Clinical Trials /

M1231 in Participants With Solid Tumors

NCT04695847

Description:

This study is to establish a safe and tolerable dose and to investigate pharmacokinetics and the first clinical efficacy signals of M1231 as a single agent in participants with solid tumors (Part 1) and with metastatic Non-small Cell Lung Cancer (NSCLC) and esophageal squamous cell carcinoma (Part 2). Dose escalation will be followed by the dose expansion once the maximum tolerated dose (MTD) or recommended dose for Expansion (RDE) has been defined.

Related Conditions:
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: M1231 in Participants With Solid Tumors
  • Official Title: A Phase I Open Label First in Human Dose Escalation and Expansion Study of the Bispecific Anti-Mucin 1 - Epidermal Growth Factor Receptor Antibody Drug Conjugate M1231 as a Single Agent in Participants With Advanced Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: MS201668_0001
  • NCT ID: NCT04695847

Conditions

  • Metastatic Solid Tumors
  • Esophageal Cancer
  • Non-Small Cell Lung Cancer

Interventions

DrugSynonymsArms
M1231Bispecific antibody drug conjugate (ADC)Part 1: M1231
M1231Bispecific antibody drug conjugate (ADC)Part 2: Cohort A M1231: Metastatic NSCLC

Purpose

This study is to establish a safe and tolerable dose and to investigate pharmacokinetics and the first clinical efficacy signals of M1231 as a single agent in participants with solid tumors (Part 1) and with metastatic Non-small Cell Lung Cancer (NSCLC) and esophageal squamous cell carcinoma (Part 2). Dose escalation will be followed by the dose expansion once the maximum tolerated dose (MTD) or recommended dose for Expansion (RDE) has been defined.

Trial Arms

NameTypeDescriptionInterventions
Part 1: M1231ExperimentalParticipants with solid tumors for whom no effective standard therapy exists will be included in this Part. Dose escalation of M1231 will be administered as single agent.
  • M1231
Part 2: Cohort A M1231: Metastatic NSCLCExperimentalParticipants with metastatic Non-small Cell Lung Cancer (NSCLC) expressing Epidermal Growth Factor Receptor (EGFR) and Mucin 1 (MUC1) on archival tumor tissue will receive M1231 at the dose determined as recommended dose for expansion (RDE) in Part 1.
  • M1231
Part 2: Cohort B M1231: Metastatic Esophageal Squamous Cell CarcinomaExperimentalParticipants with metastatic esophageal squamous cell carcinoma will receive M1231 at the dose determined as recommended dose for expansion (RDE) in Part 1.
  • M1231

Eligibility Criteria

        Inclusion Criteria:

        For Part 1 and 2:

          -  The Investigator reviews the medical history, menstrual history, and recent sexual
             activity to decrease the risk for inclusion of a female with an early undetected
             pregnancy

        For Part 1:

          -  Locally advanced or metastatic disease that is intolerant or refractory to standard
             therapy or for which no standard therapy is judged appropriate by the investigator

          -  Participants with solid tumors expressing or likely to expressing EGFR and MUC1,
             including but not limited to lung cancer, squamous esophageal cancer, head and neck
             squamous cell carcinoma, breast cancer and ovarian cancer, should be prioritized for
             enrollment

        For Part 2:

          -  Cohort A: Participants must have progressed on at least 2 prior lines of therapy

          -  Cohort B: Participants must have progressed on at least 1 prior line of platinum
             therapy and for microsatellite instability-high (MSI-H) at least 1 prior line with
             pembrolizumab

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status less than 1

          -  Tumor accessible for biopsies and agreement to conduct fresh tumor biopsies at
             Screening and before first dosing

        Exclusion Criteria:

          -  Participants not recovered from adverse events (AE) (less than or equal to Grade 1)
             related to previous therapies (excluding Grade 1 neuropathy and alopecia)

          -  Participant has a history of a second malignancy within 3 years before the date of
             enrollment

          -  Known brain metastasis

          -  Unstable angina, myocardial infarction, congestive heart failure or a coronary
             revascularization procedure within 180 days of study entry

          -  Cerebrovascular accident/stroke

          -  Diagnosis of fever within 1 week prior to study intervention administration

          -  Life expectancy of less than 4 months

          -  Steroid therapy for anti-neoplastic intent taken less than 7 days prior to the first
             dose of study intervention

          -  Major surgery within 4 weeks prior to start of study intervention

          -  Received growth factors (including erythropoietin (EPO), darbepoetin,
             granulocyte-colony stimulating factor (G-CSF), granulocyte macrophage-colony
             stimulating factor (GM-CSF), and platelet stimulators or transfusions within 2 weeks
             prior to the first day of study intervention
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)
Time Frame:Day 1 Up to Day 21
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part 1:Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1231 (Conjugated Payload), Total Antibody and Free Payload M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Area Under the Concentration-time Curve From Time Zero to the Last Sampling time (AUC 0-tlast) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Dose Normalized Area Under Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Area Under Concentration From Time tlast Extrapolated to Infinity (AUCextra%) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Observed Concentration At The End of The Infusion Period (Ceoi) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Total Body Clearance (CL) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Plasma Concentration Observed Immediately Before Next Dosing (Ctrough) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Accumulation Ratio for AUCtau (Racc[AUCtau]) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Accumulation Ratio for Maximum Observed Concentration (Racc[Cmax]) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Apparent Terminal Half-life (t1/2) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Time to Reach Maximum Plasma Concentration (tmax) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 15 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 4 months
Safety Issue:
Description:
Measure:Part 1: Number of Participants with Corrected QT Interval (QTc)
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 8 (each Cycle is of 21 days)
Safety Issue:
Description:
Measure:Part 1: Number of Participants With Anti-Drug Antibodies (ADA) against M1231
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Levels of Titers of Anti-Drug Antibody (ADA) against M1231
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Level of Epidermal Growth Factor Receptor (EGFR) Protein Expression in Archival Tumor Tissue Determined by Assay
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Renal Clearance of Unconjugated Hemiasterlin Analogue (a tubulin inhibitor in tumor cells)
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1:Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 1: Progression-free survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators
Time Frame:From Baseline until 4 months
Safety Issue:
Description:
Measure:Part 2: Progression-free survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Overall Survival (OS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Level of Epidermal Growth Factor Receptor (EGFR) Protein Expression in Archival Tumor Tissue Determined by Assay
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1231 (Conjugated Payload), Total Antibody and Free Payload M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2: Dose Normalized Area Under Concentration-Time Curve Within One Dosing Interval (AUC0-tau/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Area Under the Concentration-time Curve From Time Zero to the Last Sampling time (AUC 0-tlast) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2: Dose Normalized Area Under Concentration-Time Curve From Time Zero to the Last Sampling Time (AUC0-last/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Area Under the Plasma Concentration-Time Curve From Time Zero to Infinity (AUC0-inf) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Dose Normalized Area Under Concentration-Time Curve From Time Zero (dosing time) Extrapolated to Infinity (AUC0-inf/Dose) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Area Under Concentration From Time tlast Extrapolated to Infinity (AUCextra%) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Observed Concentration At The End of The Infusion Period (Ceoi) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2: Total Body Clearance (CL) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Plasma Concentration Observed Immediately Before Next Dosing (Ctrough) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Accumulation Ratio for AUCtau (Racc[AUCtau]) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Accumulation Ratio for Maximum Observed Concentration (Racc[Cmax]) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Apparent Terminal Half-life (t1/2) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Time to Reach Maximum Plasma Concentration (tmax) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Apparent Volume of Distribution During Terminal Phase Following Extravascular Administration (Vz) of M1231 (Conjugated Payload), Total Antibody and Free Payload for M1231
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 3 and every second cycle from Cycle 4 (each cycle is of 21 days), assessed up to approximately 6 months
Safety Issue:
Description:
Measure:Part 2:Number of Participants with Anti-Drug Antibodies (ADA) against M1231
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Levels of Titers of Anti-Drug Antibody (ADA) against M1231
Time Frame:From Baseline until 6 months
Safety Issue:
Description:
Measure:Part 2: Number of Participants with Corrected QT Interval (QTc)
Time Frame:Cycle 1 Day 1 to Cycle 3 Day 8 (each Cycle is of 21 days)
Safety Issue:
Description:

Details

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

Trial Keywords

  • M1231
  • Non-Small Cell Lung Cancer
  • Metastatic Solid Tumors
  • Esophageal cancer
  • Maximum tolerated dose
  • Pharmacokinetics

Last Updated

March 22, 2021