Innovent and Eli Lilly Announce Final Results of Phase Ib Study of Sintilimab Plus Bevacizumab Biosimilar in Advanced Hepatocellular Carcinoma with ORR of 34% and DCR of 78%
Jan 23, 2022 01:33
CST Updated
01:33
Innovent
High-end Biologics Developer
Eli Lilly
Global Pharmaceutical R&D and Production Company
News on January 22, 2022 /BioValleyBIOON/ -- Innovent Bio (Innovent Biologics) andEli Lilly(Eli Lilly) recently at the 2022 American Society of Clinical Oncology GastrointestinalTumorAnnounced at the ASCO GI SymposiumPD-1 Inhibitor Tyvyt® (generic name: sintilimab, Sintilimab Injection) in combination with VEGF-targeted drug Byvasda® (generic name: bevacizumab, Bevacizumab Biosimilar)Final Clinical Results of the Open-Label Phase Ib Study (NCT04072679) for the Treatment of Advanced Hepatocellular Carcinoma (HCC)BiomarkerAnalysis.
The study was conducted in China, enrolling patients with locally advanced or metastatic RCC who had not received systemic treatment or had failed systemic treatment. It is evaluating the combination regimen of Tyvyt and Byvasda. The study includes a dose-escalation phase and a dose-expansion phase. In the dose-escalation phase, patients were randomly assigned to receive 200mg of Tyvyt and either 7.5mg/kg (low-dose group) or 15mg/kg (high-dose group) of Byvasda. In the dose-expansion phase, the safety and efficacy of each dose group will be evaluated.
A total of 50 patients were enrolled in the study, with 29 patients in the low-dose group and 21 patients in the high-dose group. The safety profile of the combination therapy was consistent with what was previously reported in the clinical studies of Tyvyt and Byvasda, with no new or unexpected safety signals observed. The most common treatment-related adverse events (TRAEs) wereHypertension(32%), proteinuria (26%), fever (26%). The incidence of adverse events with grade ≥3 was 28.6% in the high-dose group and 13.8% in the low-dose group.
The overall response rate (ORR) was 34% (17/50), with ORRs of 31% and 38% in the low-dose and high-dose groups, respectively. The disease control rate (DCR) was 78% (39/50). The median progression-free survival (PFS) was 10.5 months (95% CI: 8.4-12.7), and the median overall survival (OS) was 20.2 months (95% CI: 16.1-24.3).
FurtherBiomarkerThe analysis shows,Patients with high CD137 levels (≥31.8 pg/mL) had longer PFS (mPFS: 14.2 vs 4.1 months, p=0.001) and OS (mOS: NR [not reached] vs 15.6 months, p=0.023). Additionally,TumorAnalysis of the tumor immune microenvironment (TiME) showed that a high density of M1 macrophages (CD68+, CD163-) in the stroma was associated with higher efficacy (p=0.033), longer PFS (p=0.024), and OS (p=0.046).
Sintilimab in combination with bevacizumab for first-line treatment of advanced hepatocellular carcinoma was approved for marketing in China in June 2021 and successfully included in the national medical insurance. Chinese Academy of Medical SciencesTumorProfessor Zhou Aiping from the hospital stated: "This study not only demonstrated the safety and efficacy data of sintilimab combined with different doses of bevacizumab but also identified predictive markers for the efficacy of the combination therapy.Biomarker", laying the foundation for more personalized treatments." (Bioon.com)