Efficacy and safety of cadonilimab, an anti-PD-1/CTLA4 bi-specific antibody, in previously treated recurrent or metastatic (R/M) cervical cancer: a multicenter, open-label, single-arm, phase II trial (075)

Objectives: No standard of care in the 2L+ setting for women with recurrent or metastatic (R/M) cervical cancer. Cadonilimab (AK104) is a bi-specific antibody against PD-1 and CTLA4. We assessed the efficacy and safety of cadonilimab in immune checkpoint inhibitor (ICI) naïve patients (pts) with R/M cervical cancer, regardless of PD-L1 status. Methods: This multi-center, open-label, single-arm, phase II study enrolled pts with advanced cervical cancer who had progressed on or after two or fewer previous doublet chemotherapy with or without bevacizumab. Pts received cadonilimab 6 mg/kg every two weeks. The primary endpoint was ORR assessed by the independent radiological review committee (IRRC) per RECIST version 1.1, and the key secondary endpoint was the duration of response (DoR). Results: As of August 5, 2021, 111 pts had received at least one dose of cadonilimab. The median age was 52.0 years (range: 27-73 years). Thirty-six percent of pts had received two prior lines of systemic therapy, 92.8% had squamous cell disease, 56.8% had an ECOG score of 1, 25.0% had received bevacizumab. After median follow-up of 9.63 months (mo) (range: 0.7-21.4), the IRRC-assessed confirmed ORR in 100 pts evaluable for efficacy was 33.0% (95% CI: 23.9%-43.1%), with 12 (12.0%) CR and 21 (21.0%) PR. Median DoR was not reached (range: 0.95+-13.14+ mo); 6- and 12-mo DoR rates were 77.6% and 52.9%, respectively. Median PFS was 3.75 mo (95% CI: 2.00-6.41); 6-and 12 - mo PFS rates were 41.4% and 21.2%, respectively. Median OS was 17.51 mo (95% CI: 11.37 - NE); 6- and 12 - mo OS rates were 80.1% and 64.6%, respectively. Among 64 pts with PD-L1 positive tumors (CPS≥1), the ORR was 43.8% (95% CI: 31.4%-56.7%), the median PFS was 6.34 mo (95% CI: 3.12-11.17), and the median OS was not reached (95% CI: 17.51 mo-NE). Treatment-related adverse events (TRAEs) occurred in 96.4% of 111 patients. Grade 3 to 4 treatment-related adverse events occurred in 28.8% of 111 patients; the most common were anemia (7.2%) and decreased appetite (2.7%). Conclusions: Cadonilimab monotherapy is efficacious and safe as 2L+ treatment of R/M cervical cancer in ICI naïve pts, regardless of PD-L1 status. A phase III confirmatory trial to evaluate cadonilimab plus chemotherapy as 1L treatment for R/M cervical cancer is ongoing. Objectives: No standard of care in the 2L+ setting for women with recurrent or metastatic (R/M) cervical cancer. Cadonilimab (AK104) is a bi-specific antibody against PD-1 and CTLA4. We assessed the efficacy and safety of cadonilimab in immune checkpoint inhibitor (ICI) naïve patients (pts) with R/M cervical cancer, regardless of PD-L1 status. Methods: This multi-center, open-label, single-arm, phase II study enrolled pts with advanced cervical cancer who had progressed on or after two or fewer previous doublet chemotherapy with or without bevacizumab. Pts received cadonilimab 6 mg/kg every two weeks. The primary endpoint was ORR assessed by the independent radiological review committee (IRRC) per RECIST version 1.1, and the key secondary endpoint was the duration of response (DoR). Results: As of August 5, 2021, 111 pts had received at least one dose of cadonilimab. The median age was 52.0 years (range: 27-73 years). Thirty-six percent of pts had received two prior lines of systemic therapy, 92.8% had squamous cell disease, 56.8% had an ECOG score of 1, 25.0% had received bevacizumab. After median follow-up of 9.63 months (mo) (range: 0.7-21.4), the IRRC-assessed confirmed ORR in 100 pts evaluable for efficacy was 33.0% (95% CI: 23.9%-43.1%), with 12 (12.0%) CR and 21 (21.0%) PR. Median DoR was not reached (range: 0.95+-13.14+ mo); 6- and 12-mo DoR rates were 77.6% and 52.9%, respectively. Median PFS was 3.75 mo (95% CI: 2.00-6.41); 6-and 12 - mo PFS rates were 41.4% and 21.2%, respectively. Median OS was 17.51 mo (95% CI: 11.37 - NE); 6- and 12 - mo OS rates were 80.1% and 64.6%, respectively. Among 64 pts with PD-L1 positive tumors (CPS≥1), the ORR was 43.8% (95% CI: 31.4%-56.7%), the median PFS was 6.34 mo (95% CI: 3.12-11.17), and the median OS was not reached (95% CI: 17.51 mo-NE). Treatment-related adverse events (TRAEs) occurred in 96.4% of 111 patients. Grade 3 to 4 treatment-related adverse events occurred in 28.8% of 111 patients; the most common were anemia (7.2%) and decreased appetite (2.7%). Conclusions: Cadonilimab monotherapy is efficacious and safe as 2L+ treatment of R/M cervical cancer in ICI naïve pts, regardless of PD-L1 status. A phase III confirmatory trial to evaluate cadonilimab plus chemotherapy as 1L treatment for R/M cervical cancer is ongoing.