- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04457778
First in Human Study of M6223
December 7, 2023 updated by: EMD Serono Research & Development Institute, Inc.
Phase I, First-in-Human, Open-Label, Multiple Ascending Dose Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Activity of M6223, an Inhibitor of TIGIT, as Single Agent and in Combination With Bintrafusp Alfa (Anti-PDL1/ TGFß Trap) in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors
The main purpose of this study is 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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Study Type
Interventional
Enrollment (Actual)
58
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Contact
- Name: Communication Center
- Phone Number: 49 6151 72 5200
- Email: service@emdgroup.com
Study Locations
-
-
-
Toronto, Canada
- Princess Margaret Cancer Centre
-
-
-
-
Tennessee
-
Nashville, Tennessee, United States, 37203
- Sarah Cannon Research Institute
-
-
Texas
-
Houston, Texas, United States, 77030
- MD Anderson Cancer Center
-
San Antonio, Texas, United States, 78229
- NEXT Oncology
-
-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Description
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 (<=) 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 prior toxicity related to an immune checkpoint inhibitor Grade greater than equal to (>=) 3 NCI-CTCAE Version 5.0 unless resolved to Grade <= 1 prior to study inclusion
- 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)
- Other protocol defined exclusion criteria may apply
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Sequential Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Part 1A: M6223 Monotherapy
|
Participants will receive 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.
Participants will receive an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.
|
Experimental: Part1B: M6223 + Bintrafusp alfa
|
Participants will receive 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.
Participants will receive an IV infusion of M6223 at escalated doses Q2W on Day 1 of each Cycle (Each cycle is of 21 days) according to the recommendation of the SMC until the MTD has been reached or confirmed disease progression.
Participants will receive an IV infusion of bintrafusp alfa Q2W on Day 1 of each Cycle (Cycle is 14 days) until confirmed disease progression.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days)
Time Frame: Day 1 to Day 28
|
Day 1 to Day 28
|
Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events (TRAEs) According to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE) version 5
Time Frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Part IA and IB: Occurrence of Treatment-Emergent Adverse Events (TEAEs) as per Severity and Deaths
Time Frame: Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from first study drug administration to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Clinical Laboratory Measures
Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Electrocardiogram Findings
Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Part IA and IB: Occurrence of Clinically Significant Change From Baseline in Vital Signs
Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Part IA and IB: Occurrence of Change From Baseline in Eastern Cooperative Oncology Group Performance Status
Time Frame: Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Time from baseline to final assessment at end of safety follow-up visit (up to a maximum of approximately 2 years)
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
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
Time Frame: 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)
|
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
Time Frame: 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)
|
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 (τ) (AUCτ) of M6223
Time Frame: 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)
|
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: Maximum Observed Serum Concentration (Cmax) of M6223
Time Frame: 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)
|
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
Time Frame: 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)
|
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: Time to Reach Maximum Serum Concentration (Tmax) of M6223
Time Frame: 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)
|
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: Apparent Terminal Half-Life (t1/2) of M6223
Time Frame: 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)
|
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: Elimination Rate Constant (Lambda z) of M6223
Time Frame: 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)
|
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 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa
Time Frame: Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
|
Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
|
Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa
Time Frame: Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
|
Pre-dose up to 14 days (in Q2W regimen) post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days in Q2W regimen)
|
Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays
Time Frame: Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
|
Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
|
Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays
Time Frame: Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
|
Pre-dose of Day 1 Cycle 1 (Each Cycle is of 14 days in Q2W regimen) up to end of safety follow-up visit (up to a maximum of 2 years)
|
Part 1A and 1B: Change from Baseline in QT Interval
Time Frame: From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen)
|
From Day 1 Cycle 1 (Baseline) up to Day 1 Cycle 7 (Each Cycle is of 14 days in Q2W regimen and 21 days in Q3W regimen)
|
Part 1A and IB: Best Overall Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
Time Frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
Part 1A and 1B: Duration of Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
Time Frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
Part 1A and 1B: Time to Tumor Response According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
Time Frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
Part 1A and 1B: Disease Control According to Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1) Assessed as per Investigator
Time Frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
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
Time Frame: From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
From first study drug administration until documented disease progression or death due to any cause whichever occurs first, (approximately assessed up to 2 years)
|
Part 1A and 1B: Overall Survival
Time Frame: Time from first treatment to end of study (planned 12 months after last patient started treatment)
|
Time from first treatment to end of study (planned 12 months after last patient started treatment)
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Collaborators
Investigators
- Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 10, 2020
Primary Completion (Actual)
June 23, 2023
Study Completion (Actual)
June 23, 2023
Study Registration Dates
First Submitted
June 30, 2020
First Submitted That Met QC Criteria
June 30, 2020
First Posted (Actual)
July 7, 2020
Study Record Updates
Last Update Posted (Actual)
December 8, 2023
Last Update Submitted That Met QC Criteria
December 7, 2023
Last Verified
November 1, 2023
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- MS201430_0001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
NO
IPD Plan Description
We are committed to enhancing public health through responsible sharing of clinical trial data.
Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research.
Further information on how to request data can be found on our website bit.ly/IPD21
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Solid Tumors
-
Incyte CorporationRecruitingA Study to Evaluate the Safety of INCA33890 in Participants With Advanced or Metastatic Solid TumorsAdvanced Solid Tumors | Solid Tumors | Metastatic Solid TumorsUnited States, Spain, United Kingdom, France, Italy, Denmark, Switzerland
-
Incyte Biosciences Japan GKCompletedAdvanced Solid Tumors | Metastatic Solid TumorsJapan
-
Memorial Sloan Kettering Cancer CenterKyowa Hakko Kirin Pharma, Inc.CompletedAdvanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Bristol-Myers SquibbCompletedAdvanced Solid Tumors | Metastatic Solid TumorsKorea, Republic of, Canada, Australia
-
Alphamab (Australia) Co Pty Ltd.RecruitingAdvanced Solid Tumors | Metastatic Solid TumorsAustralia
-
Jiangsu Simcere Pharmaceutical Co., Ltd.UnknownAdvanced Solid Tumors | Metastatic Solid TumorsChina
-
NeuPharma, Inc.RecruitingLocally Advanced Solid Tumors | Metastatic Solid TumorsUnited States
-
Genentech, Inc.RecruitingAdvanced Solid Tumors | Metastatic Solid TumorsCanada, Korea, Republic of, United States, Brazil, Australia, Argentina, Spain, New Zealand, Poland
-
OBI Pharma, IncTerminatedLocally Advanced Solid Tumors | Metastatic Solid TumorsUnited States, Taiwan
-
University of AlbertaWithdrawnLocally Advanced Solid Tumors | Metastatic Solid TumorsCanada
Clinical Trials on M6223
-
EMD Serono Research & Development Institute, Inc.Merck KGaA, Darmstadt, Germany; Gilead Sciences; Nektar TherapeuticsRecruitingLocally Advanced or Metastatic Urothelial CarcinomaKorea, Republic of, United States, Taiwan, Australia, United Kingdom, France, Greece, Italy, Belgium, Spain, Canada, Denmark, Germany