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

NCT06898450 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 9216-101
• Study Type: interventional
• Target: 134
• Locations: 8 countries
• Sites: 22

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.

Conditions

MSI-H Cancer; Advanced Solid Tumors Cancer

Keywords

Advanced Solid Tumors; Microsatellite Instability; Deficient Mismatch Repair; Werner syndrome helicase

Outcome Measures

Primary Outcomes (8)

• 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 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 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.

• 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.

Secondary Outcomes (13)

• 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.

Study Arms (3)

Part A dose escalation

EXPERIMENTAL

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

Part B Project Optimus

EXPERIMENTAL

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

Part C Dose Expansion

EXPERIMENTAL

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

Interventions

NDI-219216 DRUG

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

Part A dose escalation; Part B Project Optimus; Part C Dose Expansion

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

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

Sponsors & Collaborators

• Nimbus Wadjet, Inc.: lead
• Worldwide Clinical Trials: collaborator

Study Sites (22)

USC Norris Comprehensive Cancer Center

Los Angeles, California, 90089, United States

RECRUITING

University of Chicago Medicine

Chicago, Illinois, 60637, United States

RECRUITING

University of Louisville James Graham Brown Cancer Center

Louisville, Kentucky, 40202, United States

RECRUITING

Cayuga Cancer Center

Ithaca, New York, 14850, United States

TERMINATED

Levine Cancer Center

Charlotte, North Carolina, 28204, United States

RECRUITING

Atrium Health Wake Forest Baptist Center

Winston-Salem, North Carolina, 27157, United States

RECRUITING

Taylor Cancer Research Center

Maumee, Ohio, 43537, United States

RECRUITING

Brown University Health

Providence, Rhode Island, 02901, United States

RECRUITING

Prisma Health Cancer Institute - Multidisciplinary Center

Greenville, South Carolina, 29605, United States

RECRUITING

University of Virginia Emily Couric Clinical Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

Virginia Cancer Specialists, P.C. - Fairfax

Fairfax, Virginia, 22031, United States

RECRUITING

Liverpool Hospital

Liverpool, New South Wales, 2170, Australia

RECRUITING

Southern Oncology Clinical Research Unit

Bedford Park, South Australia, 5042, Australia

RECRUITING

Princess Margaret Cancer Center

Toronto, Ontario, M5G2C4, Canada

RECRUITING

Hôpital Saint-Antoine - Assistance Publique-Hopitaux de Paris (AP-HP)

Paris, 75012, France

RECRUITING

Centre Hospitalier Universitaire (CHU) de Poitiers

Poitiers, 86021, France

RECRUITING

START Dublin

Dublin, D07 R2WY, Ireland

RECRUITING

START Lisbon

Lisbon, 1649-028, Portugal

RECRUITING

START Barcelona

Barcelona, 08023, Spain

RECRUITING

Hospital Clinico San Carlos

Madrid, 28040, Spain

RECRUITING

Sarah Cannon Research Institute UK

London, W1G 6AD, United Kingdom

RECRUITING

The Christie NHS Foundation Trust UK

Manchester, M20 4BX, United Kingdom

RECRUITING

MeSH Terms

Conditions

Microsatellite Instability; Werner Syndrome

Condition Hierarchy (Ancestors)

Genomic Instability; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Anita Scheuber, MD, PhD

  Nimbus Therapeutics, Inc.

  STUDY DIRECTOR

Central Study Contacts

Sean Rossi

CONTACT

857-600-8779; sean.rossi@nimbustx.com

Katie Ard, MSN

CONTACT

303-646-7297; katie.ard@nimbustx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 10, 2025
• First Posted: March 27, 2025
• Study Start: March 31, 2025
• Primary Completion (Estimated): October 1, 2031
• Study Completion (Estimated): December 1, 2031
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

AU (2); GB (2); CA (1); FR (2); US (11); IE (1); PT (1); ES (2)