Advanced Solid Tumors Cancer, MSI-H Cancer
Conditions
Keywords
Advanced Solid Tumors, Microsatellite Instability, Deficient Mismatch Repair, Werner syndrome helicase
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.
Interventions
DRUGNDI-219216
NDI-219216 is a highly selective small molecule inhibitor of WRN helicase activity.
Sponsors
Nimbus Wadjet, Inc.
Worldwide Clinical Trials
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 99 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Part A Primary Objective: Incidence of dose limiting toxicities (DLTs) | The first 21 days of Cycle 1 (Cycle 1 is 28 days). | 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) |
| Part A Primary Outcome: • Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), according to NCI CTCAE v5.0 | 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. | 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. |
| Part A Primary Outcome: Incidence and severity of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) as assessed by the Investigator | 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. | 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). |
| 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. | 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. | 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). |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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: Incidence and severity of AEs according to NCI CTCAE v5.0. | 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. | 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). |
| 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. | — |
Countries
Australia, Canada, France, Ireland, Portugal, Spain, United Kingdom, United States
Contacts
CONTACTSean Rossi
CONTACTKatie Ard, MSN
STUDY_DIRECTORAnita Scheuber, MD, PhD
Nimbus Therapeutics, Inc.
Outcome results
None listed