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Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT04882917
Other study ID # MS201512_0010
Secondary ID
Status Completed
Phase Phase 1
First received
Last updated
Start date May 24, 2021
Est. completion date March 31, 2023

Study information

Verified date July 2023
Source EMD Serono
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

The purpose of this study is to determine the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), maximum tolerated dose (MTD) (if reached) and early signs of efficacy of M4076 monotherapy in participants with solid tumors in dose escalation (Part 1A). Once the recommended dose for expansion (RDE) is declared in Part 1A, a preliminary food effect cohort, Part 1B, will follow at the RDE determined from Part 1A.


Recruitment information / eligibility

Status Completed
Enrollment 30
Est. completion date March 31, 2023
Est. primary completion date March 31, 2023
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - Participants with advanced solid tumors, for whom no standard of care therapy exists or for whom is not considered sufficiently effective, or who cannot tolerate standard of care - Participants with Eastern Cooperative Oncology Group Performance status 0 or 1 - Adequate hematological, hepatic, and renal function as defined in the protocol - Participants in Part 1B (the preliminary food effect assessment) must agree to provide paired tumor biopsies if not contraindicated for medical reasons - Other protocol defined inclusion criteria could apply Exclusion Criteria: - Clinically significant (i.e., active) uncontrolled intercurrent illness including, but not limited to: 1. Active infection (i.e., requiring systemic antibiotics or antifungals) 2. Uncontrolled arterial hypertension 3. Severe cardiac arrhythmia requiring medication 4. Cerebral vascular accident/stroke - Has known ataxia telangiectasia - Participants with tumors harboring previously identified ATM mutations - Participants with hypersensitivity to the active substance or to any of the excipients of M4076 - Other protocol defined exclusion criteria could apply

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
M4076
M4076 will be administered orally, in Part 1A and Part 1B.

Locations

Country Name City State
Canada Princess Margaret Cancer Centre Toronto Ontario
United States MD Anderson Center Houston Texas
United States NEXT Oncology San Antonio Texas

Sponsors (2)

Lead Sponsor Collaborator
EMD Serono Research & Development Institute, Inc. Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type Measure Description Time frame Safety issue
Primary Part 1A: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period Day 1 up to Day 21
Primary Part 1A: Occurrence of Adverse Events (AEs) and Treatment-Related AEs Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Primary Part 1A: Number of Participants With Clinical Significant Changes in Vital Signs, Laboratory Parameters, and 12-Lead Electrocardiogram (ECG) Findings Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Primary Part 1B: Occurrence of Adverse Events (AEs) and Treatment-Related AEs Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Primary Part 1B: Number of Participants With Clinical Significant Changes in Vital Signs, Laboratory Parameters, and 12-Lead Electrocardiogram (ECG) Findings Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Secondary Part 1A and Part 1B: Objective Response According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Investigators Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Secondary Part 1A and Part 1B: Duration of Response According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Investigators Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Secondary Part 1A and Part 1B: Progression Free Survival (PFS) Time According to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 as Assessed by Investigators Time from randomization to final assessment at end of safety follow-up visit (up to a maximum of approximately 1 years)
Secondary Part 1A and 1B: Area Under Plasma Concentration-Time Curve (AUC) From Time Zero (= Dosing Time) to the Last Sampling Time (tlast) of M4076 Pre-dose up to 14 months post-dose
Secondary Part 1A and Part 1B: Area Under Plasma Concentration (AUC) From Time Zero (Dosing Time) Extrapolated to Infinity (AUC0-inf) of M4076 Pre-dose up to 14 months post-dose
Secondary Part 1A and Part 1B: Maximum Observed Plasma Concentration (Cmax) of M4076 Pre-dose up to 14 months post-dose
Secondary Part 1A and Part 1B: Absolute and Relative Changes From Baseline in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry ATM pathway readouts including phosphorylated ataxia-telangiectasia mutated (p-ATM), gamma histone family member X (gamma-H2AX) and checkpoint kinase 2 protein (p-CHK2) will measure by flow cytometry and immunohistochemistry. Pre-dose up to 14 months post-dose
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