Clinical trial NCT06898450: A Study to Assess the Safety, Tolerability, and Efficacy of NDI-219216 in Patients With Advanced Solid Tumors.
Official title: A Phase 1/2 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumors Cancer
MSI-H Cancer
Keywords: Advanced Solid Tumors
Microsatellite Instability
Deficient Mismatch Repair
Werner syndrome helicase
Lead sponsor: Nimbus Therapeutics
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2025-03-27
Enrollment: 134
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Part A Primary Objective: Incidence of dose limiting toxicities (DLTs)
timeFrame: The first 21 days of Cycle 1 (Cycle 1 is 28 days).
measure: Part A Primary Outcome: • Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), according to NCI CTCAE v5.0
timeFrame: 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.
measure: Part A Primary Outcome: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) as assessed by the Investigator
timeFrame: 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.
measure: Part B Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
timeFrame: From start of study treatment until end of follow-up, up to approximately 18 months. Each Cycle is 28 days.
measure: Part B Primary Outcome: Duration of Response (DOR) per RECIST v1.1
timeFrame: 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.
measure: Part B Primary Outcome: Incidence and severity of AEs according to NCI CTCAE v5.0.
timeFrame: 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.
measure: Part C Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
timeFrame: From start of study treatment until end of follow-up, up to approximately 17 months. Each Cycle is 28 days.
measure: Part C Primary Outcome: Duration of Response (DOR) per RECIST v1.1.
timeFrame: 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 outcomes:
measure: Part A Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
timeFrame: 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.
measure: Part A Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
timeFrame: 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.
measure: Part A Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
timeFrame: 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.
measure: Part A Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
timeFrame: 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.
measure: Part B Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
timeFrame: 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.
measure: Part B Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
timeFrame: 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.
measure: Part B Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
timeFrame: 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.
measure: Part B Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
timeFrame: 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.
measure: Part C Secondary Objective: Incidence and severity of AEs according to NCI CTCAE v5.0.
timeFrame: 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.
measure: Part C Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
timeFrame: 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.
measure: Part C Secondary Objective: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
timeFrame: 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.
measure: Part C Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
timeFrame: 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.
measure: Part C Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
timeFrame: 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.
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: USC San Diego Health
state: California
city: Los Angeles
country: United States
facility: USC Norris Comprehensive Cancer Center
state: California
city: Chicago
country: United States
facility: University of Chicago Medicine
state: Illinois
city: Louisville
country: United States
facility: University of Louisville James Graham Brown Cancer Center
state: Kentucky
city: Ithaca
country: United States
facility: Cayuga Cancer Center
state: New York
city: Maumee
country: United States
facility: Taylor Cancer Research Center
state: Ohio
city: Providence
country: United States
facility: Brown University Health
state: Rhode Island
city: Greenville
country: United States
facility: Prisma Health Cancer Institute - Multidisciplinary Center
state: South Carolina
city: Nashville
country: United States
facility: Tennessee Oncology
state: Tennessee
city: Charlottesville
country: United States
facility: University of Virginia Emily Couric Clinical Cancer Center
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists, P.C. - Fairfax
state: Virginia
Study officials:
affiliation: Nimbus Therapeutics, Inc.
name: Anita Scheuber, MD, PhD
role: STUDY_DIRECTOR
References: