First-in-human Study of M4076 in Advanced Solid Tumors (DDRiver Solid Tumors 410)

Advanced Solid Tumors Clinical Trial

Official title:

A First-in-human, Phase I, Open-label Study of the ATM Inhibitor M4076 in Participants With Advanced Solid Tumors (DDRiver Solid Tumors 410)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04882917
• Other study ID #: MS201512_0010
• Status: Completed
• Phase: Phase 1
• 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
• 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

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Neoplasms

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

External Links

•   DDRiver website
•   Trial Awareness and Transparency website
•   US Medical Information website, Medical Resources