104P - Safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment for metastatic colorectal cancer: A randomised, double-blind phase III study

Background

HLX04, a proposed bevacizumab biosimilar, was developed stepwise with proven analytical and clinical PK similarities. This confirmatory ph3 study (NCT03511963) aimed to compare the safety and efficacy of HLX04 versus reference bevacizumab in combination with XELOX or mFOLFOX6 as first-line treatment in pts with recurrent/metastatic colorectal cancer.

Methods

We conducted this double-blind, multicentre, parallel-controlled, ph3 study (HLX04-mCRC03) in pts (18≤age≤75 years) with histologically/cytologically confirmed unresectable recurrent/metastatic CRC. Eligible subjects were randomised 1:1 to receive either HLX04 or bevacizumab intravenously (7.5 mg/kg Q3W in combination with XELOX or 5 mg/kg Q2W in combination with mFOLFOX6). The primary endpoint was the progression free survival rate at week 36 (PFSR_36w) per RECIST v1.1. Secondary endpoints included ORR, 12-month OS rate and DoR. Primary and secondary endpoints were further stratified (by chemotherapy, KRAS/BARF mutation, etc.) for subgroup analyses.

Results

PFSR_36w was 46.4% (n=338) in HLX04 and 50.7% (n=337) in bevacizumab per FAS. The group difference was -4.2% (90% CI -10.6%, 2.1%), which fell entirely in the pre-defined equivalence margins (-11%, 15%). No statistically significant difference was observed in primary or secondary endpoints and their subgroup analyses. Similar safety results were demonstrated between the two treatment groups. The most common TEAEs (grade≥3) in both groups were decreased neutrophil count (20.6% vs 20.2%), decreased platelet count (10.3% vs 10.1%) and hypertension (7.4% vs 12.5%). The most common SAEs in both groups were intestinal obstruction (9.0% vs 9.6%) and decreased platelet count (11.2% vs 6.7%). The incidences of death during the treatment was 11 (3.2%) and 9 (2.7%), respectively. The immunogenicity profiles were similar between treatment groups.

Conclusions

HLX04 demonstrated equivalent efficacy and similar safety and immunogenicity profiles with reference bevacizumab as first-line treatment for mCRC, presenting as an alternative option for cancer pts as a biosimilar candidate.

Clinical trial identification

NCT03511963; April 30, 2018.

Editorial acknowledgement

Legal entity responsible for the study

Shanghai Henlius Biotech, Inc.

Funding

Shanghai Henlius Biotech, Inc.

Disclosure

L. Zhang, W. Li, K. Chai: Full/Part-time employment: Shanghai Henlius Biotech, Inc. W. Jiang, S. Liu: Shareholder/Stockholder/Stock options, Full/Part-time employment: Shanghai Henlius Biotech, Inc. All other authors have declared no conflicts of interest.