NDI-219216 for Cancer

Recruiting at 19 trial locations

Overseen By Katie Ard, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Nimbus Wadjet, Inc.

Disqualifiers: Cardiovascular disease, WRN syndrome, pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

134 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called NDI-219216 to determine its safety and effectiveness for individuals with advanced solid tumors. Researchers aim to assess whether the treatment can shrink tumors and identify any potential side effects. Participants will take a daily tablet and attend regular clinic checkups. The trial seeks individuals with solid tumors that cannot be removed or have spread, and who have not had success with other treatments. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that NDI-219216 is likely to be safe for humans?

Research has shown that NDI-219216 has been tested for safety in people with advanced solid tumors. It targets a specific protein that aids in cell repair. Studies have found that even at low doses, it can significantly shrink tumors and, in some cases, completely eliminate them, which is promising.

However, since this is an early-stage trial, researchers are still collecting detailed safety information in humans. This phase mainly focuses on understanding the treatment's safety. It often involves testing different doses to find the safest one with the fewest side effects.

Participants will take the treatment orally every day and visit the clinic regularly for checkups and tests. They will also keep a diary of their symptoms and how they feel. This helps researchers learn more about any side effects the treatment might cause.

In summary, while early results are promising, ongoing trials will provide more detailed information on how well participants tolerate NDI-219216. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about NDI-219216 for cancer treatment because it offers a fresh approach by potentially targeting cancers with DNA mismatch repair deficiency (dMMR) and microsatellite instability-high (MSI-h) status, conditions not always effectively addressed by current options like chemotherapy and immunotherapy. While most treatments focus on broad-spectrum cancer cells, NDI-219216 aims to work on specific genetic markers, potentially leading to more precise and effective outcomes. Additionally, its regimen of daily oral administration in 28-day cycles could offer more convenience compared to traditional intravenous therapies, potentially improving patient adherence and quality of life.

What evidence suggests that NDI-219216 might be an effective treatment for advanced solid tumors?

Research has shown that NDI-219216 could be a promising treatment for advanced solid tumors. Early results indicate that it effectively targets a specific protein, leading to significant tumor shrinkage. In lab studies, NDI-219216 outperformed similar treatments, particularly for MSI-H tumors, which usually resist standard therapies. This trial will explore NDI-219216 across different treatment arms, including dose escalation and dose expansion phases, to determine its optimal dosing and effectiveness. These initial findings suggest that NDI-219216 might reduce tumor size and maintain its effects over time. However, more research is needed to confirm its effectiveness in people. ^{1 6 7 8 9}

Who Is on the Research Team?

Anita Scheuber, MD, PhD

Principal Investigator

Nimbus Therapeutics, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with advanced solid tumors, particularly those showing microsatellite instability. Participants must be able to take oral medication daily and commit to regular clinic visits for checkups and tests.

Inclusion Criteria

My cancer cannot be removed by surgery and has not responded to or I cannot tolerate standard treatments.

I am fully active or can carry out light work.

Presence of measurable disease according to RECIST version 1.1 except for Part A (Dose Escalation)

Exclusion Criteria

I have a serious heart condition.

I have been diagnosed with Werner syndrome.

Pregnancy, breastfeeding, or intention of becoming pregnant during the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment - Part A Dose Escalation

Participants receive increasing doses of NDI-219216 daily in 28-day treatment cycles. Dose Limiting Toxicity review period is 21 days for each cohort.

Up to 11-12 months

6 visits during Cycle 1, 2 visits during Cycle 2, monthly thereafter

Treatment - Part B Project Optimus

Participants are randomized between up to 3 dose levels determined from Part A, administered daily in 28-day treatment cycles.

Up to 18 months

Treatment - Part C Dose Expansion

Participants with dMMR/MSI-h status receive the optimal dose identified from Part B, administered daily in 28-day treatment cycles.

Up to 17 months

Follow-up

Participants are monitored for safety and effectiveness after treatment. Follow-up can be done on the phone.

30 days after last dose

What Are the Treatments Tested in This Trial?

Interventions

• NDI-219216

Trial Overview The study is testing the safety and effectiveness of a new treatment called NDI-219216. Patients will take it orally every day, aiming to see if it's safe, its side effects, how it affects the body, and whether it can reduce tumor size.

How Is the Trial Designed?

Group I: Part C Dose Expansion Experimental Treatment 1 Intervention

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.

Group II: Part B Project Optimus Experimental Treatment 1 Intervention

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.

Group III: Part A dose escalation Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Nimbus Wadjet, Inc.

Lead Sponsor

Trials

1

Recruited

130+

Worldwide Clinical Trials

Collaborator

Trials

70

Recruited

15,800+

Published Research Related to This Trial

The maximum-tolerated dose (MTD) of cediranib in children with recurrent CNS tumors was initially set at 32 mg/m²/day, but excessive toxicities led to concerns about its long-term tolerability.

At a lower dose of 20 mg/m²/day, cediranib still showed poor tolerability, indicating that both doses may not be suitable for extended treatment in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I trial and PK study of cediranib (AZD2171), an orally bioavailable pan-VEGFR inhibitor, in children with recurrent or refractory primary CNS tumors. Kieran, MW., Chi, S., Goldman, S., et al.[2018]

Cediranib, when combined with standard chemotherapy (cisplatin and gemcitabine), showed promising anti-tumor activity in advanced non-small cell lung cancer, with a response rate of 26.7% among all patients and 33.3% among those evaluable.

The study found that cediranib can be safely administered at a daily dose of 30 mg without dose-limiting toxicities, although some manageable side effects like fatigue and diarrhea were noted, indicating its potential for further development in phase III trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I and pharmacokinetic study of daily oral cediranib, an inhibitor of vascular endothelial growth factor tyrosine kinases, in combination with cisplatin and gemcitabine in patients with advanced non-small cell lung cancer: a study of the National Cancer Institute of Canada Clinical Trials Group. Goss, G., Shepherd, FA., Laurie, S., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06898450

NCT06898450 | A Study to Assess the Safety, Tolerability, ... 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 ...

2. nimbustx.com nimbustx.com/jobs/5097630004/

First participants dosed in Phase 1/2 clinical trial The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses ...

3. nimbustx.com nimbustx.com/wp-content/uploads/POSTER-Nimbus_AACR_2025.pdf

NDI-219216: A Non-Covalent, Potent, Selective and Highly ... NDI-219216 outperformed existing clinical stage WRN inhibitors (Novartis HRO761,. Roche RO7589831) across multiple MSI-H preclinical models (Fig ...

4. trial.medpath.com trial.medpath.com/news/7db1d21d9342af9b/nimbus-therapeutics-initiates-first-in-human-trial-of-ndi-219216-for-msi-h-tumors-resistant-to-standard-therapies

Nimbus Therapeutics Initiates First-in-Human Trial of NDI ... Preclinical data demonstrate NDI-219216's superior efficacy against MSI-H tumors compared to other clinical-stage WRN inhibitors, with ...

5. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06898450/a-study-to-assess-the-safety-tolerability-and-efficacy-of-ndi-219216-in-patients-with-advanced-solid-tumors

A Study to Assess the Safety, Tolerability, and Efficacy of ... 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.

6. nimbustx.com nimbustx.com/2025/04/25/nimbus-therapeutics-announces-initiation-of-first-in-human-clinical-trial-with-ndi-219216-novel-wrn-inhibitor-for-msi-h-tumors/

Nimbus Therapeutics Announces Initiation of First-in- ... The data demonstrate that NDI-219216 is a potent and selective WRN inhibitor with significant tumor regression and sustained complete responses ...

7. annalsofoncology.org annalsofoncology.org/article/S0923-7534(25)02518-9/fulltext

1029eTiP A phase I/II open-label study of NDI-219216, ... This first-in-human study evaluates the safety, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of NDI-219216 in advanced solid tumors, ...

8. nimbustx.com nimbustx.com/2025/01/09/nimbus-therapeutics-announces-clinical-progress-in-oncology-therapeutic-pipeline-and-provides-business-updates/

Nimbus Therapeutics Announces Clinical Progress in ... Tummino. “NDI-219216 has demonstrated compelling preclinical data, including significant tumor regression and complete responses at low oral ...

9. ctv.veeva.com ctv.veeva.com/study/a-study-to-assess-the-safety-tolerability-and-efficacy-of-ndi-219216-in-patients-with-advanced-sol

A Study to Assess the Safety, Tolerability, and Efficacy of NDI ... 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 ...