Merck and Moderna’s individualized cancer therapy intismeran autogene combined with Keytruda reduced the risk of melanoma recurrence or death by 42% compared with Keytruda alone in the Phase 3 INTerpath-001 trial.
The randomized, double-blind study enrolled 1,137 patients with stage IIB-IV melanoma whose tumors had been completely removed surgically. Participants received either intismeran plus Keytruda or placebo plus Keytruda as postoperative treatment.
After median follow-up of 24.6 months, the combination met the primary recurrence-free survival endpoint, with a hazard ratio of 0.58 and a p-value below 0.001. At two years, 82.2% of combination recipients remained alive without recurrence, compared with 70% receiving Keytruda alone.
The combination also reduced the risk of distant metastasis or death by 38%. Two-year distant metastasis-free survival rates were 88.5% and 80.2%, respectively.
Treatment effects were comparable during the first six months. After that period, following the intismeran immunization regimen, a prespecified sensitivity analysis showed a 58% reduction in recurrence or death risk.
Overall survival data remain immature, and the trial continues to evaluate that endpoint. The companies are engaging with regulatory authorities.
Intismeran is an investigational messenger RNA therapy tailored to mutations in each patient’s tumor. It encodes up to 34 tumor-specific targets intended to train the immune system to recognize cancer cells.
Treatment-related adverse events occurred in 95.8% of combination recipients versus 90% with Keytruda alone. Grade 3-5 treatment-related events occurred in 14.2% and 13.4%, respectively. Fever, injection-site pain and fatigue were the combination’s most common adverse events. No new safety signals emerged, and findings were generally consistent with earlier studies.
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