A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab (Anti-PD-1 Humanized Monoclonal Antibody Injection) and Chemotherapy in Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) Patients
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 132
- 试验地点
- 3
- 主要终点
- Dose-limiting toxicity (DLT) (Part 1)
研究概览
简要总结
A Phase II Study to Evaluate the Efficacy, Safety and Tolerability of HLX26 (Anti-LAG-3 Monoclonal Antibody Injection) Combined With Serplulimab (Anti-PD-1 Humanized Monoclonal Antibody Injection) and Chemotherapy in Previously Untreated Advanced Non-small Cell Lung Cancer (NSCLC) Patients
详细描述
This study is a phase II study to evaluate the efficacy, safety and tolerability of HLX26 in combination with Serplulimab and chemotherapy in the treatment of patients with Non-small cell lung cancer.
The trial was divided into period 1 (safety run-in phase) and period 2 (dose expansion phase).
The first phase is an open-label study, patients will receive varying doses (800 mg, 600 mg or lower) of HLX26 combined with a fixed dose (300 mg) of serplulimab and chemotherapy, administered by intravenous infusion every 3 weeks. Observation period of DLT lasts for 3 weeks after the first administration of HLX26. Safety review committee (SRC) will responsible for the safety of combination treatment. After confirmation of the safety, the efficacy of HLX26 combined with Serplulimab and chemotherapy will be evaluated in period 2.
The second phase (dose expansion phase) is a randomized, double-blind, placebo-controlled study to evaluate the safety and efficacy of 2 dose levels of HLX26 combined with fixed-dose (300 mg) of serplulimab and chemotherapy in patients with NSCLC. If the tolerability observation of the 600mg dose group is completed in the first phase, the SRC will review the safety data obtained from the study and decide whether to enter into the second phase; if 2 of the 6 subjects in the 600mg dose group in the first phase occur DLT event, we will continue to explore the safe dose of HLX26 and enroll another 3-6 subjects. Once the maximum tolerated dose (MTD) is found, two doses, MTD and MTD-1, will be selected to enter the dose expansion phase. (The SRC will review the safety and tolerability results obtained in the study to determine the MTD, and will select the dose of MTD-1 below the MTD and within the effective dose range). In the second stage, there are 3 groups and 40 people in each group. The interactive network/voice response system (IWRS) is used to randomly assign qualified subjects to the following three groups in a 1:1:1 allocation ratio:
> Group A: HLX26 MTD intravenous infusion + serplulimab 300 mg intravenous infusion, Q3W; chemotherapy
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
- Triple (Participant, Care Provider, Investigator)
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
- •Stage IV (AJCC 8th Edition) non-small cell lung cancer confirmed by histology or cytology.
- •No EGFR sensitive mutation or ALK, ROS1 rearrangement.
- •Have not received systemic treatment for stage IV disease. For patients who have received adjuvant or neoadjuvant treatment, if the adjuvant/neoadjuvant treatment has been completed for at least 6 months, they are allowed to be enrolled.
- •At least one measurable lesion evaluated by the investigator per RECIST v1.
- •Subjects must provide qualified tumor tissue samples for the detection of PD-L1 and LAG-3 expression level.
- •Have adequate organ function with expected survival period ≥ 12 weeks and ECOG score of 0 or
排除标准
- •Subjects with other histopathological types including small cell lung cancer, neuroendocrine cancer or sarcoma.
- •Have other malignant tumors within 3 years.
- •Pleural effusion, pericardial effusion or ascites that require clinical intervention.
- •Myocardial infarction and poorly controlled arrhythmia occurred within six months before the first administration of the study drug.
- •III - IV cardiac insufficiency per NYHA standard or left ventricular ejection fraction<50%.
- •Patients with active pulmonary tuberculosis.
- •Patients with previous or current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis, or severe pulmonary function impairment that may interfere with the detection and management of suspected drug-related pulmonary toxicity.
- •Patients who have known active autoimmune diseases or suspected auto-immue disease. Patients in stable condition and do not require systemic immunosuppressant therapy are allowed to be enrolled.
- •Require systemic treatment with corticosteroids (> 10 mg/day prednisone or equivalent) or other immunosuppressive agents within 14 days prior to the first dose of the study products or during the study.
- •Patients who have received any T-cell costimulatory agents or immune checkpoint blockade therapy, including but not limited to cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) inhibitors, PD-1 inhibitors, PD-L1 inhibitors.
- •Patients with a history of severe allergy to any monoclonal antibody products.
研究组 & 干预措施
HLX26 MTD + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: HLX26 (Drug)
HLX26 MTD + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Serplulimab (Drug)
HLX26 MTD + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Chemotherapy drug (Drug)
HLX26 MTD-1 + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD-1) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD-1) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: HLX26 (Drug)
HLX26 MTD-1 + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD-1) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD-1) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Serplulimab (Drug)
HLX26 MTD-1 + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, HLX26 (MTD-1) in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of HLX26 (MTD-1) in combination with Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Chemotherapy drug (Drug)
placebo + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, placebo in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Serplulimab (Drug)
placebo + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, placebo in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Chemotherapy drug (Drug)
placebo + serplulimab 300 mg + chemotherapy intravenous infusion Q3W
In this group, placebo in combination with HLX10 (300 mg) and chemotherapy will be intravenously administered every 3 weeks. About 40 subjects will be enrolled in this cohort. Patients will be treated with until disease progression, death, receiving new antitumor treatment, intolerable toxicity or withdrawal of informed consent (whichever occurs first). The efficacy of Serplulimab and chemotherapy will be evaluated in this group.
干预措施: Placebo (Drug)
结局指标
主要结局
Dose-limiting toxicity (DLT) (Part 1)
时间窗: from day1 to day 21
The DLT of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients
Objective Response Rate (ORR) per RECIST 1.1 as Assessed by IRRC ( Part 2)
时间窗: approximately up to 12 months
The ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by IRRC.
Maximum Tolerated Dose (MTD) (Part 1)
时间窗: from day1 to day 21
The MTD of HLX26 in combination with Serplulimab and Chemotherapy within 3 weeks after the first administration in previously untreated NSCLC patients
次要结局
- Disease Control Rate (DCR) per RECIST 1.1 as Assessed by IRRC and Investigator(approximately up to 12 months)
- Adverse events(approximately up to 12 months)
- Immunogenicity of HLX26(approximately up to 12 months)
- Duration of Response (DOR) per RECIST 1.1 assessed by IRRC and Investigator(approximately up to 12 months)
- Objective Response Rate (ORR) per RECIST 1.1 assessed by Investigator(approximately up to 12 months)
- Overall Survival (OS)(approximately up to 36 months)
- Progression Free Survival (PFS) per RECIST 1.1 assessed by IRRC and Investigator(approximately up to 12 months)
- Serum concentration of HLX26 and Serplulimab(approximately up to 12 months)