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

Merck KGaA (EMD Serono)

Status and phase: Enrolling; Phase 1

Conditions: Colorectal Cancer

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

Study type: Interventional

Funder types: Industry

Identifiers

NCT05464030

2022-500508-23-00 (Other Identifier)

MS202329_0001

Details and patient eligibility

About

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

Enrollment: 200 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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200 participants in 5 patient groups

Part 1: M9140

Experimental group

Treatment:

Drug: M9140

Drug: M9140

Part 2A: M9140

Experimental group

Treatment:

Drug: M9140

Drug: M9140

Part 2B: M9140

Experimental group

Treatment:

Drug: M9140

Drug: M9140

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Experimental group

Treatment:

Drug: Capecitabine

Drug: M9140

Drug: Bevacizumab

Drug: M9140

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

Experimental group

Treatment:

Drug: 5-fluorouracil (5-FU)

Drug: Folinic acid

Drug: M9140

Drug: M9140