AACR 2026: Final Phase III Data Support Nivolumab Plus Ipilimumab for Patients With Metastatic Melanoma

By: Wendy LaGrego
Posted: Monday, May 4, 2026

Final 10-year results from the phase III NIBIT-M2 trial were presented at the 2026 American Association for Cancer Research (AACR) Annual Meeting by Anna Maria Di Giacomo, MD, PhD, of the Center for Immuno-Oncology, University Hospital of Siena, Siena, Italy, and colleagues. The trial evaluated long-term outcomes in patients with melanoma and asymptomatic brain metastases treated with immune checkpoint blockade.

Study Details

This multicenter study enrolled 80 patients between 2013 and 2018. Participants were randomly assigned 1:1:1 to receive fotemustine alone (Arm A), fotemustine plus ipilimumab (Arm B), or nivolumab plus ipilimumab (Arm C). With a median follow-up exceeding 10 years (125 months), the trial provides one of the longest longitudinal data sets in this difficult-to-treat population. The primary endpoint was overall survival, with secondary endpoints including intracranial progression-free survival, alongside exploratory analyses of cell-free DNA (cfDNA) metrics.

Key Takeaways

The results confirm a durable survival advantage with the dual immune checkpoint inhibition regimen. Median overall survival reached 29.2 months (95% confidence interval [CI] = 0–73.5 months) with nivolumab plus ipilimumab, compared with 8.5 months (95% CI = 4.8–12.2 months) in Arm A and 8.2 months (95% CI = 2.1–14.3 months) in Arm B. Notably, the 10-year overall survival rate was 31.2% (95% CI = 13.0%–49.4%) with the combination regimen, substantially higher than 13.0% (95% CI = 0%–26.7%) and 7.7% (95% CI = 0%–17.9%) observed with fotemustine alone and in combination with ipilimumab, respectively. Similarly, melanoma-specific survival at 10 years was 35.1% (95% CI = 16.3–53.9) in the nivolumab plus ipilimumab arm, compared with 13.0% and 7.7% in Arms A and B, respectively.

Beyond clinical outcomes, the investigators explored the prognostic value of plasma-derived biomarkers. Baseline levels of tumor fraction and tumor-specific methylation score (T-meth score) derived from cfDNA were associated with survival. Patients with lower baseline tumor fraction and T-meth scores experienced significantly longer overall survival compared with those above the median. Moreover, reductions in these biomarkers at 12 weeks correlated with improved outcomes.

The authors concluded: “The 10-year results of the NIBIT-M2 study, with the longest follow-up available to date in melanoma [patients] with asymptomatic [brain metastases], continue to show persistent long-term therapeutic efficacy of [ipilimumab plus nivolumab]. Plasma-derived [tumor fraction] and T-meth Score may predict long-term survival of melanoma [patients] with asymptomatic [brain metastases] treated with [ipilimumab plus nivolumab],” supporting their integration into future clinical strategies.

DISCLOSURE: For full disclosures of the study authors, visit abstractsonline.com.

AACR Annual Meeting 2026 (Abstract CT008)

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