A Study to Assess the Safety, Tolerability, and Efficacy of NDI-219216 in Patients With Advanced Solid Tumors.

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат NDI-219216
  NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.

Первичные конечные точки

• Part A Primary Objective: Incidence of dose limiting toxicities (DLTs) [Срок оценки: The first 21 days of Cycle 1 (Cycle 1 is 28 days).]
• Part A Primary Outcome: • Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), according to NCI CTCAE v5.0 [Срок оценки: 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.]
• Part A Primary Outcome: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) as assessed by the Investigator [Срок оценки: 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.]
• Part B Primary Objective: Overall Response Rate (ORR) per RECIST v1.1. [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: 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.]
• Part C Primary Objective: Overall Response Rate (ORR) per RECIST v1.1. [Срок оценки: 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. [Срок оценки: 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.]

Вторичные конечные точки (12)

• Part A Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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. [Срок оценки: 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. [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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.]

Критерии участия

Критерии включения

• 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).

Критерии исключения

• Clinically significant cardiovascular disease.
• Patients with known WRN syndrome.
• Pregnancy, breastfeeding, or intention of becoming pregnant during the study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Последовательный дизайн

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 11 центров

• USC Norris Comprehensive Cancer Center — Los Angeles
• University of Chicago Medicine — Chicago
• University of Louisville James Graham Brown Cancer Center — Louisville
• Cayuga Cancer Center — Ithaca
• Levine Cancer Center — Charlotte
• Atrium Health Wake Forest Baptist Center — Winston-Salem
• Taylor Cancer Research Center — Maumee
• Brown University Health — Providence
• … и ещё 3 центра

Австралия · 2 центра

• Liverpool Hospital — Liverpool
• Southern Oncology Clinical Research Unit — Bedford Park

Франция · 2 центра

• Hôpital Saint-Antoine - Assistance Publique-Hopitaux de Paris (AP-HP) — Paris
• Centre Hospitalier Universitaire (CHU) de Poitiers — Poitiers

Испания · 2 центра

• START Barcelona — Barcelona
• Hospital Clinico San Carlos — Madrid

Великобритания · 2 центра

• Sarah Cannon Research Institute UK — London
• The Christie NHS Foundation Trust UK — Manchester

Канада · 1 центр

• Princess Margaret Cancer Center — Toronto

Ирландия · 1 центр

• START Dublin — Dublin

Португалия · 1 центр

• START Lisbon — Lisbon

Идентификаторы

NCT: NCT06898450 · 9216-101

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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