Study design and patients
DLTs, HCC, BCLC
LIVER DISEASE, ONCOLOGY
This study was a multicenter, open-label, single-arm, phase Ib/II clinical trial of cadonilimab plus lenvatinib in patients with aHCC. This trial was conducted across nine centers in China. There are two cohorts in this study. Three patients in cohort A received cadonilimab (C) 6 mg/kg intravenously on day 1, every 2 weeks (Q2W) plus lenvatinib (L) 8 mg (if body weight <60 kg) or 12 mg (if body weight ≥60 kg) orally once daily; if no DLTs were reported within 28 days after first dose, then subjects were further enrolled to 30. Three patients in cohort B received cadonilimab 15 mg/kg intravenously on day 1, every 3 weeks (Q3W), along with lenvatinib 8 mg (if body weight <60 kg) or 12 mg (if body weight ≥60 kg) orally once daily. If no DLTs were reported within 21 days of first dose, then enrollment could be continued to 30. An additional three subjects were required if one(1/3) of the first three subjects in either group displayed DLT. If ≥2 patients experienced DLTs in a total of six subjects, the sponsor and investigator will discuss and consider whether to continue, modify, or discontinue the study. The dosage group was determined based on the phase Ia dose escalation study from Australia and phase I/II clinical trial in China.Eligible patients (≥18 years and ≤75 years) had a histologically confirmed HCC or clinically unresectable confirmed HCC according to American Association for the Study of Liver Diseases (AASLD) criteria, were classified as stage B or C by Barcelona Clinic Liver Cancer (BCLC) criteria, or ineligible for surgery or locoregional therapy for patients with BCLC stage B or progressed after surgery or locoregional therapy and not receiving previous systemic therapy, had at least one measurable target lesion (per RECIST v1.1), and had a Child-Pugh Score class A and Eastern Cooperative Oncology Group performance status of 0–1.The trial was conducted in accordance with the International Conference on Harmonization guidelines for Good Clinical Practice and the Declaration of Helsinki. The institutional review board or independent ethics committee at Chinese People’s Liberation Army (PLA) General Hospital and other eight centers approved this trial.