Trial results for a Phase 3 study (NCT02224781) comparing sequencing of therapies in BRAFV600 melanoma were posted on ClinicalTrials.gov on 2026-02-18. The study investigated initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib versus the reverse sequence. Initial immunotherapy showed a 2-year overall survival (OS) of 68.3% compared to 54.1% for initial BRAF inhibitor therapy, with a p-value of 0.002.
Background
The study investigated treatment strategies for patients with Stage III-IV BRAFV600 melanoma. Specifically, it compared the sequence of initial immunotherapy (ipilimumab and nivolumab) followed by BRAF inhibitor therapy (dabrafenib and trametinib) against the reverse sequence. Ipilimumab and nivolumab are monoclonal antibodies that are thought to help the body's immune system attack cancer cells.
Trial design
The study (NCT02224781) was a Phase 3 trial that enrolled 267 participants. It investigated treatment for patients with Clinical Stage III Cutaneous Melanoma AJCC v8, Clinical Stage IV Cutaneous Melanoma AJCC v8, Metastatic Melanoma, Recurrent Melanoma, and Unresectable Melanoma that contains a BRAFV600 mutation. The trial compared two treatment sequences: Arm A received initial treatment with ipilimumab and nivolumab followed by dabrafenib and trametinib, while Arm B received initial treatment with dabrafenib and trametinib followed by ipilimumab and nivolumab.
Key results
The trial reported 2-year Overall Survival (OS) as a key measurement:
- For Arm A, which received initial immunotherapy (ipilimumab and nivolumab), the 2-year OS was 0.683 (proportion of participants).
- For Arm B, which received initial BRAF inhibitor therapy (dabrafenib and trametinib), the 2-year OS was 0.541 (proportion of participants).
A Log Rank analysis comparing the two treatment sequences yielded a p-value of 0.002.
What this means
The results suggest that for patients with Stage III-IV BRAFV600 melanoma, initiating treatment with ipilimumab and nivolumab before administering dabrafenib and trametinib may lead to a higher 2-year overall survival compared to the reverse sequence. The statistically significant p-value of 0.002 indicates a meaningful difference between the two treatment approaches, providing important data for clinicians considering optimal sequencing strategies for this patient population.
Source
The information regarding these trial results was obtained from ClinicalTrials.gov, a public database of clinical studies. The results for study NCT02224781, titled "Dabrafenib and Trametinib Followed by Ipilimumab and Nivolumab or Ipilimumab and Nivolumab Followed by Dabrafenib and Trametinib in Treating Patients With Stage III-IV BRAFV600 Melanoma," were posted on 2026-02-18 on clinicaltrials.gov.