Efficacy and safety of cadonilimab (CD) in combination with disitamab vedotin (RC48) or nab-paclitaxel (NP) in the treatment of recurrent or metastatic cervical cancer (r/mCC): A prospective, double-cohort, multicenter, open-label, phase II clinical study.

5526 Background: The prognosis for patients(pts) with r/mCC is poor. The available second-line treatment regimens are limited, highlighting the need for more effective therapies. CD is a dual-target immune checkpoint inhibitor targeting PD-1 and CTLA-4 and RC48 is an antibody-drug conjugate targeting HER2. Here, we report updated results from a phase II study of CD plus RC48 or NP in r/mCC. Methods: This is a prospective, multicenter, open-label, phase II trial with two parallel cohorts(AK001). Eligible patients had r/mCC with progression after 1-3 prior lines of chemotherapy. Patients were assigned by HER2 immunohistochemistry (IHC): cohort I (HER2 IHC 1+ - 3+) received CD (6mg/kg) plus RC48 (2.5mg/kg) biweekly; cohort II (HER2 IHC 0) received CD (10mg/kg) plus NP (260mg/m 2 ) triweekly. The primary endpoint of the study was objective response rate (ORR). Key secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS) and safety. A Simon's two-stage design was applied, with the ORR from the innovaTV 204 study as a historical control, which was 24%. Assuming the ORR for cohort I is 50% and for cohort II is 40%, with a power of 0.8 and a one-sided α of 0.05, and considering a dropout rate of 10%, the total sample size calculated was 32 for cohort I and 42 for cohort II. Results: As of the data cutoff (January 15, 2026), 62 pts were enrolled, including 53 evaluable pts (26 in cohort I and 27 in cohort II) across 5 large academic centers in China. Median follow-up was 12.03 months (range, 1.87 - 26.57). For cohort I, the ORR was 57.7% ( 95% CI, 36.9% - 76.6%) and median DOR was not reached (95% CI, 3.97 - NR). Median PFS was 8.23 (95% CI, 3.41 - 13.06) months and 12-month PFS rate was 45%. For cohort II, the ORR was 55.6% ( 95% CI, 35.3% - 74.5%) and median DOR was 4.57 (95% CI, 2.30 - 6.83) months. Median PFS was 5.87 (95% CI, 4.55 - 7.19) months and 12-month PFS rate was 38%. Toxicity was tolerable in both cohorts. Grade 3-4 treatment-related adverse events occurred in 15.4% of pts in cohort I and 21.4% of pts in cohort II. Conclusions: Our current results support a potential HER2 expression-guided option for second-line treatment of r/mCC. CD plus RC48 demonstrated favorable efficacy and a manageable safety profile, and may emerge as a novel effective combination for the treatment of HER2 positive cervical cancer. Long-term benefits and further analysis of the role of this combination therapy in r/mCC will be critical to advancing treatment strategies. Clinical trial information: ChiCTR2300076740. Antitumor activity assessed by RECIST version 1.1. Cohort I (n=26) Cohort II (n=27) ORR 15(57.7%) 15(55.6%) 95%CI 36.9 - 76.6 35.3 - 74.5 DCR 24(92.3%) 20(74.1%) 95%CI 74.9 - 99.1 53.7 - 88.9 Best Overall Response CR 3(11.5%) 0 PR 12(46.2%) 15(55.6%) SD 9(34.6%) 5(18.5%) PD 2(7.7%) 7(25.9%)