A Phase IIIb, Single-arm, Multi-center, International Study of Durvalumab in Combination With Platinum and Etoposide for the First Line Treatment of Patients With Extensive-stage Small Cell Lung Cancer (LUMINANCE)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 152
- 试验地点
- 1
- 主要终点
- Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs)
研究概览
简要总结
Study to determine the safety and tolerability profile of durvalumab with platinum (cisplatin or carboplatin) plus etoposide (EP) as first-line treatment in participants with extensive-stage small-cell lung cancer.
详细描述
The study will be conducted in North America, Europe and Turkey.
In this single arm study participants will be treated with with durvalumab alone and concurrently with platinum-based chemotherapy and etoposide during the study period until radiological disease progression, unless there is clinical progression, unacceptable toxicity, withdrawal of consent, or another discontinuation criterion is met, as per investigator assessment.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically- or cytologically-documented ES-SCLC (stage IV [T any, N any, M1 a/b], or with T3-4 due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan (Brain metastases; must be asymptomatic or treated and stable off steroids and anticonvulsants for at least 1 month prior to study treatment)
- •Participants must be considered suitable to receive a platinum-based chemotherapy regimen as 1st line treatment for the ES-SCLC. Chemotherapy must contain either cisplatin or carboplatin in combination with etoposide
- •World Health Organization/ Eastern Cooperative Oncology Group performance status of 0 to 2 at enrollment Baseline computed tomography/ magnetic resonance imaging results of the brain, chest and abdomen (including liver and adrenal glands) within 28 days prior to the treatment initiation
- •No prior exposure to immune-mediated therapy including, but not limited to, other anti- CTLA-4, anti-Programmed cell death-1 (PD-1), anti- Programmed cell death ligand-1 (PD-L1), and anti-PD-L2 (anti-PD-L2) antibodies, excluding therapeutic anticancer vaccines
- •Adequate organ and marrow function
- •Body weight > 30 kg
- •Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal participants
排除标准
- •History of allogeneic organ transplantation
- •Active or prior documented autoimmune or inflammatory disorders, systemic lupus erythematosus, sarcoidosis syndrome, or wegener syndrome
- •Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the participant to give written informed consent
- •History of another primary malignancy except for:
- •Malignancy treated with curative intent and with no known active disease ≥ 5 years before the first dose of Investigational medicinal product (IMP) and of low potential risk for recurrence
- •Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
- •Adequately treated carcinoma in situ without evidence of disease
- •History of leptomeningeal carcinomatosis and active primary immunodeficiency
- •Active infection including tuberculosis, hepatitis B, hepatitis C, human immunodeficiency virus
- •Any unresolved toxicity Common Terminology Criteria for Adverse Events Grade ≥ 2 from previous anticancer therapy
- •Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients
- •Received prior systemic therapy for ES-SCLC
- •Medical contraindication to platinum (cisplatin or carboplatin)-etoposide-based chemotherapy
- •Any concurrent chemotherapy, IMP, biologic, or hormonal therapy for cancer treatment. Concurrent use of hormonal therapy for non-cancer-related conditions is acceptable
- •Planned consolidation chest radiation therapy. Radiation therapy outside of the chest for palliative care is allowed but must be completed before first dose of the study medication
- •Receipt of live attenuated vaccine within 30 days prior to the first dose of in IMP
- •Major surgical procedure within 28 days prior to the first dose of IMP
- •Participants who have received prior immunotherapy agents including anti-PD-1 or anti PD-L1
- •Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab
- •Participation in another clinical study with an investigational product administered in the last 4 weeks
- •Female participants who are pregnant or breastfeeding or male or female participants of reproductive potential who are not willing to employ effective birth control from screening to 90 days after the last dose of durvalumab and 180 days after the last dose of etoposide
研究组 & 干预措施
Durvalumab - (cisplatin or carboplatin) - Etoposide
Participants will receive durvalumab dose A administered via intravenous (IV) infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w). Thereafter, durvalumab monotherapy will be continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria are met.
干预措施: Durvalumab (Drug)
Durvalumab - (cisplatin or carboplatin) - Etoposide
Participants will receive durvalumab dose A administered via intravenous (IV) infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w). Thereafter, durvalumab monotherapy will be continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria are met.
干预措施: Cisplatin (Drug)
Durvalumab - (cisplatin or carboplatin) - Etoposide
Participants will receive durvalumab dose A administered via intravenous (IV) infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w). Thereafter, durvalumab monotherapy will be continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria are met.
干预措施: Carboplatin (Drug)
Durvalumab - (cisplatin or carboplatin) - Etoposide
Participants will receive durvalumab dose A administered via intravenous (IV) infusion concurrently with platinum-based chemotherapy and etoposide every 3 weeks (q3w). Thereafter, durvalumab monotherapy will be continued every 4 weeks post-chemotherapy unless specific treatment discontinuation criteria are met.
干预措施: Etoposide (Drug)
结局指标
主要结局
Number of Participants With Incidence of Grade 3 or Higher Adverse Events (AEs)
时间窗: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Incidence of Grade 3 or higher adverse events to evaluate safety and tolerability profile of durvalumab + Platinum (cisplatin or carboplatin) plus etoposide (EP) treatment was assessed.
Number of Participants With Incidence of Immune Mediated Adverse Events (imAEs)
时间窗: From first dose of study treatment until 90 days after treatment discontinuation, up to 2.5 years.
Immune mediated adverse events (imAEs) were assessed to evaluate safety and tolerability profile of durvalumab + EP treatment. An imAE is defined as an AESI that is associated with drug exposure and is consistent with an immune-mediated mechanism of action (MOA) and where there is no clear alternate etiology.
次要结局
- Overall Survival (OS)(From first dose of study treatment to death, up to 2.5 years.)
- Number of Participants With Adverse Events and Serious Adverse Events(From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.)
- Percentage of Participants Alive and Progression-free at 12 Months From First Date of Treatment (PFS12)(From first date of study treatment until 12 months.)
- Percentage of Participants Alive at 12 Months From First Date of Treatment (OS12)(From first dose of study treatment till 12 months.)
- Objective Response Rate (ORR)(From screening until disease progression or the last evaluable assessment in the absence of progression, up to 2.5 years.)
- Percentage of Participants Remaining in Response, 12 Months After First Documented Objective Response (DoR12)(From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.)
- Number of Participants With Adverse Events of Special Interests(From first dose of study treatment until 90 days after discontinuation, up to 2.5 years.)
- Progression-free Survival (PFS)(From first dose of study treatment until disease progression or death, up to 2.5 years.)
- Duration of Response (DoR)(From the date of first documented response until the first date of documented progression or death in the absence of disease progression, up to 2.5 years.)