Clinical Trials/NCT05464030

NCT05464030

Recruiting

Phase 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)

EMD Serono Research & Development Institute, Inc.38 sites in 5 countries200 target enrollmentAugust 4, 2022

ConditionsColorectal Cancer

InterventionsM9140 Bevacizumab Capecitabine 5-fluorouracil (5-FU)Folinic acid

DrugsM9140 Bevacizumab Capecitabine 5-fluorouracil (5-FU)Folinic acid

Overview

Phase: Phase 1
Intervention: M9140
Conditions: Colorectal Cancer
Sponsor: EMD Serono Research & Development Institute, Inc.
Enrollment: 200
Locations: 38
Primary Endpoint: Part 2A: Number of Participants with Adverse Events (AEs)
Status: Recruiting
Last Updated: last month

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

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

Registry

clinicaltrials.gov

Start Date

August 4, 2022

End Date

February 26, 2027

Last Updated

last month

Study Type

Interventional

Study Design

Sequential

Sex

All

Investigators

Sponsor

EMD Serono Research & Development Institute, Inc.

Responsible Party

Sponsor

Eligibility Criteria

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

Arms & Interventions

Part 1: M9140

Intervention: M9140

Part 2A: M9140

Intervention: M9140

Part 2B: M9140

Intervention: M9140

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Intervention: M9140

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Intervention: Bevacizumab

Part 2C: M9140 + Bevacizumab +/-Capecitabine

Intervention: Capecitabine

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

Intervention: M9140

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

Intervention: 5-fluorouracil (5-FU)

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

Intervention: Folinic acid

Outcomes

Primary Outcomes

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

Time Frame: up to 8 months

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: 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 Outcomes

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)