In a Chinese phase 1b/II trial (COMPASSION-03) reported in The Lancet Oncology, Gao et al found that the anti–PD-1/CTLA-4 bispecific antibody cadonilimab showed activity in previously treated patients with a range of advanced solid tumors, including advanced cervical cancer, esophageal squamous cell carcinoma, and hepatocellular carcinoma.

Study Details

In the multicenter trial, 240 patients with unresectable advanced solid tumors—who had received at least one prior systemic therapy and had received no prior anti–PD-1, anti–PD-L1, or anti–CTLA-4 treatment—were enrolled between January 2019 and January 2021. A total of 83 patients received cadonilimab at 6 mg/kg and 10 mg/kg every 2 weeks in the dose-escalation phase, and at 6 mg/kg and a fixed dose of 450 mg every 2 weeks in the dose-expansion phase. In phase II, a total of 157 patients received cadonilimab at 6 mg/kg every 2 weeks, including 111 with cervical cancer, 22 with esophageal squamous cell carcinoma, and 24 with hepatocellular carcinoma. The primary efficacy outcome was objective response rate in phase II.

Responses

No dose-limiting toxicities were observed in the dose-escalation phase. 

At a median follow-up of 14.6 months (interquartile range [IQR] = 13.1–17.5 months) in the cervical cancer cohort, objective responses were observed in 32 (32.3%, 95% confidence interval [CI] = 23.3%–42.5%) of 99 evaluable patients, including complete response in 14 (14%). Median duration of response was not reached (95% CI = 7.4 months to not evaluable). The disease control rate was 51.5%.

At a median follow-up of 17.9 months (IQR = 4.0–15.1 months) in the esophageal squamous cell carcinoma cohort, objective responses (all partial) were observed in 4 (18.2%, 95% CI = 5.2%–40.3%) of 22 evaluable patients. Median response duration was 10.2 months (95% CI = 7.5 months to not evaluable). The disease control rate was 50.0%.

At a median follow-up of 19.6 months (IQR = 8.7–19.8 months) in the hepatocellular carcinoma cohort, objective responses (all partial) were observed in 4 (16.7%, 95% CI = 4.7%–37.4%) of 24 evaluable patients. Median response duration was not reached (95% CI = 3.6 months to not evaluable). The disease control rate was 62.5%.

Overall, the objective response rate among 89 patients with a PD-L1 combined positive score < 1 was 16.7%.

Adverse Events

Among all 240 patients, grade 3 or 4 treatment-related adverse events occurred in 67 (28%), most commonly anemia (3%), increased lipase (2%), decreased appetite (2%), decreased body weight (1%), decreased neutrophil count (1%), and infusion-related reaction (1%). Serious treatment-related adverse events occurred in 23% of patients, most commonly abnormal hepatic function (2%) and immune-mediated myocarditis (1%).

Treatment-related adverse events led to discontinuation of treatment in 7%. Immune-mediated adverse events occurred in 51% of patients and were grade ≥ 3 in 14%. Treatment-related adverse events led to death in five patients, due to myocardial infarction in one and unknown cause in four.

The investigators concluded, “Cadonilimab showed an encouraging tumor response rate, with a manageable safety profile, suggesting the potential of cadonilimab for the treatment of advanced solid tumors.”

Jiafu Ji, MD, of the Gastrointestinal Cancer Center, Peking University Cancer Hospital & Institute, and Xiaohua Wu, MD, of Fudan University Shanghai Cancer Center, Shanghai, are the corresponding authors for The Lancet Oncology article.

Disclosure: The study was funded by Akeso Biopharma. For full disclosures of the study authors, visit thelancet.com.