Metastatic Colorectal Cancer
Conditions
Keywords
CEACAM5, Antibody-drug conjugate, Exatecan, M9140, Precem-TcT
Brief summary
This study aims to address the unmet medical need of participants with metastatic colorectal cancer (mCRC) who have previously been treated with irinotecan, oxaliplatin, a fluoropyrimidine, and bevacizumab, by demonstrating an overall survival prolongation with precemtabart tocentecan (Precem-TcT) as single agent or Precem-TcT in combination with bevacizumab compared to trifluoride/tipiracil (FTD-TPI) plus bevacizumab.
Interventions
DRUGPrecemtabart tocentecan
Precem-TcT, administered, once every 3 weeks intravenously, on Day 1 of each 21-day cycle.
DRUGBevacizumab
Bevacizumab, administered intravenously every 3 weeks on Day 1 of each 21-day cycle or every 2 weeks on Day 1 and Day 15 of each 28-day cycle.
DRUGTrifluridine/Tipiracil (FTD-TPI)
FTD-TPI, tablet, administered orally twice daily, on Days 1 to 5 and Days 8 to 12 of each 28-day cycle.
Sponsors
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
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 metastatic colorectal cancer, who were intolerant to, or whose disease was refractory to, or progressed after standard systemic therapies and no more than 2 previous systemic treatment regimens in the metastatic setting. * Participants must have received and progressed on no more than 2 previous systemic treatment regimens in the metastatic setting * Eastern Cooperative Oncology Group (ECOG) performance status less than equal to 1 * Participants must be able to swallow oral tablets, and to comply with the study requirements for all scheduled evaluations * Other protocol defined inclusion criteria may apply
Exclusion criteria
* If Adverse Events related to previous therapies have not recovered to less than Grade 1 by National Cancer Institute - Common Terminology Criteria for Adverse Events version 6.0 * Participant has a history of additional malignancy within 3 years before randomization * Participants with known brain metastases * Abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months prior to randomization * Participants with ileus of more than Grade 1, or chronic inflammatory bowel disease (example ulcerative colitis, Crohn's disease) and/or bowel obstruction, or participants with chronic gastrointestinal disorders that, in the Investigator's opinion, might significantly interfere with proper absorption of the study treatments * Other protocol defined
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Arm 1, 2 and 3: Overall Survival | Time from date of randomization to death, assessed approximately up to average of 19 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Arm 1 and Arm 2: Overall Survival | Time from date of randomization to death, assessed approximately up to average of 19 months | — |
| Progression Free Survival (PFS) | Time from randomization to the first occurrence of disease progression or death, whichever occurs first (assessed up to average of 19 months) | — |
| Objective Response (OR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator | Up to average of 19 months | — |
| Duration of Response as Assessed by Investigator | Time from first documentation of objective response to PD or death (assessed up to average of 19 months) | — |
| Number of Participants with Adverse Events (AEs) and Treatment Related Adverse Events | Up to average of 19 months | — |
| Observed Concentration at End of Infusion (CEOI) Period | At end of infusion on Cycle 1 Day 1 and Cycle 3 Day 1 (Arm 1 and Arm 2 only; each cycle is for 21 days) | — |
| Concentration Observed at the end of a Dosing Interval Immediately Before next Dosing (Ctrough) | At end of dosing interval on Cycle1Day1,Cycle2Day1,Cycle3Day1,Cycle4Day1, Cycle5Day1,Cycle6Day1,Cycle7Day1 until treatment discontinuation(assessed up to average of 19months (Arm 1 and Arm 2 only; each cycle is for 21 days) | — |
| Number of Participants with Anti-Drug Antibody as measured by ADA assay | Predose(-4to0 hours)on Cycle1Day1,Cycle2 Day1,Cycle 3Day1,Cycle4Day1, Cycle8Day1;thereafter every 4cycles until treatment discontinuation(assessed up to average of 19 months) (Arm 1 and Arm 2 only; each cycle is for 21 days) | — |
| Change from Baseline in Global Health Status, Physical, and Role Functioning Subscale Scores of European Organization for research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ-C30) | Baseline, Cycle 1 Day 1 and Day 1 of every new cycle until treatment discontinuation (assessed up to average of 19 months). | EORTC QLQ-C30 is a 30-question tool used to assess the overall quality of life (QoL) in cancer participants. It consists of 15 domains: 1 global health status (GHS) scale, 5 functional scales (Physical, role, cognitive, emotional, social), and 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact. The EORTC QLQ-C30 GHS/QoL score ranges from 0 to 100; High score indicates better GHS/QoL. Score 0 represents: very poor physical condition and QoL. Score 100 represents: excellent overall physical condition and QoL. |
Countries
Argentina, Australia, Austria, Belgium, Canada, China, France, Germany, Hong Kong, Japan, Poland, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTUS Medical Information
CONTACTCommunication Center
STUDY_DIRECTORMedical Responsible
EMD Serono Research & Development Institute, Inc.
Outcome results
None listed