Phase II SPARK trial results show objective responses when the tyrosine-kinase inhibitor sitravatinib is combined with the anti–PD-1 antibody tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC). Investigators report cohort-level activity in a hard-to-treat population and provide safety data from the multi-cohort, single-arm study. The trial positions sitravatinib’s modulation of the tumor microenvironment as a potential sensitizer for PD-1 blockade; investigators recommend further randomized study to define clinical benefit and patient selection biomarkers.