A Phase 1a/1b Open-Label, Multicenter, Dose Escalation, and Dose Expansion Trial to Evaluate the Safety and Activity of TEV-56278, as a Monotherapy and in Combination With Pembrolizumab in Participants With Selected Locally Advanced or Metastatic Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 22
- 主要终点
- Duration of Response (DOR) in the expansion phase
研究概览
简要总结
The primary objectives of this trial are to:
- Characterize the safety and tolerability of TEV-56278
- Determine the Recommended Phase 2 Dose (RP2D)
- Evaluate antitumor activity of TEV-56278 (Part 2 only)
- Determine the safety and tolerability of TEV-56278 in combination with pembrolizumab
- Determine a RP2D of TEV-56278 in combination with pembrolizumab
The secondary objectives of this trial are to:
- Characterize the serum pharmacokinetics of TEV-56278
- Evaluate the antitumor activity of TEV-56278
- Determine the safety and tolerability of TEV-56278
- Evaluate other measures of antitumor activity of TEV-56278
- Evaluate anti-tumor activity
Participants will be treated up to 12 months with a follow-up period of up to 12 months after last infusion. The total duration of the trial will be up to 25 months for individual participants.
Participants who exhibit a favorable benefit risk profile at the end of the 12 month trial treatment period may be offered an opportunity for an extended treatment period in which they can be treated for a maximum of 12 additional months (up to 26 additional cycles of TEV-56278).
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
- •Have an established histological diagnosis of selected solid tumor and must have received and progressed on established standard therapies or have been intolerant to such therapy or have been considered by the Investigator as ineligible for approved standard therapy
- •Have a life expectancy≥12 weeks at the time of the screening
- •Women of childbearing potential must agree to use highly effective methods of contraception for the course of the trial through 120 days after the last dose of trial medication
- •Males who are sexually active with women of childbearing potential must agree to use condoms and refrain from donating sperm for the course of the trial through 120 days after the last dose of trial medication
- •NOTE- Additional criteria apply, please contact the investigator for more information
排除标准
- •Has a history of systemic treatment therapy for cancer (including chemotherapy, immunotherapy, radiotherapy, or other investigational drug) or surgery within 4 weeks prior to baseline
- •Is currently receiving or has received hematopoietic colony-stimulating growth factors within 2 weeks before screening or transfusion support 4 weeks prior to screening
- •Has a diagnosis of immunodeficiency
- •Has active known autoimmune disease.
- •Has a history of or known active brain metastases and/or carcinomatous meningitis and/or leptomeningeal metastasis
- •Has active or uncontrolled serious infections requiring systemic therapy within 14 days prior to baseline
- •Has a history of clinically significant cardiovascular or cerebrovascular disease in previous 6 months prior to screening
- •Has evidence of clinically significant interstitial lung disease or active, noninfectious pneumonitis
- •Has a seizure disorder requiring therapy (such as steroids or antiepileptics)
- •NOTE- Additional criteria apply, please contact the investigator for more information
结局指标
主要结局
Duration of Response (DOR) in the expansion phase
时间窗: Up to 24 months after the 1st dose in the expansion phase
Recommended Phase 2 dose in combination with Pembrolizumab
时间窗: Up to 24 months after 1st dose
Incidence of AEs with CTCAE Grade≥3 in the escalation phase
时间窗: Up to 15 months after 1st infusion in the escalation phase
CTCAE: Common Terminology Criteria for Adverse Events
Incidence of dose modifications due to AEs in the escalation phase
时间窗: Up to 12 months after 1st infusion in the escalation phase
Incidence of SAEs in the escalation phase
时间窗: Up to 15 months after 1st infusion in the escalation phase
Incidence of AEs meeting protocol-defined DLT criteria in the escalation phase
时间窗: Up to 28 days after 1st infusion in the escalation phase
DLT: dose-limiting toxicity
Incidence of AEs leading to discontinuation in the escalation phase
时间窗: Up to 12 months after 1st infusion in the escalation phase
Recommended Phase 2 dose as monotherapy
时间窗: Up to 24 months after 1st infusion
Objective Response Rate (ORR) based on RECIST criteria in the expansion phase
时间窗: Up to 24 months after the 1st dose in the expansion phase
RECIST: Response Evaluation Criteria in Solid Tumors.
Incidence of AEs with CTCAE Grade≥3 in the combination phase
时间窗: Up to 15 months after 1st infusion in the combination phase
Incidence of SAEs in the combination phase
时间窗: Up to 15 months after 1st infusion in the combination phase
Incidence of AEs meeting protocol-defined DLT criteria in the combination phase
时间窗: Up to 28 days after 1st infusion in the combination phase
Incidence of AEs leading to discontinuation in the combination phase
时间窗: Up to 12 months after 1st infusion in the combination phase
Incidence of dose modifications due to AEs in the combination phase
时间窗: Up to 12 months after 1st infusion in the combination phase
次要结局
- Cmax(Predose up to Day 8)
- Incidence of AEs with CTCAE Grade≥3 in the expansion phase(Up to 24 months after 1st infusion in the expansion phase)
- Incidence of AEs leading to discontinuation in the expansion phase(Up to 12 months after 1st infusion in the expansion phase)
- Disease Control Rate (DCR) according to RECIST (v1.1) criteria(Up to 24 months after 1st infusion)
- Time to Respond (TTR) according to RECIST (v1.1) criteria(Up to 24 months after 1st infusion)
- AUC0-last(Predose up to Day 8)
- tmax(Predose up to Day 8)
- Incidence of dose modifications due to AEs in the expansion phase(Up to 12 months after 1st infusion in the expansion phase)
- Objective Response Rate (ORR) based on RECIST criteria in the escalation phase(Up to 24 months after 1st infusion in the escalation phase)
- Incidence of SAEs in the expansion phase(Up to 15 months after 1st infusion in the expansion phase)
- Objective Response Rate (ORR) based on RECIST criteria in the combination phase(Up to 24 months after 1st infusion in the combination phase)