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

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)

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

Study Overview

• Status: Active, not recruiting
• Conditions: Colorectal Cancer
• Intervention / Treatment: Drug: M9140; Drug: Bevacizumab; Drug: Capecitabine; Drug: M9140; Drug: 5-fluorouracil (5-FU); Drug: Folinic acid

• Study Type: Interventional
• Enrollment (Actual): 220
• Phase: Phase 1

Contacts and Locations

Study Locations

• Canada
  • Ottawa, Canada
    • The Ottawa Hospital Cancer Centre
  • Toronto, Canada
    • University Health Network - Princess Margaret Cancer Centre
• Japan
  • Chūōku, Japan
    • National Cancer Center Hospital - Dept of Gastroenterology
  • Kashiwa-shi, Japan
    • National Cancer Center Hospital East
  • Kitaadachi-gun, Japan
    • Saitama Cancer Center
  • Kōtoku, Japan
    • Cancer Institute Hospital of JFCR
  • Nagoya, Japan
    • Aichi Cancer Center Hospital
  • Osakasayama-shi, Japan
    • Kindai University Hospital
  • Sunto-gun, Japan
    • Shizuoka Cancer Center
  • Yokohama, Japan
    • Kanagawa Cancer Center
• South Korea
  • Daegu, South Korea
    • Kyungpook National University Chilgok Hospital
  • Goyang-si, South Korea
    • National Cancer Center
  • Seongnam, South Korea
    • Seoul National University Bundang Hospital
  • Seoul, South Korea
    • Asan Medical Center
  • Seoul, South Korea
    • Samsung Medical Center
  • Seoul, South Korea
    • Seoul National University Hospital
  • Seoul, South Korea
    • Severance Hospital, Yonsei University Health System
• Spain
  • Barcelona, Spain
    • Hospital Clinic de Barcelona
  • Barcelona, Spain
    • Hospital del Mar
  • Barcelona, Spain
    • Hospital HM Nou Delfos
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron - VHIR
  • Córdoba, Spain
    • Hospital Universitario Reina Sofia
  • L'Hospitalet de Llobregat, Spain
    • ICO L'Hospitalet - Hospital Duran i Reynals
  • Madrid, Spain
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain
    • Centro Integral Oncológico Clara Campal
  • Madrid, Spain
    • Hospital Universitario Fundacion Jimenez Diaz
  • Madrid, Spain
    • Hospital Universitario Quironsalud Madrid - NEXT Oncology
  • Santiago de Compostela, Spain
    • Complejo Hospitalario Universitario de Santiago
  • Seville, Spain
    • Hospital Universitario Virgen del Rocio
• United States
  • California
    • Encinitas, California, United States, 92024
      • California Cancer Associates for Research & Excellence, Inc.
    • Fresno, California, United States, 93720
      • California Cancer Associates for Research & Excellence, Inc.
  • Rhode Island
    • Providence, Rhode Island, United States, 02903
      • Rhode Island Hospital
  • Texas
    • Dallas, Texas, United States, 75230
      • Mary Crowley Cancer Research
    • Houston, Texas, United States, 77030
      • MD Anderson Cancer Center - Oncology
    • San Antonio, Texas, United States, 78229
      • Next Oncology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: M9140	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.; Other Names: Precemtabart tocentecan; Drug: M9140; M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.; Other Names: Precemtabart tocentecan
Experimental: Part 2A: M9140	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.; Other Names: Precemtabart tocentecan; Drug: M9140; M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.; Other Names: Precemtabart tocentecan
Experimental: Part 2B: M9140	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.; Other Names: Precemtabart tocentecan; Drug: M9140; M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.; Other Names: Precemtabart tocentecan
Experimental: Part 2C: M9140 + Bevacizumab +/-Capecitabine	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.; Other Names: Precemtabart tocentecan; Drug: Bevacizumab; Bevacizumab will be administered intravenously as per standard of care.; Drug: Capecitabine; Capecitabine will be administered orally as per standard of care.; Drug: M9140; M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.; Other Names: Precemtabart tocentecan
Experimental: Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab	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.; Other Names: Precemtabart tocentecan; Drug: M9140; M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.; Other Names: Precemtabart tocentecan; Drug: 5-fluorouracil (5-FU); 5-FU will be administered intravenously as per standard of care.; Drug: Folinic acid; Folinic acid will be administered intravenously as per standard of care.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)	up to 4 months
Part 1: Recommended Dose Expansion (RDE) of M9140	up to 4 months
Part 2A: Number of Participants with Adverse Events (AEs)	up to 8 months
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
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
Parts 2B, 2C and 2D: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)	up to 8 months

Secondary Outcome Measures

Outcome Measure	Time Frame
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
Parts 1 and 2A: Change from Baseline in QTc (ΔQTc) Interval	Part 1: baseline, up to 4 months; Part 2: baseline up to 8 months
Part 2A: Overall Survival	Time from first study treatment to planned assessment at approximately 8 months
Part 2A: Number of Participants with Symptomatic Adverse Events (AEs)	up to 8 months
Parts 1, 2A, 2B, 2C and 2D: Pharmacokinetic (PK) Plasma Concentrations of M9140	Part 1: Pre-dose up to 4 months; Part 2: Pre-dose up to 8 months
Parts 1, 2A, 2B, 2C and 2D: Number of Participants with Anti-Drug Antibodies (ADA) Against M9140	Part 1: up to 4 months; Part 2: up to 8 months
Parts 1, 2A, 2B, 2C and 2D: Levels of Titers of Anti-Drug Antibody (ADA) Against M9140	Part 1: up to 4 months; Part 2: up to 8 months
Parts 1, 2B, 2C: and 2D: 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
Parts 1, 2B, 2C and 2D: 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
Parts 2A, 2B, 2C and 2D: Time to Response	Time from first study treatment to planned assessment at approximately 8 months
Parts 1, 2A, 2B, 2C and 2D: 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
Parts 2A, 2B, 2C and 2D: Number of Participants with Disease Control	At Week 12

Collaborators and Investigators

• Sponsor: EMD Serono Research & Development Institute, Inc.
• Collaborators: Merck KGaA, Darmstadt, Germany
• Investigators: Study Director: Medical Responsible, EMD Serono Research & Development Institute, Inc.

Publications and helpful links

General Publications

• Kopetz S, Boni V, Kato K, Raghav KPS, Vieito M, Pallis A, Habermehl C, Siddiqui A, Courlet P, Sloot W, Raab-Westphal S, Hart F, Rodriguez-Rivera I. Precemtabart tocentecan, an anti-CEACAM5 antibody-drug conjugate, in metastatic colorectal cancer: a phase 1 trial. Nat Med. 2025 Oct;31(10):3504-3513. doi: 10.1038/s41591-025-03843-z. Epub 2025 Jul 30.
• Sloot WN, Bertotti E, Onidi M, Paoletti A, Salve I, Tavano P, Vigna E, Mueller G. The Nonclinical Safety Assessment of a Novel Anti-CEACAM5 Antibody Exatecan Conjugate Predicts a Low Risk for Interstitial Lung Disease (ILD) in Patients-The Putative Mechanism Behind ILD. Int J Toxicol. 2025 Mar-Apr;44(2):153-169. doi: 10.1177/10915818241306039. Epub 2025 Jan 4.

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): August 4, 2022
• Primary Completion (Estimated): October 23, 2026
• Study Completion (Estimated): October 23, 2026

Study Registration Dates

• First Submitted: July 15, 2022
• First Submitted That Met QC Criteria: July 15, 2022
• First Posted (Actual): July 19, 2022

Study Record Updates

• Last Update Posted (Actual): July 30, 2026
• Last Update Submitted That Met QC Criteria: July 29, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colonic Diseases; Colorectal Neoplasms; Amino Acids, Peptides, and Proteins; Proteins; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Uracil; Pyrimidinones; Coenzymes; Deoxyribonucleosides; Capecitabine; Bevacizumab; Fluorouracil; Leucovorin
• Other Study ID Numbers: MS202329_0001; 2022-500508-23-00 (Other Identifier: EU CTIS); jRCT2031220313 (Other Identifier: JRCT (Japan))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

IPD Plan Description

IPD will not be shared for Phase I interventional or observational studies.

Further information on how to request data can be found on our website bit.ly/IPD21

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No