A Phase I, Open-label, Multiple-ascending Dose Trial to Investigate the Safety, Tolerability, Pharmacokinetics, Biological and Clinical Activity of MSB0011359C (M7824) in Subjects With Metastatic or Locally Advanced Solid Tumors With Expansion to Selected Indications in Asia
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 114
- 试验地点
- 18
- 主要终点
- Number of Participants With Dose Limiting Toxicity (DLT)
研究概览
简要总结
The main purpose of this study was to assess the safety and tolerability of MSB0011359C. Study consists of dose-escalation part and an expansion part in participants with metastatic or locally advanced solid tumors, for which no standard effective therapy exists or a standard therapy had failed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Able and willing to give written informed consent and had signed the appropriate written informed consent form (ICF), prior to performance of any trial activities
- •Eligible male and female participants aged greater than or equal to (>=)20 years
- •Histologically or cytologically proven metastatic or locally advanced solid tumors, for which no effective standard therapy exists or standard therapy had failed
- •Eastern Cooperative Oncology Group performance status (ECOG) performance status of 0 to 1 at trial entry
- •Life expectancy >=12 weeks as judged by the Investigator.
- •Adequate hematological function defined by white blood cell (WBC) count >=3*10^9/Liter with absolute neutrophil count (ANC) >=1.5*10^9/Liter, lymphocyte count >=0.5* 10^9/Liter, platelet count >=75*10^9/Liter, and Hemoglobin (Hgb) >= 9 grams per deciliter (g/dL) (in absence of blood transfusion)
- •Adequate hepatic function defined by a total bilirubin level <=1.5 × Upper limit of normal (ULN), an AST level <= 2.5 × ULN, and an ALT level <= 2.5 × ULN
- •Adequate renal function defined by an estimated creatinine clearance >50 milliliter per minute (mL/min) according to the Cockcroft-Gault formula or by measure of creatinine clearance from 24 hour urine collection
- •Other protocol-defined exclusion criteria could apply.
排除标准
- •Concurrent treatment with non-permitted drugs and other interventions
- •Anticancer treatment within 28 days before the start of trial treatment, for example cyto reductive therapy, radiotherapy (with the exception of palliative bone directed radiotherapy), immune therapy, or cytokine therapy
- •Major surgery within 28 days before the start of trial treatment (excluding prior diagnostic biopsy)
- •Systemic therapy with immunosuppressive agents within 7 days before the start of trial treatment; or use of any investigational drug within 28 days before the start of trial treatment
- •Previous malignant disease other than the target malignancy to be investigated in this trial with the exception of cervical carcinoma in situ and superficial or non invasive bladder cancer (treated with curative intent) within the last 5 years or basal cell or squamous cell carcinoma in situ within the last 3 years
- •Rapidly progressive disease which, in the opinion of the Investigator, may predispose to inability to tolerate treatment or trial procedures
- •Active or history of central nervous system metastases, except as in the melanoma-specific Central nervous system (CNS) criteria listed above
- •Receipt of any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immunosuppression (eg, corneal transplant, hair transplant)
研究组 & 干预措施
MSB0011359C (M7824)
干预措施: MSB0011359C (Drug)
结局指标
主要结局
Number of Participants With Dose Limiting Toxicity (DLT)
时间窗: Baseline up to Week 3
A DLT was defined as any grade greater than or equal to (\>=) 3 adverse event suspected to be related to investigational medicinal product (IMP) by the Investigator and / or Sponsor occurring in the DLT evaluation period confirmed by the Safety Monitoring Committee (SMC) to be relevant for the IMP treatment.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) According to National Cancer Institute-Common Terminology Criteria for Adverse Event (NCI-CTCAE) Version 4.03
时间窗: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs.
Number of Participants With Treatment-Related Adverse Events (TRAEs) According to NCI-CTCAE Version 4.03
时间窗: First study drug administration up to 30 days after the last drug administration assessed up to approximately 5 years
An adverse event (AE) was any untoward medical occurrence in a clinical investigation participant administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. Serious AE: an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE: AE with onset after start of treatment or with onset date before the treatment start date but worsening after the treatment start date. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs: reasonably related to the study intervention. Number of participants with TEAEs and treatment related TEAEs were reported.
次要结局
- Dose-Escalation Phase: Maximum Serum Concentration (Cmax) of M7824(Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43)
- Dose-Escalation Phase: Terminal Half Life (t1/2) of M7824(Pre-dose, 0, 4 hour post dose on Day 1, 2,8,15,29,43)
- Dose-Escalation Phase: Area Under the Serum Concentration Time Curve From Zero to Last Sampling Time (AUC0-t) of M7824(Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43)
- Dose-Escalation Phase: Area Under The Concentration Time Curve From Time Zero to Infinity (AUC0-inf) of M7824(Pre-dose, 0, 4 hour post dose on Day 1, 2, 8, 15, 29, 43)
- Dose-Escalation Phase: Number of Participants With Positive Serum Titers of Anti-Drug Antibodies of M7824(Predose, Day 15, 43, 85 and every 6-weekly until progression or end of the treatment whichever occur first, assessed up to 3 years)
- Dose-Escalation Part: Number of Participants With Best Overall Response (BOR) As Assessed By Investigator(Date of randomization up to 2 years)
- Expansion Part: Best Overall Response (BOR) As Assessed By Investigator(Date of randomization up to 2 years)
- Expansion Part: BOR According to RECIST 1.1 As Adjudicated By The Independent Review Committee (IRC)(Up to 2 years)
- Expansion Part: Duration of Response (DOR)(Up to 2 years)
- Expansion Part: Disease Control Rate(Up to 2 years)
- Expansion Part: Progression Free Survival (PFS) Time(Date of randomization until death or progressive disease assessed up to 2 years)
- Expansion Part: Overall Survival (OS) Time(Date of randomization until death assessed up to 2 years)