Introduction: Gynecologic clear cell carcinoma (CCC) is an uncommon histologic entity for which therapeutic options remain limited, and the clinical activity of immune checkpoint inhibitor (ICI)-based treatment has not been clearly defined.

Objective: To synthesize the available evidence on efficacy and safety of ICI-containing regimens in gynecologic CCC.

Methods: We performed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses 2020-guided systematic review and meta-analysis. PubMed, Web of Science, and Embase were searched for peer-reviewed full-text studies published between January 2016 and February 7, 2026 that investigated ICI-based treatment in gynecologic CCC. Studies were eligible if they included objective response rate (ORR), grade ≥ 3 adverse events (AEs), or both. Pooled proportions were obtained through a binomial random-intercept generalized linear mixed model (GLMM); subgroup and sensitivity analyses were exploratory.

Results: Six studies included 181 patients in the efficacy analysis and 189 in the safety analysis. The GLMM estimate for ORR was 0.31 (95% confidence interval [CI], 0.20–0.44; I² = 66.1%), and the 95% prediction interval was 0.06–0.74. By treatment strategy, exploratory pooled ORRs were 0.17 (95% CI: 0.07–0.39) for ICI monotherapy and 0.42 (95% CI: 0.32–0.52) for combination regimens. The conventional subgroup comparison yielded p = 0.040, whereas Knapp–Hartung-adjusted meta-regression yielded p=0.094. For study-defined grade ≥ 3 AEs, the pooled proportion was 0.24 (95% CI: 0.12–0.40; I²=78.1%) with a 95% prediction interval of 0.02–0.81. Corresponding exploratory safety estimates were 0.31 for combination therapy and 0.15 for monotherapy (p_between = 0.160).

Conclusion: ICI-containing therapy shows variable antitumor activity across gynecologic CCC cohorts. Combination cohorts had numerically higher response and severe-toxicity rates, but these nonrandomized across-study contrasts were sensitive to small-sample adjustment and confounded by differences in regimens and populations. Overall certainty of the evidence was very low.