Evaluation of Trabedersen (OT-101) With Pembrolizumab in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer and Positive PD-L1
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 45
- 试验地点
- 1
- 主要终点
- Phase I: Dose Finding
研究概览
简要总结
The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are:
- What medical problems to participants have when taking OT101 together with Pembrolizumab?
- What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy?
- Does the combination therapy delay progression or relapse of the participant's Non-Small Cell Lung Cancer?
Participants will:
- Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion.
- Receive intravenous Pembrolizumab once every 6 weeks.
详细描述
The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are:
- What medical problems to participants have when taking OT101 together with Pembrolizumab?
- What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy?
- Does the combination therapy delay progression or relapse of the participants Non-Small Cell Lung Cancer?
Participants will:
- Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion.
- Receive intravenous Pembrolizumab once every 6 weeks.
In Phase I, dose escalation/de-escalation of OT101/Trabedersen is performed using a BOIN design to determine dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D) when combined with Pembrolizumab.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 19 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 19 years
- •Histologically/cytologically proven diagnosis of non-small cell lung cancer (NSCLC) with a PD-L1 of at least 1%
- •Metastatic disease or disease not amenable for curative intent therapy
- •No prior treatment for metastatic NSCLC. Early-stage disease therapy acceptable if completed at least six months prior and did not include immunotherapy.
- •Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- •Measurable disease by RECIST criteria
- •Adequate organ and marrow function as defined below:
- •Absolute neutrophil count ≥1,500/mm3
- •Platelets ≥100,000/mm3
- •Hemoglobin >9.0 mg/dL
- •Creatinine clearance > 60 ml/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
- •Total serum bilirubin <1.5 X upper limit of normal (ULN) except if known to have Gilbert's syndrome, then excluded if total bilirubin >2.5 X ULN
- •Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN; if participant has liver metastases, ≤5x ULN
- •For females of childbearing potential, negative serum or urine pregnancy test ≤7 days of treatment, & agree to use effective contraceptive during treatment & 90 days after end of treatment
- •Male participants must agree to use effective contraception during the trial & for 90 days after end of treatment
- •Able to give informed consent
排除标准
- •Received any systemic treatments including investigational agents within the last 28 days
- •Known hypersensitivity to any of the excipients of OT101 or pembrolizumab
- •Received radiotherapy within 14 days of the study intervention. Palliative radiation is allowed during the study with a 1-week washout
- •Pregnant or breast-feeding women
- •History of autoimmune diseases that required systemic treatment in the past 2 years with agents such as, but not limited to, corticosteroids or immunosuppressive drugs. Thyroid replacement for hypothyroidism, insulin treatment for type I diabetes or corticosteroids adrenal/pituitary insufficiency are allowed.
- •Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the protocol activities
- •Known active second malignancy that needs treatment. Exceptions include basal cell or squamous cancers of the skin, bladder or cervical carcinoma in situ, prostate cancer on hormone therapy alone.
- •Immunodeficiency diagnosis or receiving chronic steroids that exceed a dose equivalent to prednisone 10 mg daily
- •Symptomatic brain metastases. Asymptomatic metastases or having received treatment for brain metastases and are off steroid therapy is acceptable.
- •Known psychiatric or substance use that would interfere with the study requirements
- •Inability to co-operate with the requirements of the protocol
研究组 & 干预措施
Arm I: Dose Finding
Participants receive either 140, 190, or 250 mg/m2 intravenous OT-101/Trabedersen for up to 12 weeks using a 4 days on 10 days off dosing schedule. The dose level is determined according to the Bayesian optimal interval (BOIN) design with cohort size 3.
Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
干预措施: Trabedersen (Drug)
Arm I: Dose Finding
Participants receive either 140, 190, or 250 mg/m2 intravenous OT-101/Trabedersen for up to 12 weeks using a 4 days on 10 days off dosing schedule. The dose level is determined according to the Bayesian optimal interval (BOIN) design with cohort size 3.
Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
干预措施: Pembrolizumab (Drug)
Arm II: Treatment
Participants receive the recommended phase II dose of intravenous OT-101/Trabedersen (140, 190, or 250 mg/m2) until progression using a 4 days on 10 days off dosing schedule.
Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
干预措施: Trabedersen (Drug)
Arm II: Treatment
Participants receive the recommended phase II dose of intravenous OT-101/Trabedersen (140, 190, or 250 mg/m2) until progression using a 4 days on 10 days off dosing schedule.
Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Phase I: Dose Finding
时间窗: 18 months
Dose Limiting toxicity (DLT) and Maximum Tolerated Dose (MTD)
Phase II: Progression-Free Survival (PFS)
时间窗: 36 months
Progression-Free Survival (PFS) defined as first therapy until the first documentation of clinical progression, relapse, or death due to any cause. Participants not experiencing an event of interest will be right-censored at last known disease status
次要结局
- Best Overall Response(36 months)
- Disease Control(36 months)
- Duration of Response(36 months)
- Drug Toxicity(18 months)
- Overall Survival (OS)(48 months)