We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

M1231 in Participants With Solid Tumors

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04695847
Recruitment Status : Active, not recruiting
First Posted : January 5, 2021
Last Update Posted : December 7, 2022
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Metastatic Solid Tumors Esophageal Cancer Non-Small Cell Lung Cancer Drug: M1231 Phase 1

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 84 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : January 13, 2021
Estimated Primary Completion Date : July 15, 2023
Estimated Study Completion Date : March 27, 2024

Resource links provided by the National Library of Medicine


Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: Part 1: M1231
Participants 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.
 Drug: M1231
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 Name: Bispecific antibody drug conjugate (ADC)
Experimental: Part 2: Cohort A M1231: Metastatic NSCLC
Participants 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.
 Drug: M1231
M1231 will be administered at the dose determined as RDE in part 1, every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
Other Name: Bispecific antibody drug conjugate (ADC)
Experimental: Part 2: Cohort B M1231: Metastatic Esophageal Squamous Cell Carcinoma
Participants with metastatic esophageal squamous cell carcinoma will receive M1231 at the dose determined as recommended dose for expansion (RDE) in Part 1.
 Drug: M1231
M1231 will be administered at the dose determined as RDE in part 1, every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or any criterion for withdrawal from the study.
Other Name: Bispecific antibody drug conjugate (ADC)


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 Outcome Measures :
  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) ]

Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04695847


Locations
Layout table for location information
United States, Texas
MD Anderson Cancer Center - Clinical Cancer Prevention
Houston, Texas, United States, 77030
NEXT Oncology
San Antonio, Texas, United States, 78229
Canada, Ontario
Princess Margaret Cancer Centre
Toronto, Ontario, Canada, M5G 2M9
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
Layout table for investigator information
Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Additional Information:

Layout table for additonal information
Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT04695847    
Other Study ID Numbers: MS201668_0001
First Posted: January 5, 2021    Key Record Dates
Last Update Posted: December 7, 2022
Last Verified: December 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and the European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://bit.ly/IPD21

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
M1231
Non-Small Cell Lung Cancer
Metastatic Solid Tumors
 Esophageal cancer
Maximum tolerated dose
Pharmacokinetics
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Esophageal Neoplasms
Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gastrointestinal Neoplasms
 Digestive System Neoplasms
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Antibodies
Immunoglobulins
Immunoconjugates
Antibodies, Bispecific
Immunologic Factors
Physiological Effects of Drugs