This study involves a two-part design. Part 1 is designed to evaluate the safety and tolerability of the 4 drug (HLX10+HLX04+carboplatin+pemetrexed). Part 2 is a randomized, open-label study, which will evaluate the safety and efficacy of HLX10 in combination with carboplatin+pemetrexed with or without HLX04(biosimilar of avastin) compared with treatment with carboplatin+pemetrexed in 1st line Stage IIIB/IIIC or IV non-squamous NSCLC. Participants will be randomized in a 1:1:1 ratio to Arm A (HLX10+HLX04+Carboplatin+Pemetrexed), Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed), or Arm C (HLX10 placebo + HLX04 placebo+Carboplatin+Pemetrexed).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
643
HLX10 will be administered as IV infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until loss of clinical benefit or up to 2 year.
HLX04 will be administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
Carboplatin will be administered at area under the concentration-time curve (AUC) 5 on Day 1 of each 21-day cycle for 4 cycles, or until loss of clinical benefit whichever occurs first.
Pemetrexed will be administered as IV infusion at a dose of 500 milligrams per square meter (mg/m2) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
Cancer Hospital Chinese Academy of Medical Sciences (CAMS)
Beijing, Beijing Municipality, China
Part 1 Safety and tolerability of study treatment
Time frame: baseline to 21 days
Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 24months)
Part 2-Overall survival (OS), as a major secondary endpoint
Time frame: Baseline until death (up to approximately 36 months)
Part 1 and 2-Incidence rates of AEs and SAEs
Time frame: Baseline up to approximately 36months
Part 1-Overall survival (OS)
Time frame: Baseline up to approximately 36months
Part 1 and Part 2-PFS (assessed by the investigator according to RECIST v1.1) in Part 1 and 2; PFS (assessed by IRRC according to RECIST v1.1) in Part 1
Time frame: Baseline until disease progression or death, whichever occurs first (up to approximately 36months)
Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria)
Time frame: Baseline up to approximately 36 months
Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria)
Time frame: Baseline up to approximately 36 months
Part 2-PFS2 (assessed by IRRC)
Time frame: Baseline up to approximately 36months
Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration
Time frame: Baseline up to approximately 36 months
Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate
Time frame: Baseline up to approximately 36 months
Part 1 and 2-PD-L1 expression level
Time frame: Baseline
Part 1 and 2-Microsatellite instability(MSI)
Time frame: Baseline
Part 1 and 2-Tumor mutation burden(TMB)
Time frame: Baseline
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