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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Advanced Solid Tumors

Treatments: Drug: M4076

Study type: Interventional

Funder types: Industry

Identifiers

NCT04882917

MS201512_0010

Details and patient eligibility

About

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.

Enrollment: 22 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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22 participants in 4 patient groups

Part 1A Dose Escalation: M4076 100 mg

Experimental group

Description:

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

Treatment:

Drug: M4076

Part 1A Dose Escalation: M4076 200 mg

Experimental group

Description:

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.

Treatment:

Drug: M4076

Part 1A Dose Escalation: M4076 300 mg

Experimental group

Description:

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.

Treatment:

Drug: M4076

Part 1A Dose Escalation: M4076 400 mg

Experimental group

Description:

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.

Treatment:

Drug: M4076