Dose Escalation and Expansion Clinical Study to Evaluate the Safety and Efficacy of ELU001 in Subjects Who Have Advanced, Recurrent or Refractory FRα Overexpressing Tumors
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 79
- 试验地点
- 18
- 主要终点
- Part 1 Dose Escalation: The Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors.
研究概览
简要总结
This study, ELU- FRα-1, was focused on adult subjects who have advanced, recurrent or refractory folate receptor alpha (FRα) overexpressing tumors considered to be topoisomerase 1 inhibitor-sensitive based on scientific literature, and, in the opinion of the Investigator, have no other meaningful life-prolonging therapy options available.
详细描述
The study had two parts: Part 1 Dose Escalation Safety Study to identify the maximum tolerated dose (MTD) and/or the recommended phase 2 dose (RP2D), and Part 2 Tumor Group Expansion Cohort(s) where specific cancer types will be evaluated for efficacy and safety at the RP2D.
Part 1, subjects with cancer types with a high likelihood of having FRα overexpressing tumors based on historical data, specifically, ovarian, endometrial, colorectal, gastric, gastroesophageal junction, triple negative breast, or non-small cell lung cancers, or cholangiocarcinoma, will be enrolled in a basket clinical study. Retrospective analysis of folate receptor alpha (FRα) expression status will be determined. Part 1 is currently closed for further recruitment.
Part 2 Stage 1 of a Simon's Two-Stage design, tumor group expansion cohorts, each consisting of subjects with cancer types studied as part of the basket in Part 1. Part 2 is closed for recruitment.
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
盲法说明
Open Label
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
- •Patients must meet the following criteria to enroll in this study:
- •Part 1 Documented diagnosis of ovarian cancer, endometrial cancer, colorectal cancer, gastric cancer, gastroesophageal junction cancer, triple negative breast cancer, non-small cell lung cancer, or cholangiocarcinoma
- •Part 2 Ovarian Cancer or Endometrial Cancer
- •No other meaningful life-prolonging therapy option available
- •Must provide archival tumor tissue or a newly obtained tumor biopsy specimen prior to the first dose of ELU001 for folate receptor alpha (FRα) expression analysis. Previous FRα expression test results may be used in certain circumstances
- •Adequate organ function
- •Measurable disease, or in the absence of measurable disease, non-measurable disease as per Response evaluation criteria in solid tumors (RECIST) v1.1
- •Part 1: Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2; Part 2: ECOG performance status of 0 or
- •Recovered from previous surgeries
- •Agree to highly effective contraception, not to get pregnant, or for men, not father a child during study participation
排除标准
- •Patients who meet any of the following are not eligible to enroll in this study:
- •Clinically significant eye disorders
- •Taken any treatments that use the protein folate receptor alpha or FRα to work
- •Taken any other experimental treatments
- •History of significant cardiac issues or other cancers within 3 years.
- •Significant anemia, significant neutropenia, or significant thrombocytopenia (e.g., not enough platelets in your blood - platelets held stop bleeding in your body)
- •Detectable viral load for HIV (human immunodeficiency virus), hepatitis B or C.
- •If you are pregnant.
- •Part 1: Cannot have active autoimmune diseases such as rheumatoid arthritis, SLE (systemic lupus erythematosus), ulcerative colitis, Crohn's Disease, MS (multiple sclerosis), ankylosing spondylitis, thyroiditis that require treatments that suppress your immune system.
- •Part 1: if your cancer has spread to your brain.
- •Part 2: You can have cancer that has spread to your brain but there are exceptions. The cancer in your brain cannot be causing any symptoms, it cannot be larger than 3 cm, there can be no evidence on a scan that shows your brain tissue has shifted from its expected position inside the skull (called "herniation") or be bleeding in the skull or brain itself (called "hemorrhage").
研究组 & 干预措施
ELU001
Dose Escalation: Escalating doses of ELU001 Dose Expansion: Recommended Dose for Expansion (or RP2D)
干预措施: ELU001 (Drug)
结局指标
主要结局
Part 1 Dose Escalation: The Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors.
时间窗: 28 days
To determine the MTD and/or RP2D of ELU001 in patients with over-expressing Folate Receptor Alpha tumors. When at least 2 out of 6 patients in a given dose-level experience a dose-limiting toxicity (DLT), the dose is considered to have exceeded the MTD. The MTD, therefore, is defined as the previous highest tested dose of ELU001 that did not cause a DLT in the first cycle of treatment. In the event of emerging data during Part 1, the Sponsor may, in consultation with a dose-level safety review group, decide to define a recommended dose for expansion (in for Part 2) (RP2D) instead of the MTD. DLTs are defined as a treatment-emergent adverse event (TEAE) or abnormal laboratory value related to ELU001 treatment that result in a failure to meet the criteria for re-treatment.
Part 2 Dose Expansion: To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors, per RECIST v1.1.
时间窗: First dose of study drug until responses of CR or PR, assessed up to 12 months.
Percentage of Participants with confirmed objective response as assessed by the investigator and per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 CR is defined as the disappearance of all target or non-target lesions. PR is defined as at least 30 percent (%) decrease in the sum of the longest diameters (SoD) of target lesions, taking as reference the baseline SoD.
次要结局
- Part 1 Dose Escalation: To determine overall response rate (ORR) (complete response [CR] + partial response [PR]) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors, per RECIST v1.1.(First dose of study drug until responses of CR or PR, assessed up to 12 months.)
- Part 1 and Part 2: To determine Duration of Response (DOR) of ELU001 for IV infusion in patients with over-expressing Folate Receptor Alpha tumors.(Date of first response (CR or PR) until the date of disease progression or up to 12 months, whichever occurs first.)
- Part 1 and Part 2: Number of participants with adverse events as assessed by CTCAE v5.0 Safety Evaluations.(First dose of study drug up to 28 days after the last dose of study drug or up to 12 months, whichever occurs first.)