Phase 1
Completed N=22
First-in-human Study of M4076 in Advanced Solid Tumors (DDRiver Solid Tumors 410)
Advanced Solid Tumors
Source: ClinicalTrials.gov NCT04882917 ↗
Enrolled (actual)
22
Serious AEs
40.9%
Results posted
Mar 2025
Primary outcomePrimary: Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 — 0; 1; 1; 2 Participants
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants Who Experienced Dose Limiting Toxicities (DLTs) Assessed Using National Cancer Institute (NCI) Common Toxicity Criteria for Adverse Events (CTCAE) Version 5.0 |
0; 1; 1; 2 | — |
| PRIMARY Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment Related TEAEs |
2; 7; 9; 4; 1; 2 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Vital Signs |
0; 0; 0; 0 | — |
| PRIMARY Number of Participants With Change From Baseline in Laboratory Test Abnormalities to Grade 3 or Higher Severity Based on NCI-CTCAE Version 5.0 |
0; 0; 0; 1; 0; 0 | — |
| PRIMARY Number of Participants With Clinically Significant Changes From Baseline in Electrocardiogram (ECG) Values |
0; 0; 0; 0 | — |
| SECONDARY Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator |
0; 0; 0; 0 | — |
| SECONDARY Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator |
— | — |
| SECONDARY Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) Assessed by Investigators |
NA; 1.1; 1.3; NA | — |
| SECONDARY Area Under the Plasma Concentration-Time Curve From Time Zero to Last Sampling Time (AUClast) of M4076 |
NA; 37000; 50500; 76600; NA; 36500 | — |
| SECONDARY Area Under Plasma Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of M4076 |
NA; 39200; 44900; 69800 | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) of M4076 |
NA; 4080; 6270; 8510; NA; 4690 | — |
| SECONDARY Absolute Changes From Baseline in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: p-ATM |
— | — |
| SECONDARY Absolute Changes From Baseline in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: p-CHK2 |
— | — |
| SECONDARY Relative Changes From Baseline in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: p-ATM |
— | — |
| SECONDARY Relative Changes From Baseline in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: p-CHK2 |
— | — |
| SECONDARY Absolute Values in Ataxia-Telangiectasia Mutated (ATM) Pathway Readouts Assessed by Flow Cytometry and Immunohistochemistry: Gamma-H2AX |
1316; 1037; 3127; 1612; 347; 1925 | — |
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:
- Active infection (i.e., requiring systemic antibiotics or antifungals)
- Uncontrolled arterial hypertension
- Severe cardiac arrhythmia requiring medication
- 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
Data sourced from ClinicalTrials.gov (NCT04882917). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.