Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in advanced solid tumors. Study details include: Study Duration per participant: Approximately 4 months M9140 is not available through an expanded access program

Official Title
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A Phase I, Multicenter, Open-Label First in Human Study of Anti-CEACAM5 Antibody Drug Conjugate M9140 in Participants With Advanced Solid Tumors

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: M9140


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants with documented histopathological diagnosis of locally advanced or metastatic colorectal cancer (CRC), who were intolerant/refractory to or progressed after standard systemic therapies for the advanced/metastatic stage, if locally indicated and available to the participant. Participants with a known microsatellite instability high (MSI-H) status must have received treatment with an immune checkpoint inhibitor (if locally indicated and available) unless contraindicated. Eastern Cooperative Oncology Group Performance Status (ECOG PS) less than (<) 1 Participants with adequate hematologic, hepatic and renal function as defined in protocol Other protocol defined inclusion criteria could apply Exclusion Criteria: Participant has a history of malignancy within 3 years before the date of enrollment (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, benign prostate neoplasm/hypertropia, or malignancy that in the opinion of the Investigator, with concurrence with the Sponsor's Medical Monitor, is considered cured with minimal risk of recurrence within 3 years) Participants with known brain metastases, except those meeting the following criteria: Brain metastases that have been treated locally and are clinically stable for at least 4 weeks prior to the start of treatment; No ongoing neurological symptoms that are related to the brain localization of the disease (sequelae that are a consequence of the treatment of the brain metastases are acceptable) Participants with diarrhea (liquid stool) or ileus Grade > 1 Participants with active chronic inflammatory bowel disease (e.g., ulcerative colitis, Crohn's disease, intestinal perforation) and/or bowel obstruction Unstable angina, myocardial infarction, congestive heart failure (New York Heart Association [NYHA] >= II) or a coronary revascularization procedure within 180 days of study entry. Calculated QTc average (using the Fridericia correction calculation) of > 470 milliseconds (ms) Cerebrovascular accident/stroke (< 6 months prior to enrollment) Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: M9140<br> | Drug: M9140<br>* M9140 will be administered at an escalated dose until Maximum tolerated dose (MTD) and/or a safe recommended Dose for Expansion (RDE) is determined.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs) |  | up to 4 months | 
| Recommended Dose Expansion (RDE) of M9140 |  | up to 4 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic (PK) Plasma Concentrations of M9140 |  | Pre-dose up to 4 months | 
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators |  | Time from first dose of study treatment up to planned assessment at 4 months or until progressive disease or death | 
| Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators |  | Time from first dose of study treatment up to planned assessment at 4 months or until progressive disease or death | 
| Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators |  | Time from first dose of study treatment up to planned assessment at 4 months or until progressive disease or death | 
| Number of Participants with Anti-Drug Antibodies (ADA) Against M9140 |  | up to 4 months | 
| Levels of Titers of Anti-Drug Antibody (ADA) Against M9140 |  | up to 4 months | 
| Number of Participants with Clinically Significant Changes from Baseline in Triplicate 12-Lead Electrocardiogram (ECG) |  | up to 3 months | 
| Change from Baseline in QTc (ΔQTc) Interval |  | baseline, up to 3 months |