A Phase I Study of Durvalumab (MEDI4736) Plus Tremelimumab in Combination With Platinum-based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer and Performance Status 2
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 1
- 试验地点
- 1
- 主要终点
- Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability)
研究概览
简要总结
This study is designed to evaluate the safety and tolerability of durvalumab and tremelimumab in combination with intravenous (IV) carboplatin plus (+) etoposide in new patients with extensive-stage small cell lung cancer (ES-SCLC).
详细描述
This Phase I, multicenter, study is designed to evaluate the safety and tolerability of durvalumab (anti-programmed death-ligand 1 [PD-L1] antibody) and tremelimumab (anti-cytotoxic T-lymphocyte-associated protein 4 [CTLA-4] antibody) in combination with intravenous (IV) carboplatin plus (+) etoposide in treatment naïve patients with extensive-stage small cell lung cancer (ES-SCLC) and performance status 2 (PS2). Eighteen patients with untreated ES-SCLC and PS2 will be enrolled. Cohort 1, which includes the first 6 subjects, will receive IV carboplatin and etoposide Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression. If 2 out of 6 patients have dose-limiting toxicities, then the study will be closed. Cohort 2, which will include 12 additional subjects, will receive chemotherapy Q 3 weeks x 4 cycles. Durvalumab 1500 mg IV + tremelimumab 75 mg IV Q 3 weeks will be given with chemotherapy during cycles 3 and 4, then durvalumab 1500 mg + tremelimumab 75 mg will be administered Q 3 weeks during cycles 5 and 6. This will be followed by durvalumab 1500 mg IV Q 4 weeks until disease progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
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
- •Age ≥ 18 years old at time of study entry (consent) and adult male or female (For Nebraska, ≥19 years old)
- •Histologically or cytologically confirmed ES-SCLC
- •Tumor biopsy or cytology should be obtained within 8 weeks of initiation of treatment.
- •Brain metastases; must be asymptomatic or treated and stable, off steroids for at least 1 month prior to study treatment.
- •Have not received any prior therapy for SCLC, except palliative radiation. If the patient received radiation, there must be measurable disease outside the radiation field.
- •Measurable disease or evaluable disease based on RECIST Version 1.
- •Eastern Cooperative Oncology Group ECOG = 2
- •Body weight > 30 kg
- •No active secondary malignancy. Patients with other prior malignancies will be included, provided they have been disease-free for at least five years.
- •Adequate hematologic and end organ function
- •Women of childbearing potential must have a pregnancy test (urine or serum) proven negative within 14 days prior to registration.
排除标准
- •Participation in another clinical study with an investigational product during the last 28 days.
- •Any previous chemotherapy and /or immunotherapy for SCLC
- •Current or prior use (≤ 14 days before first doses of study drugs) of immunosuppressive medication.
- •Any concurrent chemotherapy, IP, biologic, or hormonal therapy for cancer treatment.
- •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 IP
- •History of leptomeningeal carcinomatosis
- •Paraneoplastic syndrome (PNS) of autoimmune nature, requiring systemic steroids or clinical symptomatology suggesting worsening of PNS
- •Active infection including tuberculosis, HIV, hepatitis B and C.
- •Active or prior documented autoimmune or inflammatory disorders
- •Uncontrolled cardiovascular disease
- •History of active primary immunodeficiency
- •Pregnant or lactating women
- •Known allergies, hypersensitivity, or intolerance to any of the study medications, excipients, or similar compounds.
研究组 & 干预措施
Cohort 1
Durvalumab 1500 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab maintenance monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after Cycle 4.
干预措施: Durvalumab in combination with carboplatin and etoposide (Combination Product)
Cohort 2
Durvalumab 1500 mg plus tremelimumab 75 mg via IV infusion every 3 weeks, starting on Week 7, for up to a maximum of 2 doses/cycles followed by durvalumab monotherapy 1500 mg via IV infusion every 4 weeks, starting 4 weeks after the last infusion of the combination.
干预措施: Durvalumab + Tremelimumab in combination with carboplatin and etoposide (Combination Product)
结局指标
主要结局
Incidence of Treatment-related Adverse Events with a Severity of 3 or higher (Safety and tolerability)
时间窗: 3 months
Evaluate the safety and tolerability profile of durvalumab + tremelimumab in combination with carboplatin and etoposide in ES-SCLC and PS2. Adverse events with a severity grade of 3 or higher per CTCAE guidelines will be used to assess this outcome.
次要结局
未报告次要终点