Camrelizumab in combination with apatinib in second-line or above therapy for advanced primary liver cancer: cohort A report in a multicenter phase Ib/II trial

Abstract

Background: Emerging clinical data suggest that an immune checkpoint inhibitor in combination with an antiangiogenic agent is a reasonable strategy for multiple malignancies. We assessed the combination of camrelizumab with apatinib in pretreated advanced primary liver cancer (PLC, cohort A) from a multicohort phase Ib/II trial.

Methods: Patients with PLC after prior systemic treatment(s) were administered camrelizumab (3 mg/kg, once every 2 weeks) plus apatinib (125, 250, 375, or 500 mg; once per day) in a 3+3 dose-escalation stage and subsequent expansion stage. The primary endpoints were tolerability and safety of study treatment.

Results: From April 2017 to July 2019, 28 patients (21 with hepatocellular carcinoma and 7 with intrahepatic cholangiocarcinoma) received camrelizumab plus apatinib. Two dose-limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cohort was expanded. Of the 19 patients in the 375 mg cohort, dose reduction to 250 mg occurred in 8 patients within 2 months after treatment initiation. Of the 28 patients with PLC, 26 had grade ≥3 treatment-related adverse events, with hypertension being the most common (9/28). One treatment-related death occurred. The objective response rate was 10.7% (95% CI 2.3% to 28.2%). Median progression-free survival and overall survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively.

Conclusion: The combination of camrelizumab with apatinib had a manageable toxicity and promising antitumor activity in patients with advanced PLC. Apatinib at a dose of 250 mg is recommended as a combination therapy for further studies of advanced PLC treatment.

Trial registration numbers: NCT03092895.

Keywords: combination; drug therapy; immunotherapy; liver neoplasms.

Conflict of interest statement

Competing interests: LW and JZ are employees of Jiangsu Hengrui Medicine Co., Ltd.

© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1

Trial profiles.

Figure 2

Treatment interruption and dose reduction of apatinib in the 375 mg group. Apatinib administration was interrupted in all 19 patients due to adverse events but was never resumed in two patients as the prespecified criteria for treatment resumption were not met, and the two patients progressed before the cut-off date. The 5 patients with intrahepatic cholangiocarcinoma were labeled with asterisks (*), and the other 14 patients with hepatocellular carcinoma were unlabeled.

Figure 3

Best percentage changes from baseline in terms of the target lesion sizes. The red stars represent the patients with confirmed partial response. The seven patients with intrahepatic cholangiocarcinoma were labeled with asterisks (*), and the other 21 patients had hepatocellular carcinoma.

Figure 4

(A) OS and (B) PFS. HCC, hepatocellular carcinoma; ICC, intrahepatic cholangiocarcinoma; NR, not reached; OS, overall survival; PFS, progression-free survival.