A Phase I, Multicenter, Open-Label First in Human Study of Anti-CEACAM5 Antibody Drug Conjugate M9140 in Participants With Advanced Solid Tumors
Considering participating in a START clinical trial?
Study Summary
To evaluate M9140 in patients with solid tumors.
To evaluate the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in advanced solid tumors.
To evaluate the safety, tolerability, PK, and preliminary clinical activity of M9140 in locally advanced and metastatic colorectal cancer, gastric cancer, and gastroesophageal junction cancer.
To assess combinations in colorectal cancer with standard-of-care agents with alternative scheduling options.
Part 1 of this Phase 1 trial investigated the safety and preliminary clinical activity of M9140 monotherapy (Q3W; IV) in patients with 3L+ mCRC. In addition to CEACAM5 IHC from archival tissue, patient records/archival tissue were assessed for KRAS, NRAS, and BRAF mutations.
To assess the safety, tolerability, pharmacokinetics, and preliminary clinical activity of M9140 in patients with mCRC who had received ≥2 prior lines of treatment
To evaluate clinical activity, safety, and tolerability of precemtabart tocentecan
To evaluate precem-TcT at 2.8 mg/kg Q3W (n=29) and 2.4 mg/kg Q3W (n=31) in 3L+ pts with mCRC.
- 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
- Patients with confirmed LA/M CRC intolerant/refractory to or progressing after standard systemic therapies
- • ECOG PS ≤1
- • Patients with archived FFPE tumor tissue available. If archived tumor material not available, fresh
- biopsy required
- • Patients were not selected on the basis of CEACAM5 expression
- 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
Clinical Study Information for Healthcare Providers
By clicking the button below you will find in-depth information about this clinical trial, including study design, primary and secondary endpoints, and more. This information is intended for healthcare professionals seeking to review the scientific and operational aspects of the study.