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

NCT05464030 | Active Not Recruiting Phase 1 FDA Drug

• 3 other identifiers: MS202329_00012022-500508-23-00jRCT2031220313
• Study Type: interventional
• Target: 220
• Locations: 5 countries
• Sites: 35

Brief 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

Conditions

Colorectal Cancer

Outcome Measures

Primary Outcomes (6)

• 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

• Parts 2B, 2C and 2D: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)

  up to 8 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

Secondary Outcomes (12)

• 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 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

Study Arms (5)

Part 1: M9140

EXPERIMENTAL

Drug: M9140

Part 2A: M9140

EXPERIMENTAL

Drug: M9140

Part 2B: M9140

EXPERIMENTAL

Drug: M9140

Part 2C: M9140 + Bevacizumab +/-Capecitabine

EXPERIMENTAL

Drug: M9140; Drug: Bevacizumab; Drug: Capecitabine

Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab

EXPERIMENTAL

Drug: M9140; Drug: 5-fluorouracil (5-FU); Drug: Folinic acid

Interventions

5-fluorouracil (5-FU) DRUG

5-FU will be administered intravenously as per standard of care.

Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab

Folinic acid DRUG

Folinic acid will be administered intravenously as per standard of care.

Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab

M9140 DRUG

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.

Also known as: Precemtabart tocentecan

Part 1: M9140

Bevacizumab DRUG

Bevacizumab will be administered intravenously as per standard of care.

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Capecitabine DRUG

Capecitabine will be administered orally as per standard of care.

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (35)

California Cancer Associates for Research & Excellence, Inc.

Encinitas, California, 92024, United States

Location

California Cancer Associates for Research & Excellence, Inc.

Fresno, California, 93720, United States

Location

Rhode Island Hospital

Providence, Rhode Island, 02903, United States

Location

Mary Crowley Cancer Research

Dallas, Texas, 75230, United States

Location

MD Anderson Cancer Center - Oncology

Houston, Texas, 77030, United States

Location

NEXT Oncology

San Antonio, Texas, 78229, United States

Location

The Ottawa Hospital Cancer Centre

Ottawa, Canada

Location

University Health Network - Princess Margaret Cancer Centre

Toronto, Canada

Location

National Cancer Center Hospital - Dept of Gastroenterology

Chūōku, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, Japan

Location

Saitama Cancer Center

Kitaadachi-gun, Japan

Location

Cancer Institute Hospital of JFCR

Kōtoku, Japan

Location

Aichi Cancer Center Hospital

Nagoya, Japan

Location

Kindai University Hospital

Osakasayama-shi, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Japan

Location

Kanagawa Cancer Center

Yokohama, Japan

Location

Kyungpook National University Chilgok Hospital

Daegu, South Korea

Location

National Cancer Center

Goyang-si, South Korea

Location

Seoul National University Bundang Hospital

Seongnam, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Hospital Clinic de Barcelona

Barcelona, Spain

Location

Hospital del Mar

Barcelona, Spain

Location

Hospital HM Nou Delfos

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - VHIR

Barcelona, Spain

Location

Hospital Universitario Reina Sofia

Córdoba, Spain

Location

ICO l'Hospitalet - Hospital Duran i Reynals

L'Hospitalet de Llobregat, Spain

Location

Centro Integral Oncologico Clara Campal

Madrid, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, Spain

Location

Hospital Universitario Fundacion Jimenez Diaz

Madrid, Spain

Location

Hospital Universitario Quironsalud Madrid - NEXT Oncology

Madrid, Spain

Location

Complejo Hospitalario Universitario de Santiago

Santiago de Compostela, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Related Publications (2)

• 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.

  PMID: 40739424 RESULT

• 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.

  PMID: 39754485 DERIVED

Related Links

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

MeSH Terms

Conditions

Colorectal Neoplasms

Interventions

Bevacizumab; Capecitabine; Fluorouracil; Leucovorin

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Uracil; Pyrimidinones; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes

Study Officials

• Medical Responsible

  EMD Serono Research & Development Institute, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 15, 2022
• First Posted: July 19, 2022
• Study Start: August 4, 2022
• Primary Completion (Estimated): October 23, 2026
• Study Completion (Estimated): October 23, 2026
• Last Updated: July 30, 2026

Record last verified: 2026-07

Data Sharing

• IPD Sharing: Will not share

Locations

KR (7); US (6); ES (12); CA (2); JP (8)