Skip to content
Bending the Curve Trial by Trial
?

EBIN

Immunotherapy With Ipilimumab and Nivolumab Preceded or Not by a Targeted Therapy With Encorafenib and Binimetinib

Phase 2N = 271NCT03235245

Population
Previously untreated unresectable stage III or IV melanoma with BRAF V600E or V600K mutations, ECOG performance status 0 or 1
Design
Open-label randomised (1:1) phase 2 trial at 37 centres in eight European countries: encorafenib plus binimetinib for 12 weeks followed by ipilimumab and nivolumab (induction group) versus ipilimumab and nivolumab without induction (control group). Primary end point progression-free survival in the intention-to-treat population; the paper reports the primary analysis.
Primary endpoint
PFS
Arms
  • Targeted induction then ipilimumab and nivolumab (experimental, n = 136): Encorafenib 450 mg once daily plus binimetinib 45 mg twice daily for 12 weeks, then nivolumab 3 mg per kilogram plus ipilimumab 1 mg per kilogram every 3 weeks for four doses, then nivolumab 480 mg every 4 weeks
  • Ipilimumab and nivolumab (control, n = 135): Nivolumab 3 mg per kilogram plus ipilimumab 1 mg per kilogram every 3 weeks for four doses, then nivolumab 480 mg every 4 weeks
People
Robert C, senior author van Akkooi ACJ
Δ median PFS0 months
Show the numbers
Results reported for EBIN
EndpointAnalysisTargeted induction then ipilimumab and nivolumabIpilimumab and nivolumabEffect
PFSprimarymedian follow-up 21 monthsRobert 2025median 9 months (7–13)median 9 months (5–14)P=0.36Hazard ratio 0.87 with a 90% confidence interval of 0.67 to 1.12, as published. The abstract states there was no evidence of longer progression-free survival with induction. Grade 3 to 5 treatment-related adverse events: 42% versus 32%.
Results reported for EBIN
EndpointAnalysisTargeted induction then ipilimumab and nivolumabIpilimumab and nivolumabEffect
PFSprimarymedian follow-up 21 monthsRobert 2025median 9 months (7–13)median 9 months (5–14)P=0.36Hazard ratio 0.87 with a 90% confidence interval of 0.67 to 1.12, as published. The abstract states there was no evidence of longer progression-free survival with induction. Grade 3 to 5 treatment-related adverse events: 42% versus 32%.
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%05101520Months (modelled)
  • Targeted induction then ipilimumab and nivolumab (experimental)
  • Ipilimumab and nivolumab (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsTargeted induction then ipilimumab and nivolumabIpilimumab and nivolumab
0100.0%100.0%
663.0%63.0%
1142.9%42.9%
1727.0%27.0%
2317.0%17.0%
Primary publication: Robert C, Kicinski M, Dutriaux C, Routier É, Govaerts AS, Bührer E, et al. Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAF(V600E) or BRAF(V600K) mutations (EBIN): an international, open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2025;26(6):781-794. PubMedDOI

Appears in

Sources

  1. Robert C, Kicinski M, Dutriaux C, Routier É, Govaerts AS, Bührer E, et al. Combination of encorafenib and binimetinib followed by ipilimumab and nivolumab versus ipilimumab and nivolumab in patients with advanced melanoma with BRAF(V600E) or BRAF(V600K) mutations (EBIN): an international, open-label, randomised, controlled, phase 2 study. Lancet Oncol. 2025;26(6):781-794.

    PubMedDOI