Merck and Moderna’s Phase 3 INTerpath-001 trial of intismeran autogene plus KEYTRUDA meets endpoints for recurrence-free survival and distant metastasis-free survival in patients with completely resected stage IIB-IV melanoma

First and only combination regimen to show statistically significant and clinically meaningful improvements in recurrence-free and distant metastasis-free survival compared with KEYTRUDA alone in the adjuvant melanoma setting for this patient group

Companies plan to present data at an upcoming international medical meeting and will engage with regulatory authorities on submissions for intismeran autogene combined with KEYTRUDA

Intismeran autogene is an mRNA-based individualized neoantigen therapy custom designed for each patient based on the specific mutations found in their tumor, intended to train and activate the immune system to recognize and fight cancer

Merck, known as MSD outside the United States and Canada, and Moderna, Inc. announced positive topline results from the Phase 3 INTerpath-001 trial evaluating adjuvant treatment with intismeran autogene (also known as intismeran, V940, or mRNA-4157), an investigational individualized neoantigen therapy jointly developed by the two companies, in combination with KEYTRUDA® (pembrolizumab), Merck’s anti-PD-1 therapy, in patients with completely resected stage IIB-IV melanoma. The trial achieved its primary endpoint of recurrence-free survival as well as a key secondary endpoint of distant metastasis-free survival. This marks the first positive Phase 3 result for an individualized neoantigen therapy and for an mRNA-based cancer treatment, and the first Phase 3 study to show a clinically meaningful improvement over KEYTRUDA alone, the current standard-of-care immunotherapy, in the adjuvant setting for patients with resected melanoma.

At a pre-specified interim analysis, the combination of intismeran and KEYTRUDA given as adjuvant therapy produced statistically significant and clinically meaningful improvements in both recurrence-free and distant metastasis-free survival compared with KEYTRUDA alone, among patients with completely resected stage IIB, IIC, III, or IV cutaneous melanoma who had not previously received systemic therapy. Per the trial protocol, the study will continue so that additional key secondary endpoints, including overall survival, can be evaluated.

The safety profiles of intismeran and KEYTRUDA observed in this trial were consistent with those reported in earlier studies of the combination, and no new safety signals emerged.

These findings are set to be presented at an upcoming international medical meeting and shared with regulatory authorities.

Professor Georgina Long, the study’s principal investigator, medical director of Melanoma Institute Australia, and chair of Melanoma Medical Oncology and Translational Research at the University of Sydney, called the results a landmark moment for adjuvant melanoma treatment. She said this is the first Phase 3 study to demonstrate that intismeran, a treatment built around the specific mutational profile of a patient’s own tumor, can reduce the risk of recurrence or death when combined with pembrolizumab compared with KEYTRUDA alone, in patients with completely resected stage IIB-IV melanoma. She said the combination has the potential to establish a new treatment standard in the adjuvant melanoma setting, helping more patients stay cancer-free for longer.

Dr. Dean Y. Li, president of Merck Research Laboratories, said that by intervening earlier in the course of disease, at a point when many cancers are considered most treatable, adjuvant therapy given after surgery aims to increase the chances of a cure for more patients. He said these first Phase 3 findings for intismeran combined with KEYTRUDA as adjuvant therapy reinforce the promise of a more personalized approach to cancer care, and that individualized neoantigen therapies have the potential to change how patients with completely resected stage IIB-IV melanoma are treated. He said Merck looks forward to presenting the INTerpath-001 data at an international medical meeting alongside Moderna and sharing it with regulators.

Stéphane Bancel, CEO of Moderna, described the Phase 3 findings as a pivotal moment for cancer research, noting that for many years the idea of building an mRNA treatment tailored to an individual patient’s cancer remained largely aspirational. He said Moderna, together with Merck, is now helping turn that vision into reality and has begun demonstrating the technology’s potential to address significant unmet needs in the adjuvant melanoma setting. He expressed gratitude to the patients, investigators, and study teams whose contributions made the progress possible.

Merck and Moderna continue to advance their broader INTerpath clinical development program, which is evaluating the safety and effectiveness of intismeran in combination with KEYTRUDA and other anticancer therapies, as well as on its own. The program currently includes nine Phase 2 and Phase 3 trials spanning multiple tumor types and disease stages, including melanoma, non-small cell lung cancer, bladder cancer, and renal cell carcinoma. Additional studies underway include the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma and a Phase 1 study examining adjuvant pancreatic ductal adenocarcinoma, perioperative gastric carcinoma, and perioperative non-small cell lung cancer.

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Related Topics and Keywords

KEYTRUDA, Merck, metastasis, Moderna, Phase 3 INTerpath-001 tria, Phase 3 INTerpath-001 trial, stage IIB-IV melanoma