OpACIN-neo
Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma
Phase 2N = 89NCT02977052
- Population
- Adults with resectable stage III melanoma involving lymph nodes only and measurable disease (RECIST 1.1), WHO performance status 0 to 1
- Design
- Multicentre, open-label, randomised (1:1:1) phase 2 trial in three centres in Australia, Sweden and the Netherlands. Three neoadjuvant dosing schedules; analyses in all patients who received at least one dose. 89 patients were randomised; 3 were excluded as ineligible, and 86 received study drug. Group C accrual closed early on advice of the Data Safety Monitoring Board because of severe adverse events.
- Primary endpoint
- Grade 3-4 immune-related adverse events, ORR, Pathological response rate
- Arms
- Group A (control, n = 30): Two cycles of ipilimumab 3 mg/kg plus nivolumab 1 mg/kg every 3 weeks
- Group B (experimental, n = 30): Two cycles of ipilimumab 1 mg/kg plus nivolumab 3 mg/kg every 3 weeks
- Group C (experimental, n = 26): Two cycles of ipilimumab 3 mg/kg every 3 weeks, followed by two cycles of nivolumab 3 mg/kg every 2 weeks
- People
- Rozeman EA, senior author Blank CU
Δ Grade 3-4 immune-related adverse events−20 pointsΔ ORR−6 pointsΔ Pathological response rate−3 points
Show the numbers
| Endpoint | Analysis | Group B / Group C | Group A | Effect |
|---|---|---|---|---|
| Grade 3-4 immune-related adverse eventsPatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 20% | 40% | Within the first 12 weeks. Difference group B vs A -20% (95% CI -46 to 6; p=0.158); group C vs A 10% (-20 to 40; p=0.591). One patient in group A died 9.5 months after starting treatment of late-onset immune-related encephalitis, possibly treatment-related. |
| ORRPatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 57% (37–75%) | 63% (44–80%) | Radiological objective response at 6 weeks (RECIST 1.1). |
| Pathological response ratePatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 77% (58–90%) | 80% (61–92%) | Pathological response at 6 weeks. The trial did not test efficacy differences between schedules formally; the aim was a schedule that is less toxic but equally effective. |
| Endpoint | Analysis | Group B / Group C | Group A | Effect |
|---|---|---|---|---|
| Grade 3-4 immune-related adverse eventsPatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 20% | 40% | Within the first 12 weeks. Difference group B vs A -20% (95% CI -46 to 6; p=0.158); group C vs A 10% (-20 to 40; p=0.591). One patient in group A died 9.5 months after starting treatment of late-onset immune-related encephalitis, possibly treatment-related. |
| ORRPatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 57% (37–75%) | 63% (44–80%) | Radiological objective response at 6 weeks (RECIST 1.1). |
| Pathological response ratePatients who received at least one dose (30, 30 and 26) | primaryRozeman 2019 | 77% (58–90%) | 80% (61–92%) | Pathological response at 6 weeks. The trial did not test efficacy differences between schedules formally; the aim was a schedule that is less toxic but equally effective. |
Appears in
Sources
Rozeman EA, Menzies AM, van Akkooi ACJ, Adhikari C, Bierman C, van de Wiel BA, et al. Identification of the optimal combination dosing schedule of neoadjuvant ipilimumab plus nivolumab in macroscopic stage III melanoma (OpACIN-neo): a multicentre, phase 2, randomised, controlled trial. Lancet Oncol. 2019;20(7):948-960.