Open access Original research J Immunother Cancer: first published as 10.1136/jitc-2020-002191 on 19 March 2021. Downloaded from 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

Kuimin Mei,1 Shukui Qin,1 Zhendong Chen,2 Ying Liu,3 Linna Wang,4 Jianjun Zou4

To cite: Mei K, Qin S, Chen Z, ABSTRACT China is an area with a high PLC incidence, et al. Camrelizumab in Background Emerging clinical data suggest that contributing to >50% of the new cases and combination with apatinib in an immune in combination with deaths globally.1 2 Patients with PLC are often second-­line or above therapy for an antiangiogenic agent is a reasonable strategy for advanced primary liver cancer: diagnosed at the locally advanced stage or on multiple malignancies. We assessed the combination cohort A report in a multicenter developing distant metastasis, which is not of camrelizumab with apatinib in pretreated advanced phase Ib/II trial. Journal for suitable for surgery or other local treatment, primary liver cancer (PLC, cohort A) from a multicohort ImmunoTherapy of Cancer thereby leading to poor prognosis with a 2021;9:e002191. doi:10.1136/ phase Ib/II trial. 3 jitc-2020-002191 Methods Patients with PLC after prior systemic 5-year­ survival rate of only 10%–20%. treatment(s) were administered camrelizumab (3 mg/kg, Since the development of and ►► Additional material is once every 2 weeks) plus apatinib (125, 250, 375, or 500 systematic containing oxal- published online only. To view, mg; once per day) in a 3+3 dose-escala­ tion stage and iplatin in recent years, the progress of systemic please visit the journal online subsequent expansion stage. The primary endpoints were therapy for advanced PLC mainly came from (http://dx.​ ​doi.org/​ ​10.1136/​ ​jitc-​ tolerability and safety of study treatment. antiangiogenic molecular target drugs and 2020-002191).​ Results From April 2017 to July 2019, 28 patients (21 immune checkpoint inhibitors (ICIs).4 The with and 7 with intrahepatic median overall survival (mOS) for sorafenib, cholangiocarcinoma) received camrelizumab plus apatinib. KM and SQ are joint first , , , ramu- authors. Two dose-­limiting toxicities (both grade 3 diarrhea) were reported in the 500 mg cohort. Therefore, the 375 mg cirumab, and donafenib as first-line­ or http://jitc.bmj.com/ Accepted 14 February 2021 cohort was expanded. Of the 19 patients in the 375 mg second-­line therapy for advanced PLC is cohort, dose reduction to 250 mg occurred in 8 patients between 6.5 months and 13.6 months, and within 2 months after treatment initiation. Of the 28 most objective response rates (ORRs) are patients with PLC, 26 had grade ≥3 treatment-­related <10%.4–6 Compared with traditional molec- adverse events, with hypertension being the most ular target drugs and systemic chemotherapy, common (9/28). One treatment-­related death occurred. ICIs, represented by programmed death-1 The objective response rate was 10.7% (95% CI 2.3% (PD-1)/programmed death ligand-1 (PD-­L1) on September 28, 2021 by guest. Protected copyright. to 28.2%). Median progression-­free survival and overall inhibitors (such as and pembroli- survival were 3.7 months (95% CI 2.0 to 5.8) and 13.2 months (95% CI 8.9 to not reached), respectively. zumab), have significantly improved the effec- Conclusion The combination of camrelizumab with tiveness in the treatment of advanced PLC, 7 8 apatinib had a manageable toxicity and promising with the ORR being