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Recruiting NCT06898450

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

Phase I / Phase II Interventional Advanced Solid Tumors Cancer MSI-H Cancer

For patients and families

In plain language

An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.

What is being studied
The protocol lists: NDI-219216.
Who it may be relevant to
Registry conditions: Advanced Solid Tumors Cancer, MSI-H Cancer. Basic parameters: 18 years — 99 years · All.
What needs checking
Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
Where it takes place
United States, Australia, Canada, France, Ireland +3
Next step
Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →

Unsure about the terms? Read our patient guide →

Official title

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

Overview

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.

Detailed description

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.

Interventions

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

Primary outcome measures

  • Part A Primary Objective: Incidence of dose limiting toxicities (DLTs) [Time frame: 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 [Time frame: 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 [Time frame: 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. [Time frame: 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 [Time frame: 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. [Time frame: 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. [Time frame: 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. [Time frame: 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.]
Secondary outcome measures (12)
  • Part A Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay. [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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. [Time frame: 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 [Time frame: 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 [Time frame: 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 [Time frame: 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. [Time frame: 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. [Time frame: 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 [Time frame: 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 [Time frame: 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.]

Eligibility criteria

Inclusion criteria

  • 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).

Exclusion criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation
Non-randomized
Model
Sequential
Masking
Open label
Primary purpose
Treatment

Study locations

United States · 11 centers
  • 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
  • … and 3 more centers
Australia · 2 centers
  • Liverpool Hospital — Liverpool
  • Southern Oncology Clinical Research Unit — Bedford Park
France · 2 centers
  • Hôpital Saint-Antoine - Assistance Publique-Hopitaux de Paris (AP-HP) — Paris
  • Centre Hospitalier Universitaire (CHU) de Poitiers — Poitiers
Spain · 2 centers
  • START Barcelona — Barcelona
  • Hospital Clinico San Carlos — Madrid
United Kingdom · 2 centers
  • Sarah Cannon Research Institute UK — London
  • The Christie NHS Foundation Trust UK — Manchester
Canada · 1 center
  • Princess Margaret Cancer Center — Toronto
Ireland · 1 center
  • START Dublin — Dublin
Portugal · 1 center
  • START Lisbon — Lisbon

Identifiers

NCT: NCT06898450 · 9216-101

Primary sources (government registries)

View this study on ClinicalTrials.gov ↗