-20. https://cj.sina.com.cn/articles/view/7879849019/1d5acf43b06801dwu6

Note: Trial registration information in this article is sourced from reference [1]; INTerpath-001 Ⅲ trial design, endpoint results, safety conclusions, dosing regimen, and pipeline information are sourced from reference [2]; KEYNOTE-942 Phase 2b 5-year follow-up data are sourced from references [3][4]; stock price and market capitalization data are sourced from reference [5]; marketing timeline expectations are sourced from reference [6].