Merck and Moderna's Intismeran Meets Phase 3 Recurrence Goal in Resected Melanoma

Merck and Moderna said on August 19 that their Phase 3 INTerpath-001 trial of intismeran autogene, an investigational individualized mRNA therapy, given with Merck's Keytruda (pembrolizumab) met its primary endpoint of recurrence-free survival in patients with completely resected stage IIB-IV melanoma, according to the companies' announcement.

The trial also met a key secondary endpoint, distant metastasis-free survival. Both results came from a prespecified interim analysis comparing the combination with Keytruda alone as adjuvant therapy after surgery. The findings are company-reported topline results; the companies have not presented or published the data.

What the companies disclosed

Merck and Moderna said the combination produced statistically significant and clinically meaningful improvements in both endpoints. They did not disclose hazard ratios, absolute event rates, p-values or other efficacy estimates in the topline announcement, Practical Dermatology noted.

INTerpath-001 is a randomized, double-blind, placebo- and active-comparator-controlled global trial (NCT05933577). It enrolled 1,137 patients who, after complete surgical removal of their melanoma, were randomized 2:1 to intismeran at 1 mg every three weeks for up to nine doses plus Keytruda every six weeks, or to Keytruda alone, for about a year. Patients had not received prior systemic therapy. The study will continue to evaluate other key secondary endpoints, including overall survival, the companies said.

The safety profiles of intismeran and Keytruda were consistent with earlier studies of the combination, with no new safety signals, according to the announcement.

Intismeran, also known as V940 or mRNA-4157, is made for each patient from a sample of their tumor. Each dose is a synthetic mRNA coding for up to 34 neoantigens chosen from that tumor's mutations, intended to prompt an immune response against the cancer, the companies said.

"These Phase 3 findings represent a pivotal moment for the field of cancer research," said Stéphane Bancel, Moderna's chief executive.

Earlier data and next steps

The Phase 3 trial follows the Phase 2b KEYNOTE-942 study. At five-year follow-up, the combination was associated with a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death compared with Keytruda alone, Practical Dermatology reported.

Merck and Moderna said they plan to present INTerpath-001 data at an upcoming international medical meeting and will engage with regulators on filing submissions. The broader INTerpath program includes nine Phase 2 and Phase 3 trials in melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma, according to the companies. Intismeran is not approved for any use.