Camrelizumab Combined with FOLFOX4 Regimen as First-Line Therapy for Advanced Hepatocellular Carcinomas: A Sub-Cohort of a Multicenter Phase Ib/II Study

Abstract

Background

Immune checkpoint inhibitors and chemotherapy can synergistically increase efficacy in a variety of malignancies. We conducted this phase Ib/II study to assess the safety and efficacy of anti-PD-1 antibody camrelizumab in combination with FOLFOX4 for treatment-naive advanced hepatocellular carcinoma (aHCC).

Methods

This open-label, multicenter phase Ib/II study (NCT03092895) enrolled patients with aHCC and without prior systemic treatment for treatment with camrelizumab (3 mg/kg) and FOLFOX4 every two weeks. First, six patients were enrolled, followed by an additional 28 patients after dose-limiting toxicity cases were determined to be <33% of patients. The primary endpoint was tolerability and safety of treatment.

Results

A total of 34 aHCC patients were enrolled and received study treatment. No dose-limiting toxicity were observed in the first six patients enrolled. Twenty-nine (85.3%) of the total 34 patients had grade ≥3 treatment-related adverse events (TRAEs), with the most common ones being decreased neutrophil count (55.9%) and decreased white blood cell count (38.2%). No TRAEs-related deaths occurred. The objective response and disease control rate were 29.4% (95% CI, 15.1–47.5) and 79.4% (95% CI, 62.1–91.3), respectively. The median duration of response, progression-free survival, and overall survival was 6.9 months (range, 3.3–11.5), 7.4 months (95% CI, 3.9–9.2), and 11.7 months (95% CI, 8.2–22.0), respectively.

Conclusion

Camrelizumab combined with FOLFOX4 for first-line treatment of patients with aHCC showed good safety and tolerability, with promising preliminary antitumor activity.

Keywords:

• PD-1 monoclonal antibody
• camrelizumab
• FOLFOX4 regimen
• hepatocellular carcinoma
• combination therapy

Acknowledgments

The sponsor of this study is Jiangsu Hengrui Medicine Co., Ltd. My heartfelt thanks to all the patients and their families, as well as to all the researchers and medical staff involved in this study. Medical writing for this manuscript was provided by Tengfei Zhang, PhD (Medical Writer at Hengrui) according to Good Publication Practice Guidelines.

This study was presented in part at the American Society of Clinical Oncology (ASCO) Annual Meeting as a poster presentation on June 03, 2019. The poster’s abstract was published in ‘Poster Abstracts’ in Journal of Clinical Oncology: https://ascopubs.org/doi/abs/10.1200/JCO.2019.37.15_suppl.4074.

Data Sharing Statement

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Ethics Approval and Consent to Participate

This study was conducted in strict compliance with Good Clinical Practice Guidelines, the Declaration of Helsinki, and the study protocol. The study protocol and amendments involved in this document were reviewed and approved by the Ethics Committees of each study site.

Consent for Publication

Not applicable.

Author Contributions

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

Disclosure

Xiao Zhang, Linna Wang, Xiaojing Zhang, and Jianjun Zou are employees of Jiangsu Hengrui Medicine Co., Ltd.

The authors declared no other conflicts of interest.

Additional information

Funding

This work was supported by Jiangsu Hengrui Medicine Co., Ltd.