Conference Coverage

Intismeran Plus Pembrolizumab Shows Durable 5-Year Benefit in High-Risk Resected Melanoma

Edited by:
Ashton L. Stahl

Key Highlights

  • Intismeran plus pembrolizumab reduced recurrence-free survival (RFS) risk by 49% vs pembrolizumab alone.
  • 5-year RFS was 68.8% with combination therapy vs 49.1% with pembrolizumab.
  • Distant metastasis-free survival risk was reduced by 59%, and OS showed a trend favoring the combination.

Intismeran autogene plus pembrolizumab continued to show durable benefit at 5 years in patients with high-risk resected melanoma, according to updated results from the phase 2b KEYNOTE-942 study published as a 2026 American Society of Clinical Oncology Annual Meeting abstract in the Journal of Clinical Oncology. The analysis reported sustained improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS), along with a trend toward improved overall survival (OS), compared with pembrolizumab alone.

The study enrolled adults aged 18 years or older with resected stage IIIB to IV cutaneous melanoma. Participants were randomized 2:1 to receive 9 doses of intismeran 1 mg intramuscularly every 3 weeks plus 18 doses of pembrolizumab 200 mg intravenously every 3 weeks, or pembrolizumab 200 mg every 3 weeks alone. The primary endpoint was RFS; secondary endpoints included DMFS and safety. OS was an exploratory endpoint, and no alpha was assigned to this analysis.

Study Findings

Between July 2019 and September 2021, 157 participants were randomized to intismeran plus pembrolizumab (n = 107) or pembrolizumab alone (n = 50). At the December 15, 2025, data cutoff, the median planned follow-up was 60.3 months, with a range of 50.5 to 76.4 months. Investigators reported that minimal new events occurred after the prior 3-year analysis.

The combination reduced the risk of RFS events by 49% compared with pembrolizumab alone (HR, 0.51; 95% CI, 0.29-0.89). Landmark 5-year RFS rates were 68.8% (95% CI, 56.3%-78.3%) with intismeran plus pembrolizumab and 49.1% (95% CI, 33.3%-63.0%) with pembrolizumab alone.

For DMFS, intismeran plus pembrolizumab reduced risk by 59% vs pembrolizumab alone (HR, 0.41; 95% CI, 0.20-0.84). In the combination arm, 7 participants (6.5%) died, including 4 deaths attributed to disease progression. In the pembrolizumab arm, 7 participants (14%) died, including 6 deaths attributed to disease progression.

OS showed a trend favoring intismeran plus pembrolizumab (HR, 0.47; 95% CI, 0.17-1.35). The 5-year OS rate was 92.2% (95% CI, 84.2%-96.3%) in the combination group and 71.3% (95% CI, 35.4%-89.6%) in the pembrolizumab group. The safety profile of intismeran was consistent with prior analyses.

Clinical Implications

According to the study authors, these long-term findings show that the treatment benefits with intismeran plus pembrolizumab were sustained and durable, despite all participants having completed study treatment before the primary analysis in 2021. The authors also noted that intismeran plus pembrolizumab is being evaluated in the phase 3 INTerpath-001 study in high-risk resected stage II to IV melanoma, as well as in studies of other malignancies.

Expert Commentary

“After a median 5 y[ear] of follow-up, intismeran [combined with] pembro[lizumab] continued to prolong RFS and DMFS,” the researchers concluded.

Reference

Carlino MS, Khattak A, Meniawy T, et al. Individualized neoantigen therapy intismeran autogene plus pembrolizumab in resected melanoma: 5-year update of the KEYNOTE-942 study. J Clin Oncol. 2026;44(suppl 16):9500. doi:10.1200/JCO.2026.44.16_suppl.9500