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)
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
Study locations (6)
California Cancer Associates for Research & Excellence, Inc.
Encinitas, California, 92024
California Cancer Associates for Research & Excellence, Inc.
Fresno, California, 93720
Rhode Island Hospital
Providence, Rhode Island, 02903
Mary Crowley Cancer Research
Dallas, Texas, 75230
MD Anderson Cancer Center - Oncology
Houston, Texas, 77030
NEXT Oncology
San Antonio, Texas, 78229
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)