Anti-CEACAM5 ADC M9140 in Advanced Solid Tumors (PROCEADE-CRC-01)
- Conditions
- Colorectal Cancer
- Interventions
- Registration Number
- NCT05464030
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 200
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab 5-fluorouracil (5-FU) - Part 2B: M9140 M9140 - Part 2C: M9140 + Bevacizumab +/-Capecitabine M9140 - Part 1: M9140 M9140 - Part 2A: M9140 M9140 - Part 2C: M9140 + Bevacizumab +/-Capecitabine Bevacizumab - Part 2C: M9140 + Bevacizumab +/-Capecitabine Capecitabine - Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab M9140 - Part 2D: M9140 + 5-fluorouracil + Folinic acid + Bevacizumab Folinic acid -
- Primary Outcome Measures
Name Time Method Part 2A: Number of Participants with Adverse Events (AEs) up to 8 months 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: 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 Outcome Measures
Name Time Method 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 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, 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 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: Change from Baseline in QTc (ΔQTc) Interval 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 from first study treatment throughout the study duration until progressive disease or death up to approximately 4 months and 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
Trial Locations
- Locations (34)
California Cancer Associates for Research & Excellence, Inc.
🇺🇸Fresno, California, United States
Rhode Island Hospital
🇺🇸Providence, Rhode Island, United States
Mary Crowley Cancer Research
🇺🇸Dallas, Texas, United States
MD Anderson Cancer Center - Oncology
🇺🇸Houston, Texas, United States
NEXT Oncology
🇺🇸San Antonio, Texas, United States
The Ottawa Hospital Cancer Centre
🇨🇦Ottawa, Canada
University Health Network - Princess Margaret Cancer Centre
🇨🇦Toronto, Canada
National Cancer Center Hospital - Dept of Gastroenterology
🇯🇵Chuo-ku, Japan
National Cancer Center Hospital East
🇯🇵Kashiwa-shi, Japan
Saitama Cancer Center
🇯🇵Kitaadachi-gun, Japan
Cancer Institute Hospital of JFCR
🇯🇵Koto-ku, Japan
Aichi Cancer Center Hospital
🇯🇵Nagoya-shi, Japan
Kindai University Hospital
🇯🇵Osakasayama-shi, Japan
Seoul National University Bundang Hospital
🇰🇷Seongnam, Korea, Republic of
Samsung Medical Center
🇰🇷Seoul, Korea, Republic of
Shizuoka Cancer Center
🇯🇵Sunto-gun, Japan
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Severance Hospital, Yonsei University Health System
🇰🇷Seoul, Korea, Republic of
Kanagawa Cancer Center
🇯🇵Yokohama-shi, Japan
Kyungpook National University Chilgok Hospital
🇰🇷Daegu, Korea, Republic of
National Cancer Center
🇰🇷Goyang-si, Korea, Republic of
Asan Medical Center
🇰🇷Seoul, Korea, Republic of
Hospital Clinic de Barcelona
🇪🇸Barcelona, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital HM Nou Delfos
🇪🇸Barcelona, Spain
Hospital Universitari Vall d'Hebron - VHIR
🇪🇸Barcelona, Spain
Hospital Universitario Reina Sofia
🇪🇸Cordoba, Spain
ICO l'Hospitalet - Hospital Duran i Reynals
🇪🇸L'Hospitalet de Llobregat, Spain
Centro Integral Oncologico Clara Campal
🇪🇸Madrid, Spain
Hospital Universitario 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Fundacion Jimenez Diaz
🇪🇸Madrid, Spain
Hospital Universitario Quironsalud Madrid - NEXT Oncology
🇪🇸Madrid, Spain
Complejo Hospitalario Universitario de Santiago
🇪🇸Santiago de Compostela, Spain
Hospital Universitario Virgen del Rocio
🇪🇸Sevilla, Spain