Colorectal Cancer
Conditions
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
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.
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.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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: Number of Participants with 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
| Measure | Time frame |
|---|---|
| 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, 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: 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 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 |
| 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 |
| 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 |
| Parts 2A, 2B, 2C and 2D: Number of Participants with Disease Control | At Week 12 |
Countries
Canada, Japan, South Korea, Spain, United States
Contacts
CONTACTUS Medical Information
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
EMD Serono Research & Development Institute, Inc.
Outcome results
None listed