Efficacy and safety of cadonilimab in recurrent/metastatic solid tumors including ICI-treated tumors in clinical practice: Cohorts of head and neck squamous cell carcinoma and cervical cancer.

e17502 Background: Checkpoint inhibitors (ICIs) has been approved for treating multiple solid tumors, the real-world clinical benefits are under widely discussion. In addition, as more patients failed previous ICIs, the following treatment strategies and effectiveness warrant investigation. Cadonilimab (AK104) is a PD-1/CTLA-4 bispecific antibody, which is expected to exert enhanced anti-tumor activity or reverse immunotherapy resistance after single target ICI. This study focused on the real-world efficacy and safety of cadonilimab in R/M solid tumors, first reported performance of cadonilimab in R/M head and neck squamous cell carcinoma (HNSCC), enriched performance of cadonilimab in R/M cervical cancer (CC), and also summarized the effectiveness of re-treatment with cadonilimab for patients failed previous ICIs. Methods: We reviewed histologically confirmed CC and HNSCC in our center. Those with R/M disease and received ≥ one cycle of cadonilimab were enrolled. Patients received cadonilimab (10mg/kg, Q3W) mono- or combination therapy. The primary endpoints were ORR and PFS (RECIST1.1). Secondary endpoints included DCR, OS, and AE (CTCAE 5.0). Results: As of December 15, 2024, a total of 36 patients (median age: 57 years) were enrolled, including 29 CC and 7 HNSCC patients. The median follow-up time was 12.1 months (9.9-14.3 months). Patients with CC were treated with cadonilimab monotherapy or combined with chemotherapy ± radiotherapy or ± anti-angiogenic therapies. The ORR were 100% (7/7), 60% (9/15), 28.6%(2/7) for 1 st , 2 nd and ≥ 3 rd line therapy, the mPFS were not reached, 6.2 months (95% CI[3.3 9.0] ), and 4.8 months (95% CI[0.3 9.4]), respectively. The mOS was not mature. Patients with HNSCC received cadonilimab plus anti-EGFR therapy (one 1 st line, five 2 nd line, one ≥3 rd line). The overall ORR, DCR and mPFS are 71.4% (5/7), 85.7% (6/7) and 8.0 months (95%CI[3.2-12.9]). The ORR and DCR of 2 nd line treatment were 80% (4/5), mPFS was 8.0 months (95CI[3.954-12.113]). mOS was not mature. Of the 11 patients who received cadonilimab for immunotherapy rechallenging, three achieved PR and six maintained SD, with ORR of 27.3% (3/11), DCR of 81.8%(9/11), and mPFS was 4.7 months (95%CI[0-10.3]). Of all patients, 19.4%(7/36) developed grade 3 AE(4 leukopenia, 1 anemia, 2 rash, and 1 pancreatitis). Conclusions: This real-world study first reported performance of cadonilimab (combined with anti-EGFR therapy) in R/M HNSCC, showing excellent ORR and PFS. In R/M CC, the combination regimen of cadonilimab based on clinical practice improved ORR (COMPASSION-16, ORR 82.9%; COMPASSION-03, ORR 32.3%). The overall safety is manageable. Furthermore, cadonilimab showed promising anti-tumor efficacy and potential to reverse resistance of single target ICI. Analysis with more samples and cancer types will continue.