M1231 in Participants With Solid Tumors

NCT04695847 | Completed Phase 1 FDA Drug

• 1 other identifier: MS201668_0001
• Study Type: interventional
• Target: 23
• Locations: 2 countries
• Sites: 3

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.

Conditions

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

Keywords

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

Outcome Measures

Primary Outcomes (5)

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

  Day 1 Up to Day 21

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

  From Baseline until 4 months

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

  From Baseline until 6 months

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

  From Baseline until 6 months

• Part 2: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Investigators

  From Baseline until 6 months

Secondary Outcomes (46)

• Part 1:Area Under Plasma Concentration-Time Curve Within One Dosing Interval (AUC0-tau) of M1231 (Conjugated Payload), Total Antibody and Free Payload M1231

  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

• 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

  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

• 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

  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

• 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

  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

• 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

  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

Study Arms (3)

Part 1: M1231

EXPERIMENTAL

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

Part 2: Cohort A M1231: Metastatic NSCLC

EXPERIMENTAL

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

Part 2: Cohort B M1231: Metastatic Esophageal Squamous Cell Carcinoma

EXPERIMENTAL

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

Interventions

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.

Also known as: Bispecific antibody drug conjugate (ADC)

Part 1: M1231

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For Part 1 and 2:
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (3)

MD Anderson Cancer Center - Clinical Cancer Prevention

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

Princess Margaret Cancer Centre

Toronto, Canada

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Esophageal Neoplasms; Carcinoma, Non-Small-Cell Lung

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2021
• First Posted: January 5, 2021
• Study Start: January 13, 2021
• Primary Completion: June 23, 2023
• Study Completion: June 23, 2023
• Last Updated: July 7, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1); US (2)