Nivolumab Plus Low-Dose Ipilimumab Shows Promise in Hypermutated HER2-Negative Metastatic Breast Cancer

In the phase II NIMBUS trial, HER2-negative metastatic breast cancer (MBC) patients with high tumor mutational burden (TMB ≥9 mut/Mb) received nivolumab and low-dose ipilimumab, achieving an overall objective response rate of 20%. Notably, patients with TMB ≥14 mut/Mb had a significantly higher response rate of 60% compared to 12% in those with lower TMB, along with trends toward better progression-free and overall survival. Exploratory analyses also identified ESR1 and PTEN mutations as potential markers for poor response, while early decreases in circulating tumor DNA and distinct microbiome profiles were linked to clinical benefit, underscoring a multifaceted biomarker approach.

These findings highlight the potential of dual immunotherapy as a targeted strategy in hypermutated HER2-negative MBC, suggesting that higher TMB, complemented by genomic and microbiome markers, could help identify patients most likely to benefit from this regimen.