A Multicenter, Multi-Part, Phase 1/2 Study of EIK1005 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors, Including Checkpoint Inhibitor Naïve Participants With Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors
概览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 160
- 试验地点
- 12
- 主要终点
- Dose-Limiting Toxicity (DLT) - Part 1
概览
简要总结
The goal of this clinical trial is to determine the most effective dose of EIK1005 that a person can take safely. Additionally, this study will test how well EIK1005 is tolerated alone and in combination with pembrolizumab in treating patients with advanced cancer.
详细描述
This Phase 1/2 study (EIK1005-002) will investigate the safety and tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary clinical activity of EIK1005 as a monotherapy and in combination with pembrolizumab in participants with advanced solid tumors, including participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) Tumors.
The study will be conducted in 2 parts: Part 1 and Part 2, with Part 1 being further divided into Part 1A and Part 1B as described below:
- Part 1A (monotherapy dose escalation): participants will receive EIK1005 only.
- Part 1B (combination dose escalation): participants will receive EIK1005 in combination with pembrolizumab.
- Part 2 (dose optimization): participants will be randomized 1:1 to monotherapy with EIK1005 at one of the two selected doses from Part 1A to identify the dose of EIK1005 in monotherapy for subsequent studies.
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
- •is ≥ 18 years of age at the time of signing the informed consent.
- •has a life expectancy of at least 3 months.
- •has histologically or cytologically documented advanced (unresectable and/or metastatic) solid tumor. Part 1A: recommend that participants have archival tissue not more than 3 years old. Part 1B and Part 2: participant has locally confirmed Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) tumor. Participant must have archival tumor tissue (not more than 3 years old) for retrospective confirmation of MSI-H or dMMR tumor by a central laboratory.
- •In Part 1A, has received and then progressed after or is intolerant to at least 1 standard treatment regimen in the advanced setting. The participant does not have alternative therapeutic options per PI's medical judgement. Preference should be given to: (1) participants with MSI-H or dMMR cancers that have progressed after checkpoint inhibitor (CPI) therapy and (2) participants with microsatellite stable cells (MSS) cancers that have progressed following at least one regimen of platinum, alkylating or topoisomerase containing chemotherapy.
- •has measurable disease at baseline according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) as determined by the PI.
- •has an Eastern Cooperative Oncology Group (ECOG) score of 0 to
- •has an adequate organ and marrow function.
排除标准
- •has not recovered (i.e., to Grade ≤ 1 or to baseline) from prior anti-cancer therapy-induced adverse events (AEs).
- •has received prior treatment with Werner (WRN) inhibitor.
- •has a history of relevant drug hypersensitivity, ascertained or presumptive allergy/hypersensitivity to the active drug substance and/or formulation ingredients, history of serious allergic reactions leading to hospitalization, or any other allergic reaction in general.
- •In Parts 1B and Part 2 Rescue: diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study intervention.
- •has known additional malignancy that is progressing or has required active treatment within the past 3 years.
- •has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable (ie, without evidence of progression) for at least 4 weeks as confirmed by repeat imaging performed during the study screening, are clinically stable and have not required steroid treatment for at least 14 days before the first dose of study treatment.
- •has mean resting QTcF \> 470 ms (men and women) obtained from triplicate electrocardiograms (ECGs).
- •has active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Participants may enroll with the following conditions: Type 1 diabetes, hypothyroidism requiring hormone replacement, or skin disorders (vitiligo, psoriasis, or alopecia not requiring systemic treatment).
- •has history of (non-infectious) pneumonitis/pneumonitis/interstitial lung disease that required steroids or current pneumonitis/interstitial lung disease.
- •has active tuberculosis.
研究组 & 干预措施
Part 1A (Dose escalation, Monotherapy)
EIK1005 will be given as monotherapy in participants without alternative treatment options.
干预措施: EIK1005 (Drug)
Part 1B (Dose escalation, Combination with pembrolizumab)
EIK1005 will be given in combination with pembrolizumab to participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) solid tumors.
干预措施: EIK1005 (Drug)
Part 2 (Dose optimization, Monotherapy)
Participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) advanced solid tumors will be randomized to receive EIK1005 monotherapy at one of the two identified doses selected from Part 1A.
干预措施: EIK1005 (Drug)
Part 1B (Dose escalation, Combination with pembrolizumab)
EIK1005 will be given in combination with pembrolizumab to participants with Microsatellite Instability High (MSI-H) or Mismatch Repair Deficient (dMMR) solid tumors.
干预措施: pembrolizumab (KEYTRUDA® ) (Drug)
结局指标
主要结局
Dose-Limiting Toxicity (DLT) - Part 1
时间窗: 21 Days
A DLT is a protocol-defined adverse event occurring during the DLT observation period.
Adverse Events (AEs) - Part 1 and Part 2
时间窗: From the time of first dose of study medication through 30 days following cessation of study treatment.
Number of participants reporting adverse events or serious adverse events.
次要结局
- Duration of Response (DOR) - Part 1 and Part 2(Through study completion, an average of 2 years.)
- Objective Response (OR) - Part 1 and Part 2(Through study completion, an average of 2 years.)
- Disease Control (DC) - Part 1 and Part 2(Through study completion, an average of 2 years.)
- Progression-free survival (PFS) - Part 2(Through study completion, an average of 2 years.)
- Pharmacokinetic (PK) parameters of EIK1005 - AUC0-24 (Part 1 and Part 2)(Up to 1 year)
- Pharmacokinetic (PK) parameters of EIK1005 - AUCtau,ss (Part 1 and Part 2)(Up to 1 year)
- Pharmacokinetic (PK) parameters of EIK1005 - Cmax (Part 1 and Part 2)(Up to 1 year)
- Pharmacokinetic (PK) parameters of EIK1005 - tmax (Part 1 and Part 2)(Up to 1 year)
- Pharmacokinetic (PK) parameters of EIK1005 - t½ (Half-life) (Part 1 and Part 2)(Up to 1 year)