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

NCT ID: NCT04882917

Last Updated: 2025-03-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-05-24
• Study Completion Date: 2023-03-31

Brief Summary

The purpose of this study was 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) was declared in Part 1A, a preliminary food effect cohort, Part 1B, will follow at the RDE determined from Part 1A.

Conditions

Advanced Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A Dose Escalation: M4076 100 mg

Participants received M4076 film coated tablets at a dose of 100 milligrams (mg), orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study

Group Type: EXPERIMENTAL

M4076

Intervention Type: DRUG

M4076 was administered orally.

Part 1A Dose Escalation: M4076 200 mg

Participants received M4076 film coated tablets at a dose of 200 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.

Group Type: EXPERIMENTAL

M4076

Intervention Type: DRUG

M4076 was administered orally.

Part 1A Dose Escalation: M4076 300 mg

Participants received M4076 film coated tablets at a dose of 300 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.

Group Type: EXPERIMENTAL

M4076

Intervention Type: DRUG

M4076 was administered orally.

Part 1A Dose Escalation: M4076 400 mg

Participants received M4076 film coated tablets at a dose of 400 mg, orally once daily in 21-day cycles, starting from Day 1 of each cycle disease progression, death, AE leading to discontinuation of study intervention(s), or withdrawal of consent, whichever occurred first, or End of Study.

Group Type: EXPERIMENTAL

M4076

Intervention Type: DRUG

M4076 was administered orally.

Interventions

M4076

M4076 was administered orally.

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Locations

MD Anderson Center

Houston, Texas, United States

NEXT Oncology

San Antonio, Texas, United States

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Countries

United States; Canada

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201512_0010

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

http://www.DDRiver-trials.com

DDRiver website

Other Identifiers

MS201512_0010

Identifier Type: -

Identifier Source: org_study_id