A Randomized, Double-blind, Multi-center, Phase III Clinical Study Assessing the Efficacy and Safety of Sintilimab ± IBI305 Combined With Pemetrexed and Cisplatin in Patients With EGFR-mutant Locally Advanced or Metastatic Non-squamous Non-small Cell Lung Cancer Who Have Failed Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI) Treatment (ORIENT-31)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 492
- 试验地点
- 1
- 主要终点
- PFS (Progression Free Survival)
研究概览
简要总结
The anti-tumor activity of anti-PD-1 therapy and VEGF inhibitor in TKI-resistant EGFR-mutated non-squamous NSCLC Chinese patients will be investigated in this clinical trial.
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
- •Signed written informed consent before any trial-related processes;
- •Age ≥ 18 years and <75 years male or females;
- •Has a histologically or cytologically confirmed stage IIIB/IIIC (American Joint Committee on Cancer [AJCC] 8th edition) NSCLC that is unresectable and not fit for radical concurrent chemoradiotherapy, or metastatic / recurrent non-squamous NSCLC;
- •Patients with EGFR mutation confirmed by tumor histology or cytology or hematology prior to EGFR-TKI treatment
- •EGFR-TKI resistance, confirmed by RECIST 1.1
- •The investigator confirms at least one measurable lesion according to RECIST 1.
- •A measurable lesion located in the field of previous radiation therapy or after local treatment may be selected as a target lesion if progression is confirmed; The Eastern Cancer Cooperative Group (ECOG) performance score of 0 or 1;
- •Exclusion criteria:
- •Squamous cell > 10%. If small cell types are present, the subject is not eligible for inclusion.;
- •Has previously received systemic anti-tumor treatment other than EGFR-TKI for or advanced non-squamous NSCLC (including cytotoxic chemotherapy for radiotherapy, do not include other systemic treatment for other cured tumors);
- •Has previously received the following therapies: anti-PD-1, anti-PD-L1 or anti-PD-L2 drugs or any other stimulatory or inhibitory agents of T cell receptors (eg CTLA-4, OX-40, CD137);
- •Has received EGFR-TKI treatment within 2 weeks;
- •Diagnosed of immunodeficiency or has received systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drugs.
- •History of pneumonitis requiring steroid therapy or the presence of interstitial lung disease within 1 year prior to the first dose of study drugs;
- •Symptomatic central nervous system metastases (CNS) metastasis and/or cancerous meningitis.
- •Hemoptysis within 3 months,
- •Full-dose oral or parenteral anticoagulant or thrombolytic agent for 10 consecutive days within 2 weeks. prophylactic use of anticoagulants is allowed;
排除标准
- 未提供
研究组 & 干预措施
Sintilimab +IBI305+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: IBI305 15mg/kg IV Q3W
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
干预措施: Sintilimab (Drug)
Sintilimab +IBI305+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: IBI305 15mg/kg IV Q3W
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
干预措施: IBI305 (Drug)
Sintilimab +IBI305+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: IBI305 15mg/kg IV Q3W
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
干预措施: Pemetrexed (Drug)
Sintilimab +IBI305+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: IBI305 15mg/kg IV Q3W
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
干预措施: Cisplatin (Drug)
Sintilimab +Placebo2+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Sintilimab (Drug)
Sintilimab +Placebo2+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Pemetrexed (Drug)
Sintilimab +Placebo2+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Cisplatin (Drug)
Sintilimab +Placebo2+Pemetrexed+Cisplatin
Drug: Sintilimab 200mg IV Q3W Other Name: IBI308
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Placebo2 (Drug)
Placebo1+Placebo2+Pemetrexed+Cisplatin
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo1 Placebo1 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Pemetrexed (Drug)
Placebo1+Placebo2+Pemetrexed+Cisplatin
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo1 Placebo1 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Cisplatin (Drug)
Placebo1+Placebo2+Pemetrexed+Cisplatin
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo1 Placebo1 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Placebo1 (Drug)
Placebo1+Placebo2+Pemetrexed+Cisplatin
Drug: Pemetrexed 500mg/m2 IV Q3W
Drug: Cisplatin 75mg/m2 IV Q3W
Drug: Placebo1 Placebo1 IV Q3W
Drug: Placebo2 Placebo2 IV Q3W
干预措施: Placebo2 (Drug)
结局指标
主要结局
PFS (Progression Free Survival)
时间窗: Time from randomization to first documented disease progression (radiographic) assessed by Independent Imaging Assessment Committee (IRRC) or death due to any cause. up to 24month
次要结局
- TTR（Time to objective response )(For subjects with CR or PR, defined as the time from randomization to the first documented CR or PR up to 24 month.)
- OS (Overall Survival)(Time from randomization to the death of the subject due to any cause assessed up to 36 months.)
- ORR (overall response rate)(The proportion of subjects who have a complete response (CR) or a partial response (PR) assessed up to 24 months.)
- PFS (Progression Free Survival)(Time from randomization to first documented disease progression (radiographic) assessed by investigator or death due to any cause up to 24 month.)
- DCR(Disease control rate )(The proportion of subjects in the analysis population who had a complete response (CR) or partial response (PR) or stable disease (SD) up to 24 month.)
- DOR(Duration of response)(For subjects with CR or PR, defined as the time from the first documented CR or PR to disease progression or death up to 24 month.)