A Randomized, Double-blind, Multi-center, Phase III Study of AK112 Combined With Pemetrexed and Carboplatin Versus Placebo Combined With Pemetrexed and Carboplatin in Patients With Locally Advanced or Metastatic EGFR-mutant Non-squamous NSCLC Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors (EGFR-TKIs)
概览
- 阶段
- 3 期
- 干预措施
- Ivonescimab (SMT112 or AK112) Injection
- 疾病 / 适应症
- Non-Squamous Non-small Cell Lung Cancer
- 发起方
- Akeso
- 入组人数
- 322
- 试验地点
- 1
- 主要终点
- Progression-free survival (PFS)
- 状态
- 进行中（未招募）
- 最后更新
- 上个月
概览
简要总结
A Randomized, Double-blind, Multi-center, Phase III Clinical Study of AK112 or Placebo Combined With Pemetrexed and Carboplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed to Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment
详细描述
The trial will be performed as a randomized, Double-Blind, Multicenter trial to compare AK112 Plus Pemetrexed and Carboplatin to Placebo Plus Pemetrexed and Carboplatin in Patients with Locally Advanced or Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC) Harboring. Approximately 320 subjects will be randomized to the two treatment at the ratio of 1:1. Each enrolled subject will receive an intravenous infusion of the AK112/Placebo Plus Pemetrexed and Carboplatin （Q3W,up to 4 cycles）in treatment periods per the randomization schedule. Afterward, AK112/ Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
研究者
入排标准
入选标准
- •Ability to understand and voluntarily sign a written informed consent form (ICF), which must be signed before the specified study procedures required for the study are performed.
- •Males or females aged ≥ 18 to ≤ 75 years at the time of signing informed consent.
- •Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) 0 or
- •Life expectancy ≥3 months；
- •Locally advanced (stage IIIB/IIIC) or metastatic (stage IV) non-squamous NSCLC confirmed by histology or cytology, inoperable and unable to receive radiotherapy and chemotherapy;
- •The tumor histology, cytology or hematology confirmed the presence of EGFR activating mutations before enrollment
- •Have previously received EGFR-TKI treatment and the treatment has failed
- •Subjects have at least one measurable non-brain tumor lesion per RECIST v1.1
- •Major organ function prior to treatment meets the following criteria
- •Patients of childbearing potential must agree to use effective contraceptive measures
排除标准
- •Histological or cytological pathology confirmed the presence of small cell carcinoma components, or the main component is squamous cell carcinoma
- •There are reports confirming the existence of other driver gene mutations with known drug treatments
- •Subjects who received any prior treatments targeting the mechanism of tumor immunity
- •The subject has received systemic anti-tumor therapy other than EGFR-TKI
- •Currently enrolled in any other clinical study
- •Received EGFR-TKI treatment, palliative local treatment, non-specific immunomodulatory treatment within 2 weeks prior to the first dose; and Chinese herbal medicine or traditional Chinese medicinal products with anti-tumor indications within 1 weeks prior to the first dose.
- •Tumor surrounds important blood vessels or has obvious necrosis, cavitation, or invades surrounding important organs and blood vessels.
- •Symptomatic central nervous system metastases
- •Active malignancies within the past 3 years, with the exception of tumors in this study and cured local tumors
- •Active autoimmune disease requiring systemic treatment within 2 years prior to the start of study treatment
研究组 & 干预措施
Ivonescimab (SMT112 or AK112) in combination with Pemetrexed and Carboplatin
Subjects will receive Ivonescimab (SMT112 or AK112) Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles. Afterward, AK112 Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
干预措施: Ivonescimab (SMT112 or AK112) Injection
Placebo in combination with Pemetrexed and Carboplatin
Subjects will receive Placebo Plus Pemetrexed and Carboplatin via intravenous infusion (IV) Q3W, up to 4 cycles in treatment periods per the randomization schedule. Afterward, Placebo Plus Pemetrexed will be used for maintenance treatment (administered on Day 1 of each cycle, Q3W) up to 2 years.
干预措施: Placebo Injection
结局指标
主要结局
Progression-free survival (PFS)
时间窗: Up to 2 years
Progression-free survival (PFS) assessed by IRC per RECIST v1.1 in the ITT population.
次要结局
- DoR(Up to 2 years)
- OS(Up to 2 years)
- ORR(Up to 2 years)
- TTR(Up to 2 years)
- AE(From the subject signs the ICF to 30 days (AE) and 90 days (SAE) after the last dose of study treatment or initiation of other anti-tumor therapy, whichever occurs first,up to 2 years)
- Observed concentrations of AK112(through study completion, an average of 2 year)
- Number of subjects who develop detectable anti-drug antibodies (ADAs)(From first dose of AK112 through 90 days after last dose of AK112,up to 2 years)
- DCR(Up to 2 years)
- PFS(Up to 2 years)