KEYNOTE-942
Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma
Phase 2N = 157NCT03897881
- Population
- Patients with completely resected high-risk cutaneous melanoma (stage IIIB-IV)
- Design
- Open-label, randomised (2:1) phase 2b study. mRNA-4157 intramuscularly (maximum nine doses) plus pembrolizumab intravenously (maximum 18 doses) in 3-week cycles, versus pembrolizumab alone. Primary endpoint recurrence-free survival in the ITT population; sites in the USA and Australia. The 5-year update analyses were descriptive.
- Primary endpoint
- RFS
- Arms
- mRNA-4157 plus pembrolizumab (experimental, n = 107): mRNA-4157 (V940, intismeran autogene) intramuscularly, up to nine doses, plus pembrolizumab 200 mg intravenously, up to 18 doses
- Pembrolizumab (control, n = 50): Pembrolizumab 200 mg intravenously every 3 weeks, up to 18 doses
- People
- Weber JS, senior author Zaks T
RFSHR 0.561 (95% CI 0.309–1.017)Δ 18-month RFS+17 pointsRFSHR 0.510 (95% CI 0.294–0.887)DMFSHR 0.411 (95% CI 0.200–0.843)OSHR 0.471 (95% CI 0.165–1.345)
Show the numbers
| Endpoint | Analysis | mRNA-4157 plus pembrolizumab | Pembrolizumab | Effect |
|---|---|---|---|---|
| RFS | primaryWeber 2024 | 79% at 18 mo (69.0–85.6%) | 62% at 18 mo (46.9–74.3%) | HR 0.561 (95% CI 0.309–1.017)P=0.053 (two-sided)Median follow-up 23 months (combination) and 24 months (monotherapy). Recurrence or death in 24 (22%) of 107 vs 20 (40%) of 50. The 95% confidence interval of the hazard ratio includes 1. Grade 3 or higher treatment-related adverse events 25% vs 18%. |
| RFSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.510 (95% CI 0.294–0.887)Median planned follow-up 60.3 months (range 50.5 to 76.4) at the 15 December 2025 data cutoff. The abstract states the 5-year analyses were descriptive. |
| DMFSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.411 (95% CI 0.200–0.843)Secondary endpoint; descriptive analysis. |
| OSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.471 (95% CI 0.165–1.345)The 95% confidence interval includes 1; the abstract calls this a favourable trend. Descriptive analysis. |
| Endpoint | Analysis | mRNA-4157 plus pembrolizumab | Pembrolizumab | Effect |
|---|---|---|---|---|
| RFS | primaryWeber 2024 | 79% at 18 mo (69.0–85.6%) | 62% at 18 mo (46.9–74.3%) | HR 0.561 (95% CI 0.309–1.017)P=0.053 (two-sided)Median follow-up 23 months (combination) and 24 months (monotherapy). Recurrence or death in 24 (22%) of 107 vs 20 (40%) of 50. The 95% confidence interval of the hazard ratio includes 1. Grade 3 or higher treatment-related adverse events 25% vs 18%. |
| RFSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.510 (95% CI 0.294–0.887)Median planned follow-up 60.3 months (range 50.5 to 76.4) at the 15 December 2025 data cutoff. The abstract states the 5-year analyses were descriptive. |
| DMFSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.411 (95% CI 0.200–0.843)Secondary endpoint; descriptive analysis. |
| OSAll 157 randomised patients | long term-updatemedian follow-up 60.3 monthsKhattak 2026 | — | — | HR 0.471 (95% CI 0.165–1.345)The 95% confidence interval includes 1; the abstract calls this a favourable trend. Descriptive analysis. |
Data table
| Endpoint | HR | 95% CI |
|---|---|---|
| RFS | 0.561 | 0.309–1.017 |
| RFS | 0.51 | 0.294–0.887 |
| DMFS | 0.411 | 0.2–0.843 |
| OS | 0.471 | 0.165–1.345 |
Appears in
Sources
Weber JS, Carlino MS, Khattak A, Meniawy T, Ansstas G, Taylor MH, et al. Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study. Lancet. 2024;403(10427):632-644.
Khattak A, Carlino MS, Meniawy T, Ansstas G, Taylor MH, Kim KB, et al. Intismeran Autogene Plus Pembrolizumab Versus Pembrolizumab Alone in High-Risk Resected Melanoma: 5-Year Update of the Randomized Phase IIb KEYNOTE-942 Study. J Clin Oncol. 2026;44(26):2482-2489.