PRADO
Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma (PRADO extension cohort of OpACIN-neo)
Phase 2N = 99NCT02977052
- Population
- Patients with clinical stage IIIb-d nodal melanoma
- Design
- Single-arm extension cohort of OpACIN-neo (ClinicalTrials.gov NCT02977052). Six weeks of neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg. Patients with a major pathologic response (10% or less viable tumour) in the index lymph node omitted therapeutic lymph node dissection and adjuvant therapy; partial responders (more than 10% to 50% viable tumour) had dissection only; nonresponders (more than 50%) had dissection and adjuvant systemic therapy, with or without radiotherapy.
- Arms
- Neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg, response-directed (experimental, n = 99): Six weeks of neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg, then response-directed surgery and adjuvant therapy
- People
- Reijers ILM, senior author Blank CU
Show the numbers
| Endpoint | Analysis | Neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg, response-directed | Control | Effect |
|---|---|---|---|---|
| Pathological response rateAll 99 patients treated | primaryReijers 2022 | 72% | — | Pathological response rate 72%, of which 61% was major pathologic response. Grade 3-4 toxicity within the first 12 weeks in 22 (22%) patients. Therapeutic lymph node dissection was omitted in 59 of 60 patients with major pathologic response. |
| RFSPatients with major pathologic response | primaryReijers 2022 | 93% at 2 y | — | Response-defined subgroup, not a randomised comparison. 24-month distant metastasis-free survival 98%. |
| RFSPatients with pathologic partial response | exploratoryReijers 2022 | 64% at 2 y | — | Response-defined subgroup, not a randomised comparison. 24-month distant metastasis-free survival 64%. |
| RFSPatients with pathologic nonresponse | primaryReijers 2022 | 71% at 2 y | — | Response-defined subgroup, not a randomised comparison. These patients received dissection and adjuvant systemic therapy. 24-month distant metastasis-free survival 76%. |
| EFSAll 99 patients treated | long term-updateHoeijmakers 2026 | 71% at 5 y | — | First 5-year survival report for the PRADO cohort (phase 2, single arm). 5-year relapse-free survival 74%, distant metastasis-free survival 79%, overall survival 86% (all as published without intervals in the abstract). |
| OSAll 99 patients treated | long term-updateHoeijmakers 2026 | 86% at 5 y | — | Single-arm cohort; no comparator. |
| Endpoint | Analysis | Neoadjuvant ipilimumab 1 mg/kg plus nivolumab 3 mg/kg, response-directed | Control | Effect |
|---|---|---|---|---|
| Pathological response rateAll 99 patients treated | primaryReijers 2022 | 72% | — | Pathological response rate 72%, of which 61% was major pathologic response. Grade 3-4 toxicity within the first 12 weeks in 22 (22%) patients. Therapeutic lymph node dissection was omitted in 59 of 60 patients with major pathologic response. |
| RFSPatients with major pathologic response | primaryReijers 2022 | 93% at 2 y | — | Response-defined subgroup, not a randomised comparison. 24-month distant metastasis-free survival 98%. |
| RFSPatients with pathologic partial response | exploratoryReijers 2022 | 64% at 2 y | — | Response-defined subgroup, not a randomised comparison. 24-month distant metastasis-free survival 64%. |
| RFSPatients with pathologic nonresponse | primaryReijers 2022 | 71% at 2 y | — | Response-defined subgroup, not a randomised comparison. These patients received dissection and adjuvant systemic therapy. 24-month distant metastasis-free survival 76%. |
| EFSAll 99 patients treated | long term-updateHoeijmakers 2026 | 71% at 5 y | — | First 5-year survival report for the PRADO cohort (phase 2, single arm). 5-year relapse-free survival 74%, distant metastasis-free survival 79%, overall survival 86% (all as published without intervals in the abstract). |
| OSAll 99 patients treated | long term-updateHoeijmakers 2026 | 86% at 5 y | — | Single-arm cohort; no comparator. |
Appears in
Sources
Reijers ILM, Menzies AM, van Akkooi ACJ, Versluis JM, van den Heuvel NMJ, Saw RPM, et al. Personalized response-directed surgery and adjuvant therapy after neoadjuvant ipilimumab and nivolumab in high-risk stage III melanoma: the PRADO trial. Nat Med. 2022;28(6):1178-1188.
Hoeijmakers LL, Dimitriadis P, Wijnen SCMA, Reijers ILM, Lopez-Yurda M, Menzies AM, et al. Neoadjuvant ipilimumab plus nivolumab in melanoma: 5-year survival and biomarker analysis from the phase 2 PRADO-trial. Nat Med. 2026;32(3):952-963.