First in Human Study of M6223

NCT04457778 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: MS201430_0001
• Study Type: interventional
• Target: 58
• Locations: 2 countries
• Sites: 4

Brief 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.

Conditions

Metastatic Solid Tumors

Keywords

M6223; Bintrafusp alfa; Metastatic Solid Tumors

Outcome Measures

Primary Outcomes (7)

• 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

  A DLT is defined as any Grade ≥ 3 non-hematologic AE or any Grade ≥ 4 hematologic AE according to the NCI-CTCAE, occurring during the DLT observation period (28 days from first administration of study intervention) that is not clearly related to the underlying disease or any previous or concomitant medication, concomitant disease or unrelated illness. A DLT must be confirmed by the Safety Monitoring Committee. DLT is considered if the following related AEs occur: • Grade ≥ 3 neutropenia with clinical signs/symptoms (e.g., febrile neutropenia). • Grade ≥ 3 thrombocytopenia with medically concerning bleeding. • A study intervention-related treatment-emergent AE that in the opinion of the SMC is of potential clinical significance such that further dose escalation would expose participants to unacceptable risk. • Grade ≥ 3 hematological AE with symptoms that require growth factor support or transfusion to prevent further damage to the participant.

  Day 1 to Day 28

• Part 1A and 1B: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs

  An adverse event (AE) is defined as any untoward medical occurrence in a participant or clinical study participant, temporally associated with the use of study intervention, whether considered related to the study intervention or not. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs were defined as events that started or worsened after first dose of study intervention until 30 days after last dose. TEAEs included both serious and non-serious TEAEs. Treatment-related TEAEs is defined as reasonably related to the study intervention.

  Approximately 2 years 11 months

• Part 1A and 1B: Number of Participants With TEAES With Severity of Grade Greater or Equal to 3 and TEAEs Leading to Deaths

  An adverse event (AE) is any untoward medical occurrence in a participant temporally associated with the use of the study intervention, regardless of causality. A serious AE results in death, is life-threatening, requires/prolongs hospitalization, causes disability/incapacity, leads to a congenital anomaly/birth defect, or is otherwise medically significant. Treatment-emergent adverse events (TEAEs) are those that begin or worsen after the first dose through 30 days post-treatment, and include both serious and non-serious events. Treatment-related TEAEs are those reasonably related to the study intervention. Severity is graded per CTCAE v24.1: Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe/medically significant), Grade 4 (life-threatening/disabling), Grade 5 (death related to AE).

  Approximately 2 years 11 months

• Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Laboratory Values

  Number of participants with clinically meaningful change from baseline in laboratory parameters were reported. Clinically meaningful abnormalities (identified as laboratory values having CTCAE grades \>= 3). Laboratory investigation included hematology, biochemistry, urinalysis, and coagulation.

  Approximately 2 years 11 months

• Part 1A and 1B: Number of Participants With Clinically Meaningful Change From Baseline in Electrocardiogram (ECG)

  Number of participants with clinically significant change from baseline in ECG parameters were reported. Clinical Significance was decided by the investigator. The 12-lead ECGs were recorded after the participants have rested for at least 5 minutes in supine position. The parameters included heart rate (HR), Respiratory Rate, Pulse Rate, QRS, QT and QTcB calculated by the Bazett formula.

  Approximately 2 years 11 months

• Part 1A and 1B: Number of Participants With Clinically Relevant Changes From Baseline in Vital Signs

  Vital signs included oral body temperature, systolic blood pressure, diastolic blood pressure, and pulse rate. Clinical Relevance was decided by the investigator. Number of participants with clinically relevant change from baseline in vital signs were reported. Clinical relevance was defined as increase more than equal to (\>=) 3° temperature, \>40 beats heart rate increase, \>40 mmHG increase in systolic or diastolic blood pressure, \>10 breaths in respiratory rate increase.

  Approximately 2 years 11 months

• Part 1A and 1B: Number of Participants With Worsened Post Baseline Shift in Eastern Cooperative Oncology Group Performance Status

  The number of participants who experienced worse post baseline shift were assessed as per ECOG performance status score recorded during the treatment. The ECOG score is categorized as Grade 0, 1, 2, 3 and 4 where Grade 0=fully active, Grade 1=restricted in physically strenuous activity, Grade 2=unable to carry out any work activities, Grade 3=capable of only limited self-care and Grade 4=completely disabled.

  Approximately 2 years 11 months

Secondary Outcomes (17)

• 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

  Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)

• Part 1A and Part 1B: Area Under the Serum Concentration-Time Curve From Time Zero to Infinity (AUC 0-inf) of M6223

  Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)

• Part 1A and Part 1B: Area Under Serum Concentration-Time Curve Over a Dosing Interval From Time Zero to Tau (AUC-tau) of M6223

  Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycle 1 (Cycle is of 21 days in Q3W regimen)

• Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223

  Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)

• Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223

  Pre-dose up to 14 days (in Q2W regimen) or 21 days (in Q3W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen and each Cycle is of 21 days in Q3W regimen)

Study Arms (2)

Part 1A: M6223 Monotherapy

EXPERIMENTAL

Drug: M6223

Part1B: M6223 + Bintrafusp alfa

EXPERIMENTAL

Drug: Bintrafusp alfa; Drug: M6223

Interventions

M6223 DRUG

Participants received an intravenous (IV) infusion of M6223 at escalated doses every 2 weeks (Q2W) or every 3 weeks (Q3W) on Day 1 of each Cycle (Each cycle is of 14 days) according to the recommendation of the SMC(Safety Monitoring Committee) until the maximum tolerated dose(MTD) has been reached or confirmed disease progression.

Part 1A: M6223 Monotherapy

Bintrafusp alfa DRUG

Participants received an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression.

Part1B: M6223 + Bintrafusp alfa

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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 (\<=) 2, or other non-immune-related Grade \<= 2 not constituting a safety risk
• Participants with prior organ transplantation including allogeneic stem cell transplantation
• Participants with current significant cardiac conduction abnormalities, including corrected QT interval (QTcF, corrected with Fridericia formula) prolongation of \> 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 \[\<\] 6 months prior to enrollment), myocardial infarction (\< 6 months prior to enrollment), unstable angina, congestive heart failure (New York Heart Association Classification Class \>= II), deep vein thrombosis (\< 3 months prior to enrollment) or pulmonary thrombosis/embolism (\< 3 months prior to enrollment)

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (4)

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Next Oncology

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre

Toronto, Canada

Location

Related Publications (1)

• Naing A, McKean M, Tolcher A, Victor A, Hu P, Gao W, Nogueira Filho MAF, Kitzing T, Gleicher S, Holland D, Richter E, Tadjalli-Mehr K, Siu LL. TIGIT inhibitor M6223 as monotherapy or in combination with bintrafusp alfa in patients with advanced solid tumors: a first-in-human, phase 1, dose-escalation trial. J Immunother Cancer. 2025 Feb 10;13(2):e010584. doi: 10.1136/jitc-2024-010584.

  PMID: 39929671 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources
• INTR@PID Clinical Trial Program

MeSH Terms

Interventions

bintrafusp alfa protein, human

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

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

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 30, 2020
• First Posted: July 7, 2020
• Study Start: July 10, 2020
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: May 4, 2026
• Results First Posted: May 4, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (3); CA (1)