Moderna and Merck announced positive topline results from their Phase 3 INTerpath-001 trial, showing that their personalized mRNA cancer vaccine, intismeran autogene (also known as V940 or mRNA-4157), significantly reduced the risk of melanoma recurrence and distant metastasis when used in combination with Merck's immunotherapy drug Keytruda. The trial met its primary endpoint of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS). These results mark a significant milestone as the first positive Phase 3 outcome for an individualized neoantigen therapy and an mRNA-based cancer treatment.
The INTerpath-001 trial enrolled 1,137 patients with completely resected stage IIB-IV melanoma who had not received prior systemic therapy. Patients were randomized to receive either intismeran autogene in combination with Keytruda, or Keytruda alone, for approximately one year. The companies stated that the improvements observed in RFS and DMFS were "statistically significant and clinically meaningful." While specific data were not disclosed, the combination therapy demonstrated a benefit over Keytruda alone in the adjuvant setting for resected melanoma. The trial observed no new safety signals, and the safety profile was consistent with previous studies.
Intismeran autogene is an individualized neoantigen therapy (INT) that uses a patient's tumor sample to identify unique mutations. The therapy then generates mRNA instructions to train the patient's immune system to recognize and attack cancer cells, targeting up to 34 neoantigens specific to the individual's tumor. This personalized approach aims to enhance the immune response against cancer.
These findings build upon earlier Phase 2b study results, KEYNOTE-942/mRNA-4157-P201, where the combination of intismeran autogene and Keytruda showed a 49% reduction in the risk of recurrence or death and a 59% reduction in the risk of distant metastasis or death compared to Keytruda alone after five years of follow-up. The Phase 2b study also indicated a positive trend toward improved overall survival (OS), though OS data matures over longer periods. The Phase 3 trial will continue to measure overall survival.
Moderna and Merck plan to present the detailed trial data at an upcoming international medical meeting and will engage with regulatory authorities regarding submission filings for intismeran autogene in combination with Keytruda. The companies had previously discussed seeking accelerated approval with regulators in 2024 based on Phase 2 data but were reportedly rebuffed by the FDA. The positive Phase 3 results are expected to strengthen their case for regulatory approval.
The success of this mRNA-based cancer vaccine has generated considerable excitement. Moderna's stock price surged significantly following the announcement. Analysts project billions of dollars in potential sales from the vaccine in melanoma alone. Beyond melanoma, the companies are also investigating this treatment approach in other cancers, including lung, kidney, and bladder cancer. This development could signal a new era for personalized cancer therapies and mRNA technology in oncology.