Preliminary results of sintilimab plus different dose of IBI305 (anti-VEGF monoclonal antibody) in patients with advanced hepatocellular carcinoma: A phase Ib study.

Abstract

3079 Background: The study aimed to evaluate the safety and efficacy of sintilimab, a PD-1 blockade, plus IBI305, a biosimilar candidate of bevacizumab, in patients (pts) with advanced hepatocellular carcinoma (HCC). Methods: Adults with histocytologically confirmed advanced or metastatic HCC were enrolled in this two-part study. Part 1 was dose escalation trial, with initial dose of sintilimab 200 mg plus IBI305 7.5 mg/kg, q3w (low-dose group). If tolerable, IBI305 was escalated to 15 mg/kg (high-dose group). In part 2 for extension, at least 20 pts were enrolled to each tolerable dose group. Results: As data cutoff (Jan. 7, 2020), 50 pts were enrolled, 29 in low-dose group and 21 in high-dose group. 41 patients were systemic treatment naïve. The median treatment cycle was 4 (range: 1-19) in low-dose group and 11 (range: 1-16) in high-dose group. Most TRAEs were G1-2 with the most common being hypertension (28.0%) and pyrexia (26.0%). Totally, the grade 3 or more TRAEs were occurred in 6 (12.0%) pts, including hypertension occurred in 2 (4%) pts. The objective response rate (ORR) per RECIST v1.1 was 24.1% (95%CI: 10.3 - 43.5) in low-dose group, and 33.3% (95% CI:13.3 - 59.0) in high-dose group. As with the cutoff date, the median PFS has not been reached and the 6-month PFS rates were 60.5% (95%CI 36.1, 78.0) and 75.8% (95% CI: 47.3, 90.2), respectively. Conclusions: The combination of sintilimab and IBI305 showed promising efficacy and favourable safety profile in advanced HCC in both low-dose and high-dose groups. The preliminary result of this study warrant further exploration of dose selection for anti-VEGF/VEGFR agent when combined with PD-1/PD-L1 antibody. Clinical trial information: NCT04072679 . [Table: see text]

Clinical Activity and Safety of Penpulimab (Anti-PD-1) With Anlotinib as First-Line Therapy for Unresectable Hepatocellular Carcinoma: An Open-Label, Multicenter, Phase Ib/II Trial (AK105-203)

“…This study achieved a similar efficacy compared to that of IMbrave150. Moreover, the overall ORRs of other first-line combination therapies in trials that are still ongoing have ranged from 29 to 54.2%, and those studies have been based primarily on western HCC patients ( 15 – 17 , 19 , 20 , 26 ). In the current study, more than 60% of the patients were HBV-positive, yet achieved an ORR of 31%, similar to the results of previous studies.…”

“…Subgroup analysis of IMbrave150 highlighted the efficacy and safety of treatment with atezolizumab plus bevacizumab in the Chinese HCC population (19), and more trials of PD-1/L1 inhibitors combined with anti-angiogenic drugs for HCC in China are underway, but the sample size of which is small (20)(21)(22). Current research of first-line immunotherapy for HCC patients in China is relatively limited; there remains an urgent need for additional effective and safe treatments of HCC.…”

Downstaging and Resection of Initially Unresectable Hepatocellular Carcinoma with Tyrosine Kinase Inhibitor and Anti-PD-1 Antibody Combinations

“…The TKIs used in this study were lenvatinib (8 mg/day regardless of patient body weight) or apatinib [22] (250 mg/day). Anti-PD-1 antibodies were intravenously administered as follows: nivolumab 3 mg/kg, or camrelizumab [23] 200 mg, every 2 weeks or pembrolizumab 200 mg, or sintilimab [24] 200 mg, every 3 weeks.…”

Immune checkpoint inhibitor plus tyrosine kinase inhibitor for unresectable hepatocellular carcinoma in the real world

“…It has been available for patients with advanced cancer in China since 2019. Preliminary results of a phase Ib study showed treatment with sintilimab plus VEGF mAb IB305 resulted in an ORR of 33.3% and a 6-month PFS of 60.5% in patients with advanced HCC (16). A phase 3 ORIENT-32 study evaluating the efficacy and safety of sintilimab plus IB305 as a first-line treatment for advanced HCC is underway (NCT03794440).…”