Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01)

Colorectal Cancer Clinical Trial

Official title:

A Phase I, Multicenter, Open-Label First in Human Study of Anti-CEACAM5 Antibody Drug Conjugate M9140 in Participants With Advanced Solid Tumors (PROCEADE-CRC-01)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05464030
• Other study ID #: MS202329_0001
• Secondary ID: 2022-500508-23-0
• Status: Recruiting
• Phase: Phase 1
• Start date: August 4, 2022
• Est. completion date: February 27, 2026

Study information

• Verified date: June 2024
• Source: EMD Serono
• Contact: US Medical Information
• Phone: 888-275-7376
• Email: eMediUSA[@]emdserono.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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. This study contains 2 parts: Dose escalation (Part 1) and dose expansion (Part 2).

Study details include:

• Study Duration per participant: Approximately 4 months for Part 1 and 8 months for Part 2

• M9140 is not available through an expanded access program

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: February 27, 2026
• Est. primary completion date: February 27, 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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) below or equal to 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

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Drug:
• M9140
M9140 will be administered at an escalated dose until Maximum tolerated dose (MTD) and/or a safe recommended Dose for Expansion (RDE) is determined in Part 1 of the study.
• M9140
M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative regimen and combination regimen.
• Bevacizumab
Bevacizumab will be administered intravenously as per standard of care.
• Capecitabine
Capecitabine will be administered orally as per standard of care.

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital - Dept of Gastroenterology	Chuo-ku
Spain	Hospital Clinic de Barcelona	Barcelona
Spain	Hospital Universitari Vall d'Hebron - VHIR	Barcelona
Spain	Hospital Universitario Quironsalud Madrid - NEXT Oncology	Madrid
United States	MD Anderson Cancer Center - Oncology	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,  Japan,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)		up to 4 months
Primary	Part 1: Recommended Dose Expansion (RDE) of M9140		up to 4 months
Primary	Parts 2B and 2C: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)		up to 8 months
Primary	Part 2A: Number of Participants with Adverse Events (AEs)		up to 8 months
Primary	Part 2A: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators		Time from first study treatment throughout the study duration until progressive disease or death up to approximately 8 months
Primary	Part 2A: 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 study treatment to planned assessment at approximately 8 months
Secondary	Parts 1 and 2: Pharmacokinetic (PK) Plasma Concentrations of M9140		Part 1: Pre-dose up to 4 months; Part 2: Pre-dose up to 8 months
Secondary	Parts 1 and 2: Number of Participants with Anti-Drug Antibodies (ADA) Against M9140		Part 1: up to 4 months; Part 2: up to 8 months
Secondary	Parts 1 and 2: Levels of Titers of Anti-Drug Antibody (ADA) Against M9140		Part 1: up to 4 months; Part 2: up to 8 months
Secondary	Parts 1 and 2A: Number of Participants with Clinically Significant Changes from Baseline in Triplicate 12-Lead Electrocardiogram (ECG)		Part 1: up to 4 months; Part 2: up to 8 months
Secondary	Parts 1 and 2A: Change from Baseline in QTc (?QTc) Interval		Part 1: baseline, up to 4 months; Part 2: baseline up to 8 months
Secondary	Parts 1, 2B and 2C: Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigators		Time from first study treatment throughout the study duration until progressive disease or death up to approximately 4 months and 8 months
Secondary	Parts 1, 2B and 2C: Duration of Response (DoR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator		Time from first study treatment to planned assessment at approximately 4 months and 8 months
Secondary	Parts 2A, 2B and 2C: Time to Response		Time from first study treatment to planned assessment at approximately 8 months
Secondary	Parts 1, 2A, 2B and 2C: 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 study treatment to planned assessment at approximately 4 months and 8 months
Secondary	Part 2A: Overall Survival		Time from first study treatment to planned assessment at approximately 8 months
Secondary	Part 2A: Number of Participants with Symptomatic Adverse Events (AEs)		up to 8 months

External Links

•   Trial Awareness and Transparency website