Clinical Trials /

First in Human Study of M6223 in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors

NCT04457778

Description:

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) and of M6223 combined with bintrafusp alfa (Part 1B) in participants with metastatic or locally advanced solid unresectable tumors.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: First in Human Study of M6223 in Participants With Metastatic or Locally Advanced Solid Unresectable Tumors
  • Official Title: 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

Clinical Trial IDs

  • ORG STUDY ID: MS201430_0001
  • NCT ID: NCT04457778

Conditions

  • Metastatic Solid Tumors

Interventions

DrugSynonymsArms
M6223Part 1A: M6223 Monotherapy
Bintrafusp alfaPart1B: M6223 + Bintrafusp alfa

Purpose

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) and of M6223 combined with bintrafusp alfa (Part 1B) in participants with metastatic or locally advanced solid unresectable tumors.

Trial Arms

NameTypeDescriptionInterventions
Part 1A: M6223 MonotherapyExperimental
  • M6223
Part1B: M6223 + Bintrafusp alfaExperimental
  • M6223
  • Bintrafusp alfa

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 (<=) 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) 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1A and 1B: Occurrence of Dose Limiting Toxicities (DLTs) During the DLT Observation Period (28 Days)
Time Frame:Day 1 to Day 28
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure: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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure: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 post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1A and Part 1B: Maximum Observed Serum Concentration (Cmax) of M6223
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1A and Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of M6223
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1A and Part 1B: Time to Reach Maximum Serum Concentration (Tmax) of M6223
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1A and Part 1B: Apparent Terminal Half-Life (t1/2) of M6223
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1A and Part 1B: Elimination Rate Constant (Lambda z) of M6223
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1, 2, and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1B: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1 and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part 1B: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa
Time Frame:Pre-dose up to 14 days post-dose of Cycles 1 and 4 (Each cycle is of 14 days)
Safety Issue:
Description:
Measure:Part IA and 1B: Immunogenicity of M6223 Measured by Antidrug Antibody (ADA) Assays
Time Frame:Pre-dose of Day 1 Cycle 1 (Cycle is 14 days) up to end of safety follow-up visit (up to a maximum of 2 years)
Safety Issue:
Description:
Measure:Part 1B: Immunogenicity of Bintrafusp alfa Measured by Antidrug Antibody (ADA) Assays
Time Frame:Pre-dose of Day 1 Cycle 1 (Cycle is 14 days) up to end of safety follow-up visit (up to a maximum of 2 years)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure:Part 1A and 1B: Overall Survival
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)
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • M6223
  • Bintrafusp alfa
  • Metastatic Solid Tumors

Last Updated

July 21, 2020