A Phase 1A/B Study to Evaluate the Safety and Tolerability of ETC-1922159 as a Single Agent and in Combination With Pembrolizumab in Advanced Solid Tumours
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 89
- 试验地点
- 11
- 主要终点
- Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Expansion)
研究概览
简要总结
This is a Phase 1A/B study consisting of four parts.
- Part A (completed) is a non-randomised, open-label, sequential evaluation of the safety, pharmacokinetics (PK), maximum tolerated dose (MTD), and recommended dose (RD) of ETC-1922159 in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available. Dose escalation, with the goal of identifying the MTD and RD, is guided by an ordinal continual reassessment method (oCRM) model with a cohort size of one patient.
- Part A extension (completed) is a non-randomised, non-comparative, open-label evaluation of the safety and tolerability of ETC-1922159 together with the bone protective treatment (denosumab) in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
- Part B dose escalation (completed) is a non-randomised, open-label, sequential evaluation of the MTD, RD, safety, PK, and PD (pharmacodynamics) of ETC 1922159 in combination with pembrolizumab in patients with advanced or metastatic, or unresectable solid malignancies, for whom no approved treatment option or standard of care is available.
- Part B dose expansion will be a non-randomised, non-comparative, open-label study evaluation of the safety and tolerability of ETC-1922159 as a single agent until disease progression and then in combination with pembrolizumab at the RD identified in the Part B dose escalation segment, in patients with advanced or metastatic, or unresectable solid malignancies that are refractory, intolerant or not suitable for available treatment according to the treating physician.
It is anticipated that the study will take approximately 78 months to complete (36 months for Part A and Part A Extension, approximately 6 months for Part B dose escalation and approximately 36 months for Part B dose expansion).
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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Dose Escalation
ETC-1922159 + pembrolizumab
干预措施: Pembrolizumab (Drug)
Dose Escalation
ETC-1922159 + pembrolizumab
干预措施: ETC-1922159 (Drug)
Dose Expansion
ETC-1922159 as single agent until disease progression, then in combination with pembrolizumab at the recommended dose (RD) identified in the dose escalation segment
干预措施: ETC-1922159 (Drug)
Dose Expansion
ETC-1922159 as single agent until disease progression, then in combination with pembrolizumab at the recommended dose (RD) identified in the dose escalation segment
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Maximum Tolerated Dose (MTD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation)
时间窗: For 2 cycles (42 days)
Recommended Dose (RD) of ETC-1922159 when administered with pembrolizumab (Part B Dose Escalation)
时间窗: For 2 cycles (42 days)
Change in Eastern Cooperative Oncology Group performance status (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Number of participants with abnormal clinical laboratory test results (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Number of participants with adverse events (AEs) (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Number of participants with abnormal vital sign measurements (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
Tolerability measured by monitoring of fatigue and gastrointestinal-related side effects and when applicable, immune-related side effects in patients (Part B Dose Expansion)
时间窗: From date of enrolment until end of treatment
次要结局
- Number of participants with abnormal 12-lead electrocardiogram (ECG) readings (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Number of participants with adverse bone density imaging assessments via DEXA scan (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Number of participants with abnormal vital sign measurements (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Number of participants with adverse events (AEs) (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Change in Eastern Cooperative Oncology Group performance status (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Tolerability measured by monitoring of fatigue and gastrointestinal-related side effects and when applicable, immune-related side effects in patients (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Clinical activity measured by RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 and iRECIST (Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics) (Part B Dose Expansion)(From date of enrolment until end of treatment)
- Retrospective evaluation of plasma/serum concentration of bone protective agents, if administered (Part B)(Before and after the first administration only)
- Number of participants with abnormal clinical laboratory test results (Part B Dose Escalation)(From date of enrolment until end of treatment)
- Clinical activity measured by RECIST (Response Evaluation Criteria in Solid Tumours) version 1.1 and iRECIST (Response Evaluation Criteria in Solid Tumours modified for immune-based therapeutics) (Part B Dose Escalation)(From date of enrolment until end of treatment)
- ETC-1922159 Maximum plasma concentration (Cmax) (Part B)(From date of enrolment until end of treatment)
- ETC-1922159 Area under the curve (AUC) (Part B)(From date of enrolment until end of treatment)
- Retrospective evaluation of plasma/serum concentration of pembrolizumab (Part B)(From date of enrolment to Cycle 2 for Dose Escalation and Cycle 1 of combination therapy for Dose Expansion)