M1231 in Participants With Solid Tumors

Non-Small Cell Lung Cancer Clinical Trial

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 Details — Status: Completed

Administrative data

• NCT number: NCT04695847
• Other study ID #: MS201668_0001
• Status: Completed
• Phase: Phase 1
• Start date: January 13, 2021
• Est. completion date: June 23, 2023

Study information

• Verified date: July 2023
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 23
• Est. completion date: June 23, 2023
• Est. primary completion date: June 23, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Esophageal Cancer
• Esophageal Neoplasms
• Metastatic Solid Tumors
• Non-Small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Princess Margaret Cancer Centre	Toronto
United States	MD Anderson Cancer Center - Clinical Cancer Prevention	Houston	Texas
United States	NEXT Oncology	San Antonio	Texas

Sponsors (2)

Lead Sponsor	Collaborator
EMD Serono Research & Development Institute, Inc.	Merck KGaA, Darmstadt, Germany

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

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

External Links

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