Efficacy and safety of cadonilimab plus anti-EGFR monoclonal antibody as de-chemotherapy regimen in persistent, recurrent, or metastatic gynecologic cancer.

5538 Background: Cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, and Nimotuzumab, an anti-EGFR monoclonal antibody, have demonstrated effectiveness in treating persistent, recurrent, or metastatic (P/R/M) cervical cancer individually. However, the exploration of combined bi-specific immunotherapy and anti-EGFR target therapy remains unexplored in P/R/M gynecological cancer. Methods: This open-label, prospective single-arm phase II study (NCT05606263). Eligible participants were P/R/M gynecological cancer patients who declined or couldn’t tolerate chemotherapy, or had failed first-line or subsequent treatments, irrespective of PD-L1 status. Patients received Cadonilimab at 6 mg/kg plus Nimotuzumab at a dose of 400 mg every two weeks. The primary endpoint included safety and objective response rate (ORR), with secondary endpoints comprising progression-free survival (PFS) and overall survival (OS). Results: From July 2022 to February 2024, twenty-nine P/R/M gynecological cancer patients received at least one dose of cadonilimab plus Nimotuzumab, including 22 (75.9%) with cervical cancer, 4 (13.8%) with endometrial carcinoma, and 3 (10.3%) with vulva cancer. The median age was 60 years (range: 39–80 years). Reasons for participating in this clinical trial included refusal of chemotherapy (7/29), inability to tolerate chemotherapy (7/29), and failure of first-line or subsequent lines of systemic therapy (15/29). Among them, 5 patients progressed after PD-1/PD-L1 treatment. After a median follow-up of 6 months (range: 1–18), the best response was observed in 17 patients, with 3 achieving complete response (CR) and 14 partial response (PR). Notably 2 patients relapsed after PD-1 treatment. The ORR was 58.6% (95% CI, 39.7–77.7). Additionally 6 patients achieved stable disease (SD), while 6 patients experienced disease progression. The median PFS and OS were not reached, but the 6-month PFS rate was 58.1% (95% CI, 35.5–75.2), and the 6-month OS rate was 76.5% (95% CI, 54.6–88.8). Adverse events (AEs) were generally manageable and tolerable (Grade 1-2), including hypothyroidism (13.8%), immune-mediated hepatitis (13.8%), rash maculo-papular (6.9%), thrombocytopenia (6.9%) and nephritis (3.4%). Conclusions: To the best of our knowledge, this represents the inaugural clinical report on the de-chemotherapy regimen of Cadonilimab plus Nimotuzumab for P/R/M gynecological cancer. The combination exhibited a promising tumor response rate (58.6%), surpassing the 32.3% observed with Cadonilimab alone, and demonstrated a manageable safety profile. These findings suggest the potential of bi-specific immunotherapy coupled with anti-EGFR target therapy especially in patients who are resistant to chemotherapy or intolerant to it, even in cases where single- specific immunotherapy has previously failed. Clinical trial information: NCT05606263 .