Phase 1
N=58
First in Human Study of M6223
Metastatic Solid Tumors
Bottom Line
View on ClinicalTrials.gov: NCT04457778 ↗Enrolled (actual)
58
Serious AEs
37.9%
Results posted
May 2026
Primary outcome: Primary: Part 1A and 1B: 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; 0; 0; 0 Participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 1
- Interventions
- M6223 (Drug); Bintrafusp alfa (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- EMD Serono Research & Development Institute, Inc.
- Primary completion
- Jun 2023
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1A and 1B: 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; 0; 0; 0; 1; 0 | — |
| PRIMARY Part 1A and 1B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs |
1; 1; 3; 3; 9; 11 | — |
| PRIMARY Part 1A and 1B: Number of Participants With TEAES With Severity of Grade Greater or Equal to 3 and TEAEs Leading to Deaths |
0; 0; 1; 1; 4; 4 | — |
| PRIMARY Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values |
0; 0; 1; 1; 2; 3 | — |
| PRIMARY Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG) |
0; 0; 0; 0; 0; 0 | — |
| PRIMARY Part 1A and 1B: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs |
0; 0; 0; 0; 0; 2 | — |
| PRIMARY Part 1A and 1B: Number of Participants With Worsened Post Baseline Shift in Eastern Cooperative Oncology Group Performance Status |
0; 0; 1; 1; 3; 3 | — |
| SECONDARY Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC 0-t) of M6223 |
NA; NA; 2950; 9640; 30100; 50000 | — |
| SECONDARY Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223 |
NA; NA; 4000; 13800; 37400; 76600 | — |
| SECONDARY Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (AUC-tau) of M6223 |
NA; NA; 2950; 9600; 28100; 50100 | — |
| SECONDARY Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223 |
2.01; 6.83; 20.9; 65.5; 217; 329 | — |
| SECONDARY Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223 |
2.01; 6.83; 20.9; 65.5; 217; 329 | — |
| SECONDARY Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223 |
1.57; 4.08; 1.50; 1.12; 1.28; 1.25 | — |
| SECONDARY Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223 |
NA; NA; 144; 182; 166; 216 | — |
| SECONDARY Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223 |
NA; NA; 0.00618; 0.00433; 0.00433; 0.00340 | — |
| SECONDARY Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa |
420; 353; 387 | — |
| SECONDARY Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp Alfa |
62.8; 74.9; 61.6 | — |
| SECONDARY Part IA and 1B: Number of Participants With Positive Antidrug Antibody (ADA) Assays |
1; 1; 1; 1; 0; 0 | — |
| SECONDARY Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Part 1A and 1B: Duration of Response (DOR) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator |
— | — |
| SECONDARY Part 1A and 1B: Time to Tumor Response (TTR) According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator |
— | — |
| SECONDARY Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator |
0; 0; 0; 33.33; 0; 0 | — |
| SECONDARY Part 1A and 1B: Progression-free Survival Time According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as Per Investigator |
1.7; 1.3 | — |
| SECONDARY Part 1A and 1B: Overall Survival |
7.6; 5.8 | — |
Summary
The main purpose of this study was to determine the safety, tolerability, pharmacokinetics (PK), immunogenicity and (if observed) the maximum tolerated dose (MTD) of M6223 as a single agent (Part 1A) for both the every 2 weeks (Q2W) regimen and the every 3 weeks (Q3W) regimen and of M6223 combined with bintrafusp alfa (Part 1B) for Q2W regimen in participants with metastatic or locally advanced solid unresectable tumors.
Eligibility Criteria
Inclusion Criteria
- Participants have histologically or cytologically proven locally advanced or advanced solid malignancies who are refractory to or have progressed under standard treatment and have no other treatment options known to confer clinical benefit
- Participants with Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at Screening
- Participant has a formalin-fixed paraffin-embedded block containing tumor tissue or a minimum of 15 (preferably 25) unstained tumor slides suitable for immunohistochemistry-based staining of protein expression
- Participants with life expectancy of at least 12 weeks
- Participants with measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)
- Adequate hematological, hepatic and renal function as defined in the protocol
- Other protocol defined inclusion criteria may apply
Exclusion Criteria
- Participants with persisting toxicity related to prior therapy Grade greater than (>) 1 National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0, however, alopecia, sensory neuropathy Grade less than or equal to ( =) 3 NCI-CTCAE Version 5.0 unless resolved to Grade 450 milli seconds (ms) on triplicate 12-lead ECG or impaired cardiovascular function, ventricular tachycardia, hypokalemia or a history of paroxysmal atrial fibrillation, serious cardiac arrhythmia and family history of sudden death or long QT syndrome
- A history of vascular, cardiovascular or cerebrovascular disease like, cerebral vascular accident/stroke (less than [ = II), deep vein thrombosis (< 3 months prior to enrollment) or pulmonary thrombosis/embolism (< 3 months prior to enrollment)
- Other protocol defined exclusion criteria may apply
Data sourced from ClinicalTrials.gov (NCT04457778). 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.