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RecruitingInterventionalPhase 1

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)

NCT ID: NCT05464030Sponsor: EMD Serono Research & Development Institute, Inc.Last updated: 2026-05-22

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

Arms & interventions

  • DrugM9140

    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.

  • DrugM9140

    M9140 will be further investigated in part 2 of the study and includes dose optimization, an alternative administration regimen and combination regimen.

  • DrugBevacizumab

    Bevacizumab will be administered intravenously as per standard of care.

  • DrugCapecitabine

    Capecitabine will be administered orally as per standard of care.

  • Drug5-fluorouracil (5-FU)

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

  • DrugFolinic acid

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

Outcome measures

Primary

  • Part 1: Number of Participants with Dose Limiting Toxicities (DLTs) and Adverse Events (AEs)

    Time frame: up to 4 months

  • Part 1: Recommended Dose Expansion (RDE) of M9140

    Time frame: up to 4 months

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

    Time frame: up to 8 months

  • Part 2A: Number of Participants with Adverse Events (AEs)

    Time frame: 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 frame: 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 frame: Time from first study treatment to planned assessment at approximately 8 months

Secondary

  • Parts 1, 2A, 2B, 2C and 2D: Pharmacokinetic (PK) Plasma Concentrations of M9140

    Time frame: 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

    Time frame: 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

    Time frame: 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)

    Time frame: Part 1: up to 4 months; Part 2: up to 8 months

  • Parts 1 and 2A: Change from Baseline in QTc (ΔQTc) Interval

    Time frame: Part 1: baseline, up to 4 months; Part 2: baseline 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 frame: 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 frame: 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 frame: 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 frame: Time from first study treatment to planned assessment at approximately 4 months and 8 months

  • Part 2A: Overall Survival

    Time frame: Time from first study treatment to planned assessment at approximately 8 months

  • Part 2A: Number of Participants with Symptomatic Adverse Events (AEs)

    Time frame: up to 8 months

  • Parts 2A, 2B, 2C and 2D: Number of Participants with Disease Control

    Time frame: At Week 12

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (6)

California Cancer Associates for Research & Excellence, Inc.

Encinitas, California, 92024

Completed

California Cancer Associates for Research & Excellence, Inc.

Fresno, California, 93720

Completed

Rhode Island Hospital

Providence, Rhode Island, 02903

Recruiting
Rimini Breakstone · Principal Investigator

Mary Crowley Cancer Research

Dallas, Texas, 75230

Recruiting
Minal Barve · Principal Investigator

MD Anderson Cancer Center - Oncology

Houston, Texas, 77030

Recruiting
Kanwal Raghav · Principal Investigator

NEXT Oncology

San Antonio, Texas, 78229

Recruiting
Ismael Rodriguez · Principal Investigator

References

  • 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.(PubMed)
  • 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.(PubMed)
Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01) | Cancerify