A Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Antitumor Activity of NDI-219216 in Patients With Advanced Solid Tumors With/Without Microsatellite Instability and/or Deficient Mismatch Repair
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 134
- 试验地点
- 32
- 主要终点
- Part A Primary Objective: Incidence of dose limiting toxicities (DLTs)
研究概览
简要总结
The goal of this clinical trial is to learn if NDI-219216 is safe for patients, and if NDI-219216 might be a possible treatment for advanced solid tumors in the later phases of the study.
The main questions it aims to answer are:
Is NDI-219216 safe and what kinds of side effects might it cause? What kind of effects does NDI-219216 have on the body? Does NDI-219216 have any impact on tumor size?
Participants will:
Take NDI-219216 every day by mouth. Visit the clinic 6 times during Cycle 1, 2 times during Cycle 2, once a month thereafter for checkups and tests while on the study, then one time for an end of treatment visit. After the End of Study, a follow up will occur but can be done on the phone.
Keep a diary of their tablet consumption and symptoms experienced.
详细描述
Study 9216-101 is a first-in-human (FIH), Phase 1/2, open-label, dose escalation, dose optimization, and dose expansion study to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary antitumor activity of NDI-219216 in patients with advanced solid tumors.
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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1
- •Have unresectable and/or metastatic solid tumors (with or without MSI-H/dMMR) refractory to or intolerant to previous SoC therapy or for which no SoC therapy exists
- •Presence of measurable disease according to RECIST version 1.1 except for Part A (Dose Escalation)
- •Adequate bone marrow / hematologic, end-organ, and cardiovascular function
- •Resolution of all acute (or toxic) adverse effects of prior therapies, radiation therapy, or surgical procedures to Grade ≤ 1 (except fatigue, alopecia, and peripheral neuropathy).
排除标准
- •Clinically significant cardiovascular disease.
- •Patients with known WRN syndrome.
- •Pregnancy, breastfeeding, or intention of becoming pregnant during the study.
研究组 & 干预措施
Part A dose escalation
Part A Dose Escalation will involve enrolling sequential cohorts with increasing doses of NDI-219216 administered daily in repeating 28-day treatment cycles. The Dose Limiting Toxicity review period for each cohort will be 21 days for each patient enrolled, with review by a Safety Review Committee prior to escalation to the next dose level.
干预措施: NDI-219216 (Drug)
Part B Project Optimus
Part B will enroll up to 3 cohorts of patients randomized between up to 3 dose levels determined from Part A Dose Escalation. NDI-219216 will be administered daily in repeating 28-day treatment cycles.
干预措施: NDI-219216 (Drug)
Part C Dose Expansion
Part C will enroll 2 groups of patients with dMMR/MSI-h status and other select criteria, utilizing the optimal dose identified from Part B. NDI-219216 will be administered daily in 28-day repeating cycles.
干预措施: NDI-219216 (Drug)
结局指标
主要结局
Part A Primary Objective: Incidence of dose limiting toxicities (DLTs)
时间窗: The first 21 days of Cycle 1 (Cycle 1 is 28 days).
Assessments will include electrocardiograms (ECGs), echocardiogram, cardiac biomarker troponin I, physical examination, vital signs (including blood pressure, pulse), and evaluation of laboratory parameters (clinical chemistry, hematology, and coagulation)
Part A Primary Outcome: • Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), according to NCI CTCAE v5.0
时间窗: From first dose of study drug until 30 days after last dose of study drug; up to approximately 11-12 months. Each Cycle is 28 days.
Assessments will include standard electrocardiograms (ECGs), echocardiogram, cardiac biomarker troponin I, physical examination, vital signs (including blood pressure, pulse), and evaluation of laboratory parameters (clinical chemistry, hematology, and coagulation.
Part A Primary Outcome: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) as assessed by the Investigator
时间窗: From first dose of study drug until 30 days after last dose of study drug; up to approximately 11-12 months. Each Cycle is 28 days.
Assessments will include standard electrocardiograms (ECGs), echocardiogram, cardiac biomarker troponin I, physical examination, vital signs (including blood pressure, pulse), and evaluation of laboratory parameters (clinical chemistry, hematology, and coagulation).
Part B Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
时间窗: From start of study treatment until end of follow-up, up to approximately 18 months. Each Cycle is 28 days.
Part B Primary Outcome: Duration of Response (DOR) per RECIST v1.1
时间窗: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first; up to approximately 18 months. Each Cycle is 28 days.
Part B Primary Outcome: Incidence and severity of AEs according to NCI CTCAE v5.0.
时间窗: From first dose of study drug until 30 days after last dose of study drug; up to approximately 18 months. Each Cycle is 28 days.
Assessments will include standard electrocardiograms (ECGs), echocardiogram, cardiac biomarker troponin I, physical examination, vital signs (including blood pressure, pulse), and evaluation of laboratory parameters (clinical chemistry, hematology, and coagulation).
Part C Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
时间窗: From start of study treatment until end of follow-up, up to approximately 17 months. Each Cycle is 28 days.
Part C Primary Outcome: Duration of Response (DOR) per RECIST v1.1.
时间窗: From the time of first occurrence of a documented response until the time of documented disease progression or death from any cause, whichever occurs first, up to approximately 17 months. Each Cycle is 28 days.
次要结局
- Part A Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part A Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part A Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part A Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1 from time zero to the last observable concentration. Cycle 1 is 28 days in length.)
- Part B Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part B Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part B Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part B Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1 from time zero to the last observable concentration. Cycle 1 is 28 days in length.)
- Part C Secondary Objective: Incidence and severity of AEs according to NCI CTCAE v5.0.(From first dose of study drug until 30 days after last dose of study drug; up to approximately 17 months. Each Cycle is 28 days.)
- Part C Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part C Secondary Objective: Maximum Plasma Concentration Observed (Cmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part C Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)
- Part C Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216(At pre-specified timepoints on Day 1, Day 2, Day 8, Day 21, and Day 22 of Cycle 1. Cycle 1 is 28 days in length.)