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Completed

NCT Number: NCT04695847

M1231 in Participants With Solid Tumors

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.

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Key information

Conditions

Metastatic Solid Tumors Bronchial Neoplasms Carcinoma, Bronchogenic Carcinoma, Non-Small-Cell Lung Digestive System Diseases Digestive System Neoplasms Esophageal Cancer Esophageal Diseases Esophageal Neoplasms Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Neoplasms Lung Diseases Lung Neoplasms Neoplasms Neoplasms by Site Non-small Cell Lung Cancer Respiratory Tract Diseases Respiratory Tract Neoplasms Thoracic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Princess Margaret Cancer Centre, Toronto, Canada

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

M1231

Drug

M1231 will be administered at escalated doses every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.

Other names: Bispecific antibody drug conjugate (ADC)

Primary outcomes

  1. Part 1: Number of Participants with Dose Limiting Toxicities (DLTs)

    Time frame: Day 1 Up to Day 21

  2. Part 1: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs

    Time frame: From Baseline until 4 months

  3. Part 2: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators

    Time frame: From Baseline until 6 months

  4. Part 2: Number of Participants with Treatment Emergent Adverse Events (TEAEs) and Treatment Related TEAEs

    Time frame: From Baseline until 6 months

  5. Part 2: 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 6 months

Secondary outcomes

  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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)

  17. Part 1: Number of Participants With Anti-Drug Antibodies (ADA) against M1231

    Time frame: From Baseline until 4 months

  18. Part 1: Levels of Titers of Anti-Drug Antibody (ADA) against M1231

    Time frame: From Baseline until 4 months

  19. Part 1: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay

    Time frame: From Baseline until 4 months

  20. 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

  21. Part 1: Renal Clearance of Unconjugated Hemiasterlin Analogue (a tubulin inhibitor in tumor cells)

    Time frame: From Baseline until 4 months

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. Part 2: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay

    Time frame: From Baseline until 6 months

  28. 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

  29. 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

  30. 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

  31. 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

  32. 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

  33. 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

  34. 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

  35. 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

  36. 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

  37. 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

  38. 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

  39. 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

  40. 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

  41. 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

  42. 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

  43. 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

  44. Part 2:Number of Participants with Anti-Drug Antibodies (ADA) against M1231

    Time frame: From Baseline until 6 months

  45. Part 2: Levels of Titers of Anti-Drug Antibody (ADA) against M1231

    Time frame: From Baseline until 6 months

  46. 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)

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study 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

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jan 5, 2021
Registry last updated
Jul 7, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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