A Randomized, Double-Blind, Placebo-Controlled, Multi-Regional Phase III Clinical Study of Toripalimab Alone or in Combination With Tifcemalimab (JS004/TAB004) as Consolidation Therapy in Patients With Limited-Stage Small Cell Lung Cancer Without Disease Progression Following Chemoradiotherapy
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 发起方
- 入组人数
- 756
- 试验地点
- 155
- 主要终点
- OS
研究概览
简要总结
The Study is a Phase 3, randomized, three-arm, double-blind, placebo-controlled, multi-regional clinical research study to evaluate the safety and efficacy use of toripalimab alone or in combination with tifcemalimab as consolidation therapy in patients with limited-stage small cell lung cancer without disease progression following chemoradiotherapy.
Tifcemalimab is a monoclonal antibody against B and T lymphocyte attenuator (BTLA). Toripalimab is a monoclonal antibody against programmed death protein-1 (PD-1). Neither drug is approved for treatment of This combination regimen is investigational in limited stage-small cell lung cancer in any country.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must meet all of the following inclusion criteria to be enrolled:
- •Male or female with age ≥ 18 years old at the time of informed consent.
- •Histologically or cytologically confirmed LS-SCLC using the Veteran's Administration Lung Study Arm (VALSG) staging criteria (Appendix 3). Patients with TNM Stage I or II disease per AJCC 8th edition must be medically inoperable (as determined by the Investigator) or the patient must refuse surgery.
- •Received CRT defined as: (1) 4 cycles of chemotherapy consisting of carboplatin or cisplatin and intravenously administered etoposide; (2) a total radiation dose of 60-66 Gy for the standard once daily (QD) radiotherapy regimen or 45 Gy for the hyperfractionated twice daily (BID) radiotherapy regimen; (3) Patients must begin investigational interventions within 42 days of the last dose of chemotherapy.
- •Patients must have achieved a complete response (CR), partial response (PR), or stable disease (SD) after receiving curative platinum-based CRT and must not have developed progressive disease (PD) prior to study entry.
- •Eastern Cooperative Oncology Group (ECOG) performance status (PS) score of 0-1 .
- •Adequate organ function
- •Female patients of childbearing potential and male patients whose partners are women of childbearing age.
- •Voluntarily agree to participate in the study, sign the informed consent form, and agree to comply with all study and follow-up procedures.
排除标准
- •Patients will be excluded from the study if they meet any of the following criteria.
- •Mixed SCLC and non-small cell lung cancer (NSCLC).
- •Received sequential chemoradiotherapy for LS-SCLC.
- •Failure to recover from toxicity of prior anticancer therapy to Common Terminology Criteria for Adverse Events (CTCAE) Grade ≤ 1 (except alopecia) or levels specified in the inclusion/exclusion criteria, whichever is more severe.
- •Patients with active autoimmune disease, history of autoimmune disease.
- •History of immunodeficiency, including HIV seropositivity, other acquired congenital immunodeficiency diseases, or a history of organ transplantation or allogeneic bone marrow transplantation.
- •History of confirmed or suspected interstitial lung disease or pneumonitis (except for Grade 1 radiation pneumonitis not treated with corticosteroids).
- •The presence of active hepatitis B (HBV DNA ≥ 500 IU/mL), hepatitis C (hepatitis C antibodies positive and HCV-RNA higher than the lower limit of detection of the analytical method).
- •Any other malignancy diagnosed prior to the first dose of investigational intervention, except those with a low risk for the development of metastases (5-year survival rate > 90%), such as adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix or breast, or adequately treated localized prostate cancer.
- •Women who are pregnant or breastfeeding.
研究组 & 干预措施
Experimental group A
Tifcemalimab (200 mg intravenous infusion [IV]) and toripalimab (240 mg IV)
干预措施: Tifcemalimab injection (Drug)
Experimental group A
Tifcemalimab (200 mg intravenous infusion [IV]) and toripalimab (240 mg IV)
干预措施: toripalimab injection (Drug)
Experimental group B
Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)
干预措施: toripalimab injection (Drug)
Placebo group C
Placebos for both tifcemalimab and toripalimab (IV)
干预措施: Placebo for toripalimab (Drug)
Experimental group B
Placebo for tifcemalimab (IV) and toripalimab (240 mg IV)
干预措施: Placebo for Tifcemalimab (Drug)
Placebo group C
Placebos for both tifcemalimab and toripalimab (IV)
干预措施: Placebo for Tifcemalimab (Drug)
结局指标
主要结局
OS
时间窗: up to 3years
To compare and evaluate the efficacy of toripalimab (Arm B) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by OS"
Overall survival (OS)
时间窗: up to 3years
To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after chemoradiotherapy (CRT) for patients with LS-SCLC as measured by OS
Progression-free survival (PFS)
时间窗: up to 2years
To compare and evaluate the efficacy of tifcemalimab and toripalimab (Arm A) versus placebo (Arm C) as consolidation therapy after CRT for patients with LS-SCLC as measured by Blinded Independent Review Committee (BIRC)-assessed PFS.
次要结局
- 2 year OS rate(up to 2 years)
- ORR(up to 2 years)
- DoR(up to 2 years)
- 1-year OS rate(up to 1year)
- objective response rate (ORR)(up to 2 years)
- 2-year OS rate(up to 2 years)
- disease control rate (DCR)(up to 2 years)
- 1 year OS rate(up to 1 years)
- duration of response (DoR)(up to 2years)
- PFS(up to 2 years)
- DCR(up to 2 years)
- safety(up to 2 years)
- PFS(up to 2years)
- Safety（adverse events and abnormal laboratory parameters）(up to 2 years)