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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Advanced Solid Tumors Cancer; MSI-H Cancer
• Intervention / Treatment: Drug: NDI-219216

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.

• Study Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Sean Rossi; Phone Number: 857-600-8779; Email: sean.rossi@nimbustx.com
• Study Contact Backup: Name: Katie Ard, MSN; Phone Number: 303-646-7297; Email: katie.ard@nimbustx.com

Study Locations

• Australia
  • New South Wales
    • Liverpool, New South Wales, Australia, 2170
      • Recruiting
      • Liverpool Hospital
      • Principal Investigator: Aflah Roohullah, MD; PHD
  • South Australia
    • Bedford Park, South Australia, Australia, 5042
      • Recruiting
      • Southern Oncology Clinical Research Unit
      • Principal Investigator: Ganessan Kichenadasse, MD; PHD
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G2C4
      • Recruiting
      • Princess Margaret Cancer Center
      • Principal Investigator: Eric Chen, MD; PHD
• France
  • Paris, France, 75012
    • Recruiting
    • Hôpital Saint-Antoine - Assistance Publique-Hopitaux de Paris (AP-HP)
    • Principal Investigator: Thierry Andre, MD
  • Poitiers, France, 86021
    • Recruiting
    • Centre Hospitalier Universitaire (CHU) de Poitiers
    • Principal Investigator: David TOUGERON, MD
• Ireland
  • Dublin, Ireland, D07 R2WY
    • Recruiting
    • START Dublin
    • Principal Investigator: Austin Duffy, MD
• Portugal
  • Lisbon, Portugal, 1649-028
    • Recruiting
    • START Lisbon
    • Principal Investigator: Andre Mansinho, MD
• Spain
  • Barcelona, Spain, 08023
    • Recruiting
    • START Barcelona
    • Principal Investigator: Roberto Martin Huertas, MD
  • Madrid, Spain, 28040
    • Recruiting
    • Hospital Clinico San Carlos
    • Principal Investigator: Jorge Bartolome, MD
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
    • Principal Investigator: Elisa Fontana, MD
  • Manchester, United Kingdom, M20 4BX
    • Recruiting
    • The Christie Nhs Foundation Trust Uk
    • Principal Investigator: Donna Graham, MD
• United States
  • California
    • Los Angeles, California, United States, 90089
      • Recruiting
      • USC Norris Comprehensive Cancer Center
      • Principal Investigator: Josef Lenz, MD; FACP
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medicine
      • Principal Investigator: John Moroney, MD
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • Recruiting
      • University of Louisville James Graham Brown Cancer Center
      • Principal Investigator: Rebecca Redman, MD
  • New York
    • Ithaca, New York, United States, 14850
      • Terminated
      • Cayuga Cancer Center
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Recruiting
      • Levine Cancer Center
      • Principal Investigator: R. Wendel Naumann, MD
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Atrium Health Wake Forest Baptist Center
      • Principal Investigator: R. Wendel Naumann, MD
  • Ohio
    • Maumee, Ohio, United States, 43537
      • Recruiting
      • Taylor Cancer Research Center
      • Principal Investigator: John Nemunaitis, MD
  • Rhode Island
    • Providence, Rhode Island, United States, 02901
      • Recruiting
      • Brown University Health
      • Principal Investigator: Benedito Carneiro Filho, MD; MS; PhD
  • South Carolina
    • Greenville, South Carolina, United States, 29605
      • Recruiting
      • Prisma Health Cancer Institute - Multidisciplinary Center
      • Principal Investigator: William Edenfield, MD
  • Virginia
    • Charlottesville, Virginia, United States, 22908
      • Recruiting
      • University of Virginia Emily Couric Clinical Cancer Center
      • Principal Investigator: Matthew Reilley, MD
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • Virginia Cancer Specialists, P.C. - Fairfax
      • Principal Investigator: Alexander Spira, MD;PhD;FACP

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: NDI-219216; NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.
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.	Drug: NDI-219216; NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.
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.	Drug: NDI-219216; NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part B Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.		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		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 C Primary Objective: Overall Response Rate (ORR) per RECIST v1.1.		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.		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.
Part A Primary Objective: Incidence of dose limiting toxicities (DLTs)	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)	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	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.	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	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).	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 Outcome: Incidence and severity of AEs according to NCI CTCAE v5.0.	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).	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.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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: 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.
Part C Secondary Objective: Incidence and severity of AEs according to NCI CTCAE v5.0.	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).	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.

Collaborators and Investigators

• Sponsor: Nimbus Wadjet, Inc.
• Collaborators: Worldwide Clinical Trials
• Investigators: Study Director: Anita Scheuber, MD, PhD, Nimbus Therapeutics, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): March 31, 2025
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): December 1, 2031

Study Registration Dates

• First Submitted: March 10, 2025
• First Submitted That Met QC Criteria: March 25, 2025
• First Posted (Actual): March 27, 2025

Study Record Updates

• Last Update Posted (Actual): May 6, 2026
• Last Update Submitted That Met QC Criteria: May 4, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; Microsatellite Instability; Deficient Mismatch Repair; Werner syndrome helicase
• Additional Relevant MeSH Terms: Pathologic Processes; Genetic Diseases, Inborn; Metabolic Diseases; DNA Repair-Deficiency Disorders; Genomic Instability; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Nutritional and Metabolic Diseases; Microsatellite Instability; Werner Syndrome
• Other Study ID Numbers: 9216-101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: It is not yet known if there will be a plan to make IPD available.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No