A Three Arm, Randomized, Double-Blind, Multicenter, Phase 3 Study of HLX10(Anti-PD-1 Antibody) in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04(Avastin Biosimilar) Compared With Carboplatin+Pemetrexed in 1L Stage IIIB/IIIC or IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 643
- 试验地点
- 1
- 主要终点
- Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
研究概览
简要总结
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically or cytologically confirmed, Stage IIIB/IIIC or IV non-squamous NSCLC
- •Participants with no EGFR, ALK and ROS1 mutation.
- •Participants with no prior treatment for Stage IIIB/IIIC or IV non-squamous NSCLC
- •Measurable disease as defined by RECIST v1.1
- •Eastern Cooperative Oncology Group performance status 0 or 1
- •Adequate hematologic and end organ function
排除标准
- •Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
- •Active central nervous system metastases
- •Prior treatment with cluster of differentiation immune checkpoint blockade therapies or Bevacizumab
- •Has received a surgical operation within 4 weeks from the initial drug administration
- •Active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.
- •Currently having or have had interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity
- •Any active infection requiring systemic anti-infective therapy within 14 days prior to study drug administration
- •Uncontrollable active infection(s)
- •History of immunodeficiency, including HIV antibody positive
- •active hepatitis B; or hepatitis C virus infections
- •Has bleeding tendency
- •History of severe cardiovascular diseases
- •Known gastrointestinal diseases as follows, Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or > moderate esophageal varices
- •Pregnant or breastfeeding female
研究组 & 干预措施
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: HLX10, an engineered anti-PD-1 antibody (Drug)
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: HLX04, a bevacizumab biosimilar (Drug)
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Carboplatin (Drug)
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Pemetrexed (Drug)
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: HLX10, an engineered anti-PD-1 antibody (Drug)
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: HLX04, a bevacizumab biosimilar (Drug)
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Carboplatin (Drug)
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Pemetrexed (Drug)
Part 2-Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: HLX10, an engineered anti-PD-1 antibody (Drug)
Part 2-Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Carboplatin (Drug)
Part 2-Arm B (HLX10+HLX04 placebo+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Pemetrexed (Drug)
Part 2-Arm C (HLX10 placebo+HLX04 placebo+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 placebo and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Carboplatin (Drug)
Part 2-Arm C (HLX10 placebo+HLX04 placebo+Carboplatin+Pemetrexed)
Participants will receive IV infusion of HLX10 placebo and HLX04 placebo on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
时间窗: Baseline until disease progression or death, whichever occurs first (up to approximately 24months)
Part 1 Safety and tolerability of study treatment
时间窗: baseline to 21 days
次要结局
- Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria)(Baseline up to approximately 36 months)
- Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration(Baseline up to approximately 36 months)
- Part 2-Overall survival (OS), as a major secondary endpoint(Baseline until death (up to approximately 36 months))
- Part 1 and 2-Microsatellite instability(MSI)(Baseline)
- Part 1 and 2-Incidence rates of AEs and SAEs(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(Baseline until disease progression or death, whichever occurs first (up to approximately 36months))
- Part 2-PFS2 (assessed by IRRC)(Baseline up to approximately 36months)
- Part 1-Overall survival (OS)(Baseline up to approximately 36months)
- Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria)(Baseline up to approximately 36 months)
- Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate(Baseline up to approximately 36 months)
- Part 1 and 2-Tumor mutation burden(TMB)(Baseline)
- Part 1 and 2-PD-L1 expression level(Baseline)