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| Name | Class |
|---|---|
| Merck KGaA, Darmstadt, Germany | INDUSTRY |
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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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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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. |
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| 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
For Part 1 and 2:
For Part 1:
For Part 2:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Medical Responsible | Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| MD Anderson Cancer Center - Clinical Cancer Prevention | Houston | Texas | 77030 | United States | ||
| NEXT Oncology |
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| Label | URL |
|---|---|
| Trial Awareness and Transparency website | View source |
| US Medical Information website, Medical Resources | View source |
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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
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| ID | Term |
|---|---|
| D004938 | Esophageal Neoplasms |
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
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| M1231 | Drug | 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. |
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| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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) |
| Part 1: Number of Participants With Anti-Drug Antibodies (ADA) against M1231 | From Baseline until 4 months |
| Part 1: Levels of Titers of Anti-Drug Antibody (ADA) against M1231 | From Baseline until 4 months |
| Part 1: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay | From Baseline until 4 months |
| Part 1: Level of Epidermal Growth Factor Receptor (EGFR) Protein Expression in Archival Tumor Tissue Determined by Assay | From Baseline until 4 months |
| Part 1: Renal Clearance of Unconjugated Hemiasterlin Analogue (a tubulin inhibitor in tumor cells) | From Baseline until 4 months |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Part 2: Level of Mucin 1 (MUC1) Protein Expression in Archival Tumor Tissue Determined by Assay | From Baseline until 6 months |
| Part 2: Level of Epidermal Growth Factor Receptor (EGFR) Protein Expression in Archival Tumor Tissue Determined by Assay | From Baseline until 6 months |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| 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 |
| Part 2:Number of Participants with Anti-Drug Antibodies (ADA) against M1231 | From Baseline until 6 months |
| Part 2: Levels of Titers of Anti-Drug Antibody (ADA) against M1231 | From Baseline until 6 months |
| 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) |
| San Antonio |
| Texas |
| 78229 |
| United States |
| Princess Margaret Cancer Centre | Toronto | Canada |
| D006258 |
| Head and Neck Neoplasms |
| D004066 | Digestive System Diseases |
| D004935 | Esophageal Diseases |
| D005767 | Gastrointestinal Diseases |
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
| D013899 | Thoracic Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |