Merck and Moderna reported positive topline results from the Phase 3 INTerpath-001 trial of intismeran autogene combined with Keytruda in patients with completely resected stage IIB through IV melanoma.
The study met its primary endpoint of recurrence-free survival and a key secondary endpoint of distant metastasis-free survival. In a prespecified interim analysis, the combination showed statistically significant and clinically meaningful improvements on both measures compared with Keytruda alone, the companies said.
The trial enrolled 1,137 patients with high-risk cutaneous melanoma who had undergone complete surgical resection and had not received prior systemic therapy. Participants were randomly assigned two-to-one to receive intismeran plus Keytruda or Keytruda alone.
Patients in the combination arm received 1 mg of intismeran every three weeks for up to nine doses and 400 mg of Keytruda every six weeks for up to nine cycles. Treatment continued for about one year, until recurrence, unacceptable toxicity or a maximum treatment duration of roughly 56 weeks.
Intismeran, also known as V940 or mRNA-4157, is an investigational mRNA-based individualized neoantigen therapy. It is designed using each patient’s tumor sample to identify the tumor’s specific mutations and create a treatment coding for up to 34 neoantigens. The goal is to train the immune system to recognize and attack cancer cells.
The companies said the safety profile of intismeran plus Keytruda was consistent with prior studies of the combination, with no new safety signals observed. The trial will continue to evaluate other key secondary endpoints, including overall survival.
Merck and Moderna plan to present the findings at an upcoming international medical meeting and discuss potential regulatory submissions with health authorities.
The Phase 3 results build on earlier Phase 2b data from the KEYNOTE-942/mRNA-4157-P201 trial. At five years, that study showed a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death for the combination compared with Keytruda alone.
The companies said INTerpath is evaluating intismeran across nine Phase 2 and Phase 3 trials in melanoma, non-small cell lung cancer, bladder cancer and renal cell carcinoma. Intismeran remains investigational and has not been approved for any use.
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