Innovent Biologics, Inc and Eli Lilly have jointly announced the final clinical outcome and biomarker analysis of the open-label, phase-Ib study (NCT04072679 of Sintilimab plus Bevacizumab biosimilar injection for advanced hepatocellular carcinoma at the 2022 ASCO Gastrointestinal Cancers Symposium, Innovent Biologics informed via a statement.

The statement also said that the study, which was conducted in China, evaluated the treatment of Sintilimab plus Bevacizumab biosimilar injection for patients with local advanced or metastatic HCC with or without previous systemic treatment or systemic treatment failure. The phase-Ib study included dose escalation and dose-expansion stages. In the dose-escalation stage, patients were randomly assigned to receive Sintilimab 200mg plus Bevacizumab biosimilar 7.5 mg/kg (low-dose group) or 15 mg/kg (high-dose group). In the dose-expansion stage safety and efficacy were assessed for each dose group. A total of fifty patients were enrolled in final analysis, with 29 patients administered Bevacizumab biosimilar 7.5 mg/kg and 21 patients 15 mg/kg. The safety profile was consistent with that observed in previously reported studies of Sintilimab and Bevacizumab biosimilar, without new or unexpected safety signals. The most common treatment-related adverse events (TRAE) were hypertension (32 per cent), proteinuria (26 per cent) and fever (26 per cent). The incidence of grade ≥ 3 adverse events in the high-dose group was 28.6 per cent, while 13.8 per cent in the low-dose group.

The Overall Response Rate (ORR) was 34 per cent (17/50) and ORRs for the low-dose and high-dose groups were 31 per cent and 38 per cent, respectively. The Disease Control Rate (DCR) was 78 per cent (39/50). Median progression-free survival (PFS) was 10.5 months (95%CI, 8.4-12.7) and median overall survival (OS) was 20.2 months (95%CI, 16.1 -24.3). Further, biomarker analysis showed that patients with a high level of CD137 ≥ 31.8 pg/mL have longer PFS (mPFS:14.2 vs. 4.1months, p=0.001) and OS (mOS: NR vs.15.6months, p=0.023). In addition, the Tumor immune Microenvironment (TiME）analysis demonstrated that the high density of M1 macrophages (CD68+, CD163-) in stroma was related to higher efficacy (p=0.033), longer PFS (p=0. 024) and OS (p =0.046), the statement further mentioned.

Professor Zhou Aiping from the Cancer Hospital of the Chinese Academy of Medical Sciences stated, “This study not only showed the safety and efficacy data for Sintilimab in combination with different doses of bevacizumab, but also identified biomarkers that could predict the efficacy of the combined treatment regimen for hepatocellular carcinoma, which lays the groundwork for more individualised treatment.”

In addition, Dr Zhou Hui, Senior Vice President, Innovent Biologics, said, “Sintilimab plus Bevacizumab biosimilar was approved for advanced hepatocellular carcinoma by National Medical Products Administration (NMPA) and successfully included in the National Reimbursement Drug List (NRDL) in 2021. This study showed the clinical data of Sintilimab in combination with two different doses of Bevacizumab biosimilar, potentially offering more treatment options for physicians. Meanwhile, the exploration of biomarkers for predicting hepatocellular carcinoma immunotherapy will contribute to better treatment options and represent a step towards precise and individualised treatment.”