Clinical Trials /

M1774 in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors

NCT04170153

Description:

This is an open-label, Phase I, first-in-human (FIH) multicenter, clinical study conducted in multiple parts to establish the safety, tolerability and Pharmacokinetic/Pharmacodynamic (PK/PD) profile (with and without food) of M1774.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: M1774 in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors
  • Official Title: An Open-label, Multicenter Trial of the Safety, Tolerability, and Pharmacokinetic/Pharmacodynamic Profile of M1774 in Participants With Metastatic or Locally Advanced Unresectable Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MS201924_0001
  • SECONDARY ID: 2019-002203-18
  • NCT ID: NCT04170153

Conditions

  • Metastatic or Locally Advanced Unresectable Solid Tumors

Interventions

DrugSynonymsArms
M1774Part A1: Monotherapy Dose Escalation

Purpose

This is an open-label, Phase I, first-in-human (FIH) multicenter, clinical study conducted in multiple parts to establish the safety, tolerability and Pharmacokinetic/Pharmacodynamic (PK/PD) profile (with and without food) of M1774.

Trial Arms

NameTypeDescriptionInterventions
Part A1: Monotherapy Dose EscalationExperimentalParticipants will receive M1774 once daily under fasting condition.
  • M1774
Part A2 - Preliminary Food Effect AssessmentExperimentalParticipants in the food effect assessment will receive M1774 at the dose and schedule determined as recommended dose for expansion (RDE) in Part A1. A single dose of M1774 will be administered on Day -7 under a fed (high-fat meal) or fasted condition, followed by a 1-week washout period.
  • M1774
Part A3 - Monotherapy ExpansionExperimentalAfter completion of the scheduled food effect assessments, participants will follow the same schedule as participants in Part A1. Participants will be administered M1774 at a dose and schedule determined as RDE in Part A1.
  • M1774

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than or equal to
             (<=) 1

          -  Have clinically controlled brain metastases, which is defined as individuals with
             central nervous system metastases that have been treated for, are asymptomatic, and
             have discontinued steroids (for the treatment of brain metastases) for greater than
             (>) 28 days may be enrolled

          -  Participants with meningeal carcinomatosis are excluded

          -  In Part A3, measurable disease according to Response Evaluation Criteria in Solid
             Tumors (RECIST) Version 1.1

          -  Contraceptive use by males or females will be consistent with local regulations on
             contraception methods for those participating in clinical studies

          -  Female participants are not pregnant or breastfeeding

          -  Not a women of childbearing potential (WOCBP)

          -  Other protocol defined inclusion criteria could apply

        Exclusion Criteria:

          -  Continuance of toxicities due to prior anticancer therapies (example, radiotherapy,
             chemotherapy, immunotherapies, et cetera [etc]) that do not recover to <= Grade 1

          -  Unstable angina, myocardial infarction, congestive heart failure >= II) or a coronary
             revascularization procedure within 180 days of study entry. Calculated QTc average
             (using the Fridericia correction calculation) of > 450 msec for males and > 470 msec
             for females

          -  Active fungal, bacterial and/or viral infection. Individuals with known human
             immunodeficiency virus and/or viral hepatitis (B and/or C) are excluded. However,
             individual with hepatitis C treated with curative therapy are not considered actively
             infected

          -  Treatment with live or live attenuated vaccine within 30 days of dosing

          -  Any other clinical condition or uncontrolled concurrent illness which in the
             Investigator's opinion would not make the participant a good candidate for the
             clinical study

          -  Prohibited concomitant medication, as per Protocol

          -  Another investigational drug within 28 days or 5 half-lives, whichever is shorter,
             prior to start of administration of study intervention

          -  No prior Ataxia telangiectasia mutated and Rad3-related (ATR) inhibitor and/or CHK1
             inhibitor

          -  Participants who cannot comply with restrictions for medications or food

          -  Other protocol defined exclusion criteria could apply
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A1: Occurrence of Dose-Limiting Toxicities (DLTs) During the DLT Observation Period
Time Frame:Day 1 to Day 21 of Cycle 1 (Each Cycle is of 21 days)
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part A1 and A3: Maximum Observed Plasma Concentration (Cmax) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Time to Reach Maximum Plasma Concentration (tmax) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Area Under the Plasma Concentration Curve From Time Zero to 24 Hours Post Dose AUC(0-24h) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Apparent Terminal Half-life (t1/2) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Apparent Total Body Clearance From Plasma (CL/f) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Apparent Clearance Body Clearance at Steady State Following Extravascular Administration (CLss/F) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Accumulation Ratio for Area Under the Plasma Concentration Concentration-Time Curve (Racc[AUC]) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Accumulation Ratio of Maximum Observed Plasma Concentration (Racc[Cmax]) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post-dose of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Area Under Concentration From Time tlast Extrapolated to Infinity (AUCextra%) of M1774
Time Frame:Cycle 1 Day 1 and Day 8: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A1 and A3: Number of Participants With Corrected QT (QTc) Interval
Time Frame:Baseline up to Day 8
Safety Issue:
Description:
Measure:Part A2: Occurrence of Treatment-emergent Adverse Events (TEAEs), Treatment-related Adverse Events (AEs) and Death According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A2: Number of Participants With Grade 3 or Higher Laboratory Findings According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 5.0
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A2: Number of Participants With Abnormalities in Vital Signs
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A2: Number of Participants With Clinical Significant Abnormalities in Electrocardiogram (ECG) Findings
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A2: Time to Reach Maximum Plasma Concentration (tmax) Under Fed/Fasted Ratio of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Apparent Terminal Half-life (t1/2) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Apparent Total Body Clearance From Plasma (CL/f) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz/F) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Dose Normalized Area Under Concentration Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to 24 Hours (AUC0-24h/Dose) Post dose of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Dose Normalized Maximum Observed Plasma Concentration (Cmax/Dose) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Area Under Concentration From Time tlast Extrapolated to Infinity (AUCextra%) of M1774
Time Frame:Cycle 1 Day -7 and Day 1: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Cumulative Amount Excreted From Time Zero (dosing time) to Infinity (Ae0-inf) of M1774
Time Frame:Cycle 1 Day -7: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Cumulative Amount Excreted From Time Zero to Time After Dosing (Ae0-t) of M1774
Time Frame:Cycle 1 Day -7: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Cumulative Percentage of Dose Excreted From Time Zero to Time After Dosing (Ae0-t%) of M1774
Time Frame:Cycle 1 Day -7: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Renal Clearance (CLr) of M1774
Time Frame:Cycle 1 Day -7: Pre-dose up to 24 hours post-dose (Each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part A2: Number of Participants With Corrected QT (QTc) Interval
Time Frame:Baseline up to Day 8
Safety Issue:
Description:
Measure:Part A3: Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A3: Number of Participants With Clinical Benefit According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:Participants with a clinical benefit, defined as an objective response or stable disease for at least 6 months, as determined by the Investigator through the use of RECIST version 1.1.
Measure:Part A3: Progression-Free Survival (PFS) as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:
Measure:Part A3: Overall Survival (OS) According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1
Time Frame:Baseline up to 30 days after the last dose of study treatment, assessed up to approximately 2.2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • M1774
  • ATR inhibitor
  • Metastatic or Locally Advanced Unresectable Solid Tumors

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