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.
Cancer
Care/Management

Authors

Zhang Zhang, Fei Fei, Lao Lao, Liu Liu, Zhu Zhu, Zhai Zhai, Huang Huang, Deng Deng, Wang Wang, Fang Fang, Zhang Zhang, Xu Xu, Lu Lu, Zhu Zhu, Zhou Zhou
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