Phase 2 trial of axitinib plus avelumab for recurrent/metastatic adenoid cystic carcinoma: biomarker analysis and updated results

The phase 2 axitinib plus avelumab trial in recurrent/metastatic adenoid cystic carcinoma (ACC) demonstrated favorable response rate and progression-free survival (PFS). Biomarker analysis and updated results of the study have now been published. Twenty-eight patients were included. ACC comprises two proteogenomically distinct subtypes: the aggressive, NOTCH1-activated ACC-I and the more indolent ACC-II. The median PFS was 1.8 months for ACC-I versus 11.4 months for ACC-II (HR 0.14; p<0.0001). Clinical benefit was not associated with PD-L1 expression, tumor mutational burden, or recurrent genomic mutations. Improved PFS correlated with the presence of intratumoral Escherichia and gut Bifidobacterium and Akkermansia. Transcriptomic profiling identified a 167-gene immune-enriched signature predictive of benefit with axitinib plus avelumab. This signature also predicted benefit from ipilimumab plus nivolumab, but not from regorafenib monotherapy, suggesting its specificity for immunotherapy-based combinations. The authors conclude that outcomes with axitinib plus avelumab differ significantly by ACC subtype, whereas the identified signature predicts clinical benefit from immunotherapy-based combinations in ACC.