Clinical Summary: 

• Design/Population: The phase 3 INTerpath-001 trial evaluated intismeran, an individualized mRNA-based neoantigen therapy, plus pembrolizumab versus placebo plus pembrolizumab in patients with resected stage IIB to IV cutaneous melanoma.
• Key Outcomes: Intismeran plus pembrolizumab significantly improved recurrence-free survival and distant metastasis-free survival, reducing the risk of recurrence or death by 42% and distant metastasis or death by 38% compared with pembrolizumab alone. Benefits were observed across disease-stage subgroups.
• Clinical Relevance: These findings support the potential of individualized mRNA-based therapy to improve outcomes when added to adjuvant pembrolizumab in patients with resected high-risk melanoma.

Results from the phase 3 INTerpath-001 trial demonstrated that intismeran plus pembrolizumab significantly improved recurrence-free and distant metastasis-free survival in patients with resected stage IIB to IV cutaneous melanoma, supporting personalized mRNA-based immunotherapy as a promising adjuvant treatment approach.

These findings were presented by Georgina Long, MBBS, PhD, Melanoma Institute Australia, Wollstonecraft, Australia, during a Presidential Symposium at the European Society for Medical Oncology (ESMO) Congress.

In this double-blind trial, 1137 patients with surgically resected stage IIB/IIC or III/IV cutaneous melanoma were randomized 2:1 to receive 400 mg of pembrolizumab intravenously every 6 weeks for 9 cycles in combination with either 1 mg of intismeran (n = 757) or placebo (n = 380), administered intramuscularly every 3 weeks for 9 doses. Pembrolizumab was initiated at randomization, while intismeran or placebo was administered upon availability. 

The primary end point was recurrence-free survival (RFS). Key secondary end points included distant metastasis-free survival and safety. 

At a median follow-up of 24.6 months, 95.9% of patients in the intismeran plus pembrolizumab arm and 96.1% of patients in the placebo plus pembrolizumab arm had received at least 1 dose of their assigned intramuscular treatment.

The 24-month RFS rate was 82.2% in the intismeran plus pembrolizumab arm and 70% in the placebo plus pembrolizumab arm, reducing the risk of recurrence or death by 42% (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.45 to 0.75; P < .001). 

The 24-month distant metastasis-free survival rate was 88.5% in the intismeran plus pembrolizumab arm and 80.2% in the placebo plus pembrolizumab arm, reducing the risk of distant metastasis or death by 38% (HR, 0.62; 95% CI, 0.45 to 0.85; P = .002).

Improvements in RFS and distant metastasis-free survival were generally consistent across patient subgroups, including those with stage IIB to IIIB disease and stage IIIC to IV melanoma.

Grade ≥3 adverse events were reported in 23.6% of patients in the intismeran plus pembrolizumab arm and 20.3% of patients in the placebo plus pembrolizumab arm. The most frequently reported adverse events included pyrexia (52.2% vs 8.2%), injection-site pain (51% vs 9.5%), and fatigue (38.5% vs 29.7%). Adverse events led to simultaneous discontinuation of both study treatments in 6.5% and 5.3% of patients, respectively.

“These findings set a new benchmark for adjuvant melanoma and are a pivotal advance in personalized medicine and cancer treatment,” concluded Dr Long. 

Source: 

Long GV, et al. INTerpath-001: Phase 3 study of the mRNA-based individualized neoantigen therapy (INT) intismeran autogene (intismeran) plus pembrolizumab (pembro) vs pembro alone for adjuvant treatment of resected stage IIB-IV melanoma (MEL). Presented at ESMO Congress. October 23-27, 2026; Madrid, Spain. LBA1.