Neoadjuvant tislelizumab (anti-PD-1 antibody) plus chemotherapy in patients with advanced epithelial ovarian cancer: the exploratory NAIVE trial.

The clinical efficacy and immune modulation of neoadjuvant immunochemotherapy for epithelial ovarian cancer (EOC) remain uncertain. To clarify these effects, the NAIVE trial (NCT04815408), a prospective phase II study, evaluated the efficacy of neoadjuvant platinum-based chemotherapy with tislelizumab (NACI) in comparison with chemotherapy alone (NAC) in patients with FIGO IIIC-IV EOC. The primary endpoint was the 1-year progression-free survival (PFS) rate; the secondary endpoints included PFS, R0 resection, clinical and pathological responses, and safety. Between April 2021 and July 2024, 25 patients were included in the final analysis. After a median follow-up period of 30.7 months, NACI was associated with numerically prolonged progression-free survival (27.2 vs. 21.8 months; HR = 0.44, 95% CI 0.15-1.26; P = 0.127), with higher 1-year (92.3% vs. 83.3%) and 2-year (62.3% vs. 31.8%) PFS rates than NAC. NACI also yielded superior tumor responses, including higher ORR (69.2% vs. 58.3%), more R0 resections, and increased CRS3 rates. No unexpected safety signals emerged, and immune-related adverse events were manageable. Immune profiling techniques, such as single-cell RNA sequencing and CyTOF, identified distinct signatures. NACI responders demonstrated heightened CD8+ T-cell-mediated toxicity and metabolic fitness, whereas nonresponders exhibited exhaustion phenotypes. Furthermore, the response correlated with enrichment of the CXCL13+Th1-GC B-cell-tertiary lymphoid structure (TLS) axis, accompanied by increased TLS activity and differentiation to IgG-producing plasma cells. Overall, NACI yielded PFS trends with acceptable safety, but without statistical significance. The mechanistic analyses highlight the role of the CXCL13+Th1-GC B-cell-TLS axis as a potential biomarker and driver of therapeutic response.