First in Human Study of M6223

NCT ID: NCT04457778

Last Updated: 2023-12-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 58 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-07-10
• Study Completion Date: 2023-06-23

Brief Summary

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.

Conditions

Metastatic Solid Tumors

Keywords

M6223; Bintrafusp alfa; Metastatic Solid Tumors

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part 1A: M6223 Monotherapy

Group Type: EXPERIMENTAL

M6223

Intervention Type: DRUG

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.

Part1B: M6223 + Bintrafusp alfa

Group Type: EXPERIMENTAL

Bintrafusp alfa

Intervention Type: DRUG

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

M6223

Intervention Type: DRUG

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.

Interventions

M6223

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.

Intervention Type: DRUG

Bintrafusp alfa

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

Intervention Type: DRUG

M6223

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.

Intervention Type: DRUG

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

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

Sarah Cannon Research Institute

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Next Oncology

San Antonio, Texas, United States

Princess Margaret Cancer Centre

Toronto, , Canada

Countries

Germany; United States; Canada

References

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.

Reference Type: DERIVED

PMID: 39929671 (View on PubMed)

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201430_0001

Trial Awareness and Transparency website

https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

https://www.intrapidclinicaltrials.com/en

INTR@PID Clinical Trial Program

Other Identifiers

MS201430_0001

Identifier Type: -

Identifier Source: org_study_id