Clinical trial

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

Name

MS201512_0010

Description

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.

Trial arms

Trial start

2021-05-24

Estimated PCD

2023-03-31

Trial end

2023-03-31

Status

Completed

Phase

Early phase I

Treatment

M4076

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

Arms:

Experimental: Dose Escalation Cohort (Part 1A): M4076 Monotherapy, Experimental: Preliminary Food Effect Assessment Cohort (Part 1B): M4076

Size

Primary endpoint

Part 1A: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period

Day 1 up to Day 21

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)

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)

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)

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)

Eligibility criteria

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

Protocol

{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE1'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 30, 'type': 'ACTUAL'}}

Updated at

2023-07-20

1 organization

1 product

1 indication

Organization

EMD Serono Research & Development Institute

Product

M4076

Indication

Cancer