A Ph1 Open-Label Multicentre Study to Assess Safety, Tolerability, PK and Anti-tumor Activity of Tremelimumab /Tremelimumab With MEDI4736 in Japanese With Advanced Solid Malignancies or Tremelimumab in Japanese With Malignant Mesothelioma
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- AstraZeneca
- 入组人数
- 65
- 试验地点
- 1
- 主要终点
- Adverse event
研究概览
简要总结
A Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, PK and Preliminary Anti-tumor Activity when given as a monotherapy of Tremelimumab or Tremelimumab in combination with MEDI4736 in Japanese Patients with Advanced Solid Malignancies, and when given as a monotherapy of tremelimumab in Second- or Third-line Treatment of Japanese Subjects with Unresectable Pleural or Peritoneal Malignant Mesothelioma
详细描述
Primary objectives Part A: To investigate the safety and tolerability of tremelimumab when given to Japanese patients with advanced solid malignancies and define the dose(s) for further clinical evaluation.
Part B: To investigate the safety and tolerability of tremelimumab in combination with MEDI4736 when given to Japanese patients with advanced solid malignancies and to define the dose(s) for further clinical evaluation.
Part C: To investigate the safety and tolerability of tremelimumab when given to Japanese patients with unresectable pleural or peritoneal malignant mesothelioma.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 130 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Japanese aged at least 20 years old at a time of enrollment.
- •Histological or cytological confirmation of a solid malignant tumor excluding lymphoma that is refractory to standard therapies or for which no standard therapies exist.
- •ECOG Performance Status 0-1 with no deterioration over the previous 2 weeks and minimum life expectancy of 12 weeks at a time of randomization.
- •At least one lesion (measurable and/or non-measurable) that can be accurately assessed at baseline by CT, MRI or plain X-ray and is suitable for repeated assessment.
- •Adequate bone marrow, hepatic, and renal function
- •Willingness to provide consent for archival biopsy samples if available.
排除标准
- •Received any prior treatment with monoclonal antibody against Programmed death 1 (PD1), Programmed death ligand 1 (PD-L1) and CTLA-4 (eg, ipilimumab)
- •The last dose of prior chemotherapy or radiation therapy was received less than 2 weeks prior to randomization 3 Currently receiving systemic corticosteroids or other immunosuppressive medications or has a medical condition that requires the chronic use of corticosteroids.
- •Receipt of live attenuated vaccination within 30 days of starting tremelimumab treatment
- •Active, untreated central nervous system (CNS) metastasis (subjects with brain metastases who are identified at screening
- •History of other malignancy unless the subject has been disease-free for at least 3 years.
- •Any unresolved chronic toxicity CTCAE grade ≥2 from previous anticancer therapy at the time of randomization,
- •Major surgical procedure within 30 days of starting
- •Inclusion Criteria:
- •Japanese aged 20 and over at the time of consent
- •Histologically and/or cytologically confirmed pleural or peritoneal malignant mesothelioma
- •Disease not amenable to curative surgery
- •ECOG Performance status 0-1
- •Progressed after previous receipt of 1-2 prior systemic treatments for advanced disease that included a first-line pemetrexed (or anti-folate)-based regimen in combination with platinum agent.
- •Measurable disease, defined as at least 1 lesion (measurable) that can be accurately assessed at baseline by computed tomography CT or MRI and is suitable for repeated assessment.
- •Adequate bone marrow, hepatic, and renal function Exclusion Criteria:
- •Subjects who failed more than 2 prior systemic treatment regimens for advanced malignant mesothelioma
- •Received any prior mAb against CTLA-4, PD1 or PD-L1
- •History of chronic inflammatory or autoimmune disease.
- •Symptomatic, untreated CNS metastasis.
- •Any serious uncontrolled medical disorder or active infection that would impair the subject's ability to receive investigational product.
- •History of other malignancy.
- •History of diverticulitis, inflammatory bowel disease, sarcoidosis syndrome
- •Currently receiving systemic corticosteroids or other immunosuppressive medications.
- •Vaccinated with live attenuated vaccines within 30 days prior to starting tremelimumab treatment
- •Not recovered from all toxicities associated with prior cancer treatment to acceptable baseline status, or a NCI CTCAE ver.3.0 Grade of 0 or 1
研究组 & 干预措施
Part A
Dose escalation of tremelimumab mono therapy for advanced solid malignancies
干预措施: Tremelimumab (Drug)
Part B
Combination therapy of tremelimumab and MEDI4736 for advanced solid malignancies
干预措施: Tremelimumab (Drug)
Part B
Combination therapy of tremelimumab and MEDI4736 for advanced solid malignancies
干预措施: MEDI4736 (Drug)
Part C
Fixed dose of tremelimumab for malignant mesothelioma
干预措施: Tremelimumab (Drug)
结局指标
主要结局
Adverse event
时间窗: From time of informed consent to 90 days after the last dose
To investigate the safety and tolerability of tremelimumab and/ or MEDI4736 when given to Japanese patients
次要结局
未报告次要终点