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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT06898450




Registration number
NCT06898450
Ethics application status
Date submitted
10/03/2025
Date registered
27/03/2025
Date last updated
3/08/2025

Titles & IDs
Public title
A Study to Assess the Safety, Tolerability, and Efficacy of NDI-219216 in Patients With Advanced Solid Tumors.
Scientific 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
Secondary ID [1] 0 0
9216-101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Solid Tumors Cancer 0 0
MSI-H Cancer 0 0
Condition category
Condition code
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - NDI-219216

Experimental: 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.

Experimental: 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.

Experimental: 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.


Treatment: Drugs: NDI-219216
NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Part A Primary Objective: Incidence of dose limiting toxicities (DLTs)
Timepoint [1] 0 0
The first 21 days of Cycle 1 (Cycle 1 is 28 days).
Primary outcome [2] 0 0
Part A Primary Outcome: • Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), according to NCI CTCAE v5.0
Timepoint [2] 0 0
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.
Primary outcome [3] 0 0
Part A Primary Outcome: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) as assessed by the Investigator
Timepoint [3] 0 0
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.
Primary outcome [4] 0 0
Part B Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
Timepoint [4] 0 0
From start of study treatment until end of follow-up, up to approximately 18 months. Each Cycle is 28 days.
Primary outcome [5] 0 0
Part B Primary Outcome: Duration of Response (DOR) per RECIST v1.1
Timepoint [5] 0 0
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.
Primary outcome [6] 0 0
Part B Primary Outcome: Incidence and severity of AEs according to NCI CTCAE v5.0.
Timepoint [6] 0 0
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.
Primary outcome [7] 0 0
Part C Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.
Timepoint [7] 0 0
From start of study treatment until end of follow-up, up to approximately 17 months. Each Cycle is 28 days.
Primary outcome [8] 0 0
Part C Primary Outcome: Duration of Response (DOR) per RECIST v1.1.
Timepoint [8] 0 0
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 [1] 0 0
Part A Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
Part A Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
Part A Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
Timepoint [3] 0 0
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.
Secondary outcome [4] 0 0
Part A Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Part B Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
Timepoint [5] 0 0
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.
Secondary outcome [6] 0 0
Part B Secondary Outcome: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
Timepoint [6] 0 0
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.
Secondary outcome [7] 0 0
Part B Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
Timepoint [7] 0 0
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.
Secondary outcome [8] 0 0
Part B Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
Timepoint [8] 0 0
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.
Secondary outcome [9] 0 0
Part C Secondary Objective: Incidence and severity of AEs according to NCI CTCAE v5.0.
Timepoint [9] 0 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.
Secondary outcome [10] 0 0
Part C Secondary Objective: Plasma concentrations of NDI-219216 will be measured using a validated liquid chromatography-tandem mass spectrometry (LC-MS) assay.
Timepoint [10] 0 0
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.
Secondary outcome [11] 0 0
Part C Secondary Objective: Maximum Plasma Concentration Observed (Cmax) of NDI-219216
Timepoint [11] 0 0
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.
Secondary outcome [12] 0 0
Part C Secondary Outcome: Time of Maximum Plasma Concentration Observed (Tmax) of NDI-219216
Timepoint [12] 0 0
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.
Secondary outcome [13] 0 0
Part C Secondary Outcome: Area Under the Plasma Concentration-Time Curve (AUC0-last) of NDI-219216
Timepoint [13] 0 0
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
Key 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).
Minimum age
18 Years
Maximum age
99 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Clinically significant cardiovascular disease.
* Patients with known WRN syndrome.
* Pregnancy, breastfeeding, or intention of becoming pregnant during the study.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA
Recruitment hospital [1] 0 0
Liverpool Hospital - Liverpool
Recruitment hospital [2] 0 0
Southern Oncology Clinical Research Unit - Bedford Park
Recruitment postcode(s) [1] 0 0
2170 - Liverpool
Recruitment postcode(s) [2] 0 0
5042 - Bedford Park
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Kentucky
Country [4] 0 0
United States of America
State/province [4] 0 0
New York
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
United States of America
State/province [6] 0 0
Rhode Island
Country [7] 0 0
United States of America
State/province [7] 0 0
South Carolina
Country [8] 0 0
United States of America
State/province [8] 0 0
Virginia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Nimbus Wadjet, Inc.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Worldwide Clinical Trials
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Anita Scheuber, MD, PhD
Address 0 0
Nimbus Therapeutics, Inc.
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Sean Rossi
Address 0 0
Country 0 0
Phone 0 0
857-600-8779
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Undecided
No/undecided IPD sharing reason/comment
It is not yet known if there will be a plan to make IPD available.


What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

No documents have been uploaded by study researchers.