Phase 2 trial of sitravatinib plus tislelizumab in locally recurrent or metastatic triple-negative breast cancer

The phase 2 SPARK trial, at Fudan University (Shanghai, China), evaluated the combination of the multi-target TKI sitravatinib and the anti-PD-1 monoclonal antibody tislelizumab in patients with locally recurrent or metastatic triple-negative breast cancer (TNBC). The trial enrolled 67 patients, with 38 having one or more previous systemic therapy. Patients in cohort A received sitravatinib 70 mg once daily plus tislelizumab; patients in cohort B received sitravatinib 100 mg once daily plus tislelizumab. The primary endpoint was confirmed objective response rate. The cORR was 38.1% in cohort A and 50.0% in cohort B. Median progression-free survival was 8.2 months in cohort A and 5.4 months in cohort B. Notably, 95.3% of previously treated patients had PD-L1 combined positive score < 10. No grade 4 or 5 treatment related adverse events occurred. Post-treatment TP53 mutation clearance and increased CD8⁺ T cell proportions predicted improved outcomes. The authors conclude that the combination of sitravatinib plus tislelizumab had promising efficacy and safety as chemo-free regimen for advanced TNBC, including tumors with low PD-L1 expression.