Camrelizumab: an investigational agent for hepatocellular carcinoma

References

• Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209–249.
   PubMed Web of Science ®Google Scholar
• Shin SW, Ahn KS, Kim SW, et al. Liver resection versus local ablation therapies for hepatocellular carcinoma within the milan criteria: a systematic review and meta-analysis. Ann Surg. 2021;273(4):656–666.
   PubMed Web of Science ®Google Scholar
• Rizzo A. Tyrosine kinase inhibitors plus immune checkpoint inhibitors as neoadjuvant therapy for hepatocellular carcinoma: an emerging option? Expert Opin Investig Drugs. 2021;5:1–3.
   Google Scholar
• Bertuccio P, Turati F, Carioli G, et al. Global trends and predictions in hepatocellular carcinoma mortality. J Hepatol. 2017;67(2):302–309.
   PubMed Web of Science ®Google Scholar
• Han Y, Zhi WH, Xu F, et al. Selection of first-line systemic therapies for advanced hepatocellular carcinoma: a network meta-analysis of randomized controlled trials. World J Gastroenterol. 2021;27(19):2415.
   PubMed Web of Science ®Google Scholar
• Finn RS, Zhu AX, Farah W, et al. Therapies for advanced stage hepatocellular carcinoma with macrovascular invasion or metastatic disease: a systematic review and meta‐analysis. Hepatology. 2018;67(1):422–435.
   PubMed Web of Science ®Google Scholar
• Rizvi S, Wang J, El-Khoueiry AB. Liver Cancer Immunity. Hepatology. 2021;73 Suppl 1(Suppl 1):86–103.
   PubMedGoogle Scholar
• Ringelhan M, Pfister D, O’Connor T, et al. The immunology of hepatocellular carcinoma. Nat Immunol. 2018;19(3):222–232.
   PubMed Web of Science ®Google Scholar
• Doherty DG. Immunity, tolerance and autoimmunity in the liver: a comprehensive review. J Autoimmun. 2016;66:60–75.
   PubMed Web of Science ®Google Scholar
• Zongyi Y, Xiaowu L. Immunotherapy for hepatocellular carcinoma. Cancer Lett. 2020;470:8–17.
   PubMed Web of Science ®Google Scholar
• Zhong C, Li Y, Yang J, et al. Immunotherapy for hepatocellular carcinoma: current limits and prospects. Front Oncol. 2021;11:968.
   Web of Science ®Google Scholar
• Makarova-Rusher OV, Medina-Echeverz J, Duffy AG, et al. The yin and yang of evasion and immune activation in HCC. J Hepatol. 2015;62(6):1420–1429.
   PubMed Web of Science ®Google Scholar
• Chen DP, Ning WR, Jiang ZZ, et al. Glycolytic activation of peritumoral monocytes fosters immune privilege via the PFKFB3-PD-L1 axis in human hepatocellular carcinoma. J Hepatol. 2019;71(2):333–343.
   PubMed Web of Science ®Google Scholar
• Li Z, Li H, Zhao ZB, et al. SIRT4 silencing in tumor-associated macrophages promotes HCC development via PPARδ signalling-mediated alternative activation of macrophages. J Exp Clin Cancer Res. 2019;38(1):1–18.
   PubMed Web of Science ®Google Scholar
• Zhou D, Luan J, Huang C, et al. Tumor-associated macrophages in hepatocellular carcinoma: friend or foe? Gut Liver. 2021;15(4):500.
   PubMed Web of Science ®Google Scholar
• Kurebayashi Y, Ojima H, Tsujikawa H, et al. Landscape of immune microenvironment in hepatocellular carcinoma and its additional impact on histological and molecular classification. Hepatology. 2018;68(3):1025–1041.
   PubMed Web of Science ®Google Scholar
• Rizvi S, Wang J, El-Khoueiry AB. Liver Cancer Immunity. Hepatology. 2020;73(Suppl 1):86–103.
   PubMedGoogle Scholar
• Kim HD, Song GW, Park S, et al. Association between expression level of PD1 by tumor-infiltrating CD8+ T cells and features of hepatocellular carcinoma. Gastroenterology. 2018;155(6):1936–1950. e17.
   PubMed Web of Science ®Google Scholar
• Lindblad KE, Ruiz de Galarreta M, Lujambio A. Tumor-Intrinsic Mechanisms Regulating Immune Exclusion in Liver Cancers. Front Immunol. 2021;12:720.
   Web of Science ®Google Scholar
• Kudo M. Multistep human hepatocarcinogenesis: correlation of imaging with pathology. J Gastroenterol. 2009;44(19):112–118.
   PubMedGoogle Scholar
• Ghafar MTA, Morad MA, El-Zamarany EA, et al. Autologous dendritic cells pulsed with lysate from an allogeneic hepatic cancer cell line as a treatment for patients with advanced hepatocellular carcinoma: a pilot study. Int Immunopharmacol. 2020;82:106375.
   PubMed Web of Science ®Google Scholar
• Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382(20):1894–1905. IMbrave150.
   PubMed Web of Science ®Google Scholar
• Finn RS, Ryoo BY, Merle P, et al. Pembrolizumab as second-line therapy in patients with advanced hepatocellular carcinoma in KEYNOTE-240: a randomized, double-blind, phase III trial. J Clin Oncol. 2020;38(3):193–202.
   PubMed Web of Science ®Google Scholar
• El-Khoueiry AB, Sangro B, Yau T, et al. Nivolumab in patients with advanced hepatocellular carcinoma (CheckMate 040): an open-label, non-comparative, phase 1/2 dose escalation and expansion trial. Lancet. 2017;389(10088):2492–2502.
   PubMed Web of Science ®Google Scholar
• Kelley RK, Sangro B, Harris W, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J clin oncol. 2021;39(27):2991–3001.
   PubMed Web of Science ®Google Scholar
• Wu Q, Zhou W, Yin S, et al. Blocking triggering receptor expressed on myeloid cells‐1‐positive tumor‐associated macrophages induced by hypoxia reverses immunosuppression and anti‐programmed cell death ligand 1 resistance in liver cancer. Hepatology. 2019;70(1):198–214.
   PubMed Web of Science ®Google Scholar
• Hui E, Cheung J, Zhu J, et al. T cell costimulatory receptor CD28 is a primary target for PD-1–mediated inhibition. Science. 2017;355(6332):1428–1433.
   PubMed Web of Science ®Google Scholar
• West EE, Jin HT, Rasheed AU, et al. PD-L1 blockade synergizes with IL-2 therapy in reinvigorating exhausted T cells. J Clin Invest. 2013;123(6):2604–2615.
   PubMed Web of Science ®Google Scholar
• Amarnath S, Mangus CW, Wang JCM, et al. The PD-L1-PD-1 axis converts human TH1 cells into regulatory T cells. Sci Transl Med. 2011;3(111):111ra120–111ra120.
   PubMed Web of Science ®Google Scholar
• Mo H, Huang J, Xu J, et al. Safety, anti-tumour activity, and pharmacokinetics of fixed-dose SHR-1210, an anti-PD-1 antibody in advanced solid tumours: a dose-escalation, phase 1 study. Br J Cancer. 2018;119(5):538–545.
   PubMed Web of Science ®Google Scholar
• Jiangsu Hengrui Medicine. Camrelizumab achieve new breakthrough in immunotherapy of advanced liver cancer in China. [ Cited 2020 Mar 19]. Available from: https://www.hrs.com.cn/main_newshow/show-6340.html
   Google Scholar
• Zhu AX, Finn RS, Edeline J, et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224): a non-randomised, open-label phase 2 trial. Lancet Oncol. 2018;19(7):940–952.
   PubMed Web of Science ®Google Scholar
• Yau T, Park JW, Finn RS, et al. CheckMate 459: a randomized, multi-center phase III study of nivolumab (NIVO) vs sorafenib (SOR) as first-line (1L) treatment in patients (pts) with advanced hepatocellular carcinoma (aHCC). Ann Oncol. 2019;30:v874–v875.
   Web of Science ®Google Scholar
• Gu X, Gao XS, Xiong W, et al. Increased programmed death ligand-1 expression predicts poor prognosis in hepatocellular carcinoma patients. Onco Targets Ther. 2016;9:4805.
   PubMed Web of Science ®Google Scholar
• Herbst RS, Soria JC, Kowanetz M, et al. Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014;515(7528):563–567.
   PubMed Web of Science ®Google Scholar
• Finn RS, Ikeda M, Zhu AX, et al. Phase Ib study of lenvatinib plus pembrolizumab in patients with unresectable hepatocellular carcinoma. J Clin Oncol. 2020;38(26):2960–2970. (KEYNOTE-524).
   Web of Science ®Google Scholar
• Xu J, Shen J, Gu S, et al. Camrelizumab in combination with apatinib in patients with advanced hepatocellular carcinoma (RESCUE): a nonrandomized, open-label, phase II trial. Clin Cancer Res. 2021;27(4):1003–1011.
   PubMed Web of Science ®Google Scholar
• Kwon M, Jung H, Nam GH, et al. The right Timing, right combination, right sequence, and right delivery for Cancer immunotherapy. J Control Release. 2021;331:321–334.
   PubMed Web of Science ®Google Scholar
• Liu W, Zhang L, Xiu Z, et al. Combination of Immune Checkpoint Inhibitors with Chemotherapy in Lung Cancer. Onco Targets Ther. 2020;13:7229.
   PubMed Web of Science ®Google Scholar
• Qin S, Chen Z, Liu Y, et al. A phase II study of anti–PD-1 antibody camrelizumab plus FOLFOX4 or GEMOX systemic chemotherapy as first-line therapy for advanced hepatocellular carcinoma or biliary tract cancer. J clin oncol. 2019;37(15_suppl):4074.
   Web of Science ®Google Scholar
• Lickliter JD, Gan HK, Voskoboynik M, et al. A first-in-human dose finding study of camrelizumab in patients with advanced or metastatic cancer in Australia. Drug Des Devel Ther. 2020;14:1177.
   PubMed Web of Science ®Google Scholar
• Zhou C, Chen G, Huang Y, et al. Camrelizumab plus carboplatin and pemetrexed versus chemotherapy alone in chemotherapy-naive patients with advanced non-squamous non-small-cell lung cancer (CameL): a randomised, open-label, multicentre, phase 3 trial. Lancet Respir Med. 2021;9(3):305–314.
   PubMed Web of Science ®Google Scholar
• Huang J, Xu J, Chen Y, et al. Camrelizumab versus investigator’s choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020;21(6):832–842.
   PubMed Web of Science ®Google Scholar
• Lan C, Shen J, Wang Y, et al. Camrelizumab plus apatinib in patients with advanced cervical cancer (clap): a multicenter, open-label, single-arm, phase II trial. J clin oncol. 2020;38(34):4095–4106.
   PubMed Web of Science ®Google Scholar
• Fang W, Yang Y, Ma Y, et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018;19(10):1338–1350.
   PubMed Web of Science ®Google Scholar
• Xu J, Zhang Y, Jia R, et al. Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma, gastric, or esophagogastric junction cancer: an open-label, dose escalation and expansion study. Clin Cancer Res. 2019;25(2):515–523.
   PubMed Web of Science ®Google Scholar
• Qin S, Ren Z, Meng Z, et al. Camrelizumab in patients with previously treated advanced hepatocellular carcinoma: a multicentre, open-label, parallel-group, randomised, phase 2 trial. Lancet Oncol. 2020;21(4):571–580.
   PubMed Web of Science ®Google Scholar
• Lee HT, Lee SH, Heo YS. Molecular interactions of antibody drugs targeting PD-1, PD-L1, and CTLA-4 in immuno-oncology. Molecules. 2019;24(6):1190.
   PubMed Web of Science ®Google Scholar
• Miao L, Zhang Z, Ren Z, et al. Application of Immunotherapy in Hepatocellular Carcinoma. Front Oncol. 2021;11:1–15.•• Comprehensive review discussing the application and research progress of immunotherapy in the treatment of hepatocellular carcinoma.
   Web of Science ®Google Scholar
• Desai J, Deva S, Lee JS, et al. Phase IA/IB study of single-agent tislelizumab, an investigational anti-PD-1 antibody, in solid tumors. J Immunother Cancer. 2020;8(1):1–10.
   Web of Science ®Google Scholar
• Lickliter JD, Gan HK, Voskoboynik M, et al. A first-in-human dose finding study of camrelizumab in patients with advanced or metastatic cancer in Australia. Drug Des Devel Ther. 2020;14:1177–1189.
   PubMed Web of Science ®Google Scholar
• Patnaik A, Kang SP, Rasco D, et al. Phase I study of pembrolizumab (MK-3475; anti–PD-1 monoclonal antibody) in patients with advanced solid tumors. Clin Cancer Res. 2015;21(19):4286–4293.
   PubMed Web of Science ®Google Scholar
• Wang C, Thudium KB, Han M, et al. In vitro characterization of the anti-PD-1 antibody nivolumab, BMS-936558, and in vivo toxicology in non-human primates. Cancer Immunol Res. 2014;2(9):846–856.
   PubMed Web of Science ®Google Scholar
• Fu J, Wang F, Dong L, et al. Preclinical evaluation of the efficacy, pharmacokinetics and immunogenicity of JS-001, a programmed cell death protein-1 (PD-1) monoclonal antibody. Acta Pharmacol Sin. 2017;38(5):710–718.
   PubMed Web of Science ®Google Scholar
• Zhang S, Zhang M, Wu W, et al. Preclinical characterization of Sintilimab, a fully human anti-PD-1 therapeutic monoclonal antibody for cancer. Antibody Therapeutics. 2018;1(2):65–73.
   PubMedGoogle Scholar
• Sangro B, Chan SL, Meyer T, et al. Diagnosis and management of toxicities of immune checkpoint inhibitors in hepatocellular carcinoma. J Hepatol. 2020;72(2):320–341.
   PubMed Web of Science ®Google Scholar
• Ren Z, Qin S, Meng Z, et al. A Phase 2 Study of Camrelizumab for Advanced Hepatocellular Carcinoma: two-Year Outcomes and Continued Treatment beyond First RECIST-Defined Progression. Liver Cancer. 2021;10(4):375–384.
   Google Scholar
• Yang X, Sun H, Hu B, et al. 944P Adjuvant camrelizumab combined with apatinib treatment after resection of hepatocellular carcinoma in CNLC II and III stage: a single-center prospective phase II trial. Ann Oncol. 2021;32:S824.
   Web of Science ®Google Scholar
• Pfister D, Núñez NG, Pinyol R, et al. NASH limits anti-tumour surveillance in immunotherapy-treated HCC. Nature. 2021;592(7854):450–456.
   PubMed Web of Science ®Google Scholar
• Haber PK, Puigvehí M, Castet F, et al. Evidence-based management of HCC: systematic review and meta-analysis of randomized controlled trials (2002-2020). Gastroenterology. 2021;3(161):879–898.
   Google Scholar
• Zhu AX, Kang YK, Yen CJ, et al. Ramucirumab after sorafenib in patients with advanced hepatocellular carcinoma and increased α-fetoprotein concentrations (REACH-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(2):282–296.
   PubMed Web of Science ®Google Scholar
• Ma LJ, Feng FL, Dong LQ, et al. Clinical significance of PD-1/PD-Ls gene amplification and overexpression in patients with hepatocellular carcinoma. Theranostics. 2018;8(20):5690.
   PubMed Web of Science ®Google Scholar
• Elhendawy M, Abdul-Baki EA, Abd-Elsalam S, et al. MicroRNA signature in hepatocellular carcinoma patients: identification of potential markers. Mol Biol Rep. 2020;47(7):4945–4953.
   PubMed Web of Science ®Google Scholar
• El-Gebaly F, Abou-Saif S, Elkadeem M, et al. Study of serum soluble programmed death ligand 1 as a prognostic factor in hepatocellular carcinoma in Egyptian patients. Curr Cancer Drug Targets. 2019;19(11):896–905.
   PubMed Web of Science ®Google Scholar
• Watany M, Badawi R, Elkhalawany W, et al. Study of Dickkopf-1 (DKK-1) gene expression in hepatocellular carcinoma patients. J Clin Diagn Res. 2017;11(2):OC32.
   PubMed Web of Science ®Google Scholar
• Shen Q, Fan J, Yang XR, et al. Serum DKK1 as a protein biomarker for the diagnosis of hepatocellular carcinoma: a large-scale, multicentre study[J]. Lancet Oncol. 2012;13(8):817–826.
   PubMed Web of Science ®Google Scholar
• Yavuz BG, Hasanov E, Lee SS, et al. Current Landscape and Future Directions of Biomarkers for Immunotherapy in Hepatocellular Carcinoma. J Hepatocell Carcinoma. 2021;8:1195.
   PubMed Web of Science ®Google Scholar
• Markham A, Keam SJ. Camrelizumab: first global approval. Drugs. 2019;79(12):1355–1361.
   PubMed Web of Science ®Google Scholar
• Chen Z, Lu X, Koral K. The clinical application of camrelizumab on advanced hepatocellular carcinoma. Expert Rev Gastroenterol Hepatol. 2020;14(11):1017–1024.
   PubMed Web of Science ®Google Scholar