Serum Concentration of CD137 and Tumor Infiltration by M1 Macrophages Predict the Response to Sintilimab plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma Patients

Author:

Zhang Wen1,Gong Caifeng1ORCID,Peng Xuenan1,Bi Xinyu2,Sun Yongkun1ORCID,Zhou Jianguo2,Wu Fan2,Zeng Huiying3,Wang Yan4,Zhou Hui4,Zhao Hong2,Cai Jianqiang2,Zhou Aiping1ORCID

Affiliation:

1. 1Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

2. 2Department of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

3. 3Department of Interventional Therapy, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

4. 4Innovent Biologics, Suzhou, China.

Abstract

Abstract Purpose: This study aimed to investigate the biomarkers of sintilimab (anti–PD-1) plus IBI305 (a bevacizumab biosimilar) in advanced hepatocellular carcinoma (HCC), as well as their safety and efficacy. Patients and Methods: A total of 50 patients with advanced HCC received sintilimab (200 mg) plus IBI305 (7.5 or 15 mg/kg), treated every 3 weeks in a phase Ib clinical study. We performed baseline serum cytokine analysis using bead-based multiplex immunoassay and multiplex immunofluorescence on tissue specimens to discover novel biomarkers of response to VEGF/PD-1 combination therapy in HCC. Results: The overall response rate was 34.0% (17/50). The median progression-free survival (PFS) and the median overall survival were 10.5 and 20.2 months, respectively. The incidence of grade 3 to 5 adverse events was lower in the 7.5 mg/kg (13.8%) than in the 15 mg/kg (28.6%) dose groups. Biomarker analysis showed that the serum CD137 concentration was significantly higher in patients with clinical benefit (CB) than in those without CB (median, 32.8 pg/mL vs. 19.8 pg/mL, P = 0.034). A markedly longer PFS was observed in patients with high CD137 concentrations compared with those with low concentrations (median, 14.2 months vs. 4.1 months, P = 0.001). The higher density of M1 macrophages (CD68+CD163–) in the stroma was also associated with higher efficacy (P = 0.033) and a longer PFS (P = 0.024). Conclusions: Sintilimab plus IBI305 was well tolerated and was effective therapy for advanced HCC. Both serum concentrations of CD137 and tumor infiltration of M1 macrophages may serve as potential predictive biomarkers. See related commentary by Cappuyns and Llovet, p. 3405

Funder

Non-profit Central Research Institution Fund of Chinese Academy of Medical Sciences

Publisher

American Association for Cancer Research (AACR)

Subject

Cancer Research,Oncology

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