Metastatic Colorectal Cancer
Conditions
Keywords
Metastatic disease, Immunotherapy, Liver metastasis, Mismatch-repair-proficient, Antibody targeting, Colorectal Cancer, CANTOR
Brief summary
The main purpose of this study is to evaluate the safety and efficacy of novel study interventions and combinations in participants with Colorectal Cancer (CRC).
Detailed description
This is a Phase II, platform, open-label, multi-drug, multicenter, global study. This is a modular study, that includes a master protocol and substudies. Partcipants will be randomised to one of the following intervention groups: * Volrustomig + FOLFIRI + bevacizumab group (Arm A) * FOLFIRI + bevacizumab group (Arm B) The substudy will evaluate the effects of volrustomig in combination with FOLFIRI (irinotecan, 5-FU, and leucovorin) and bevacizumab versus FOLFIRI and bevacizumab only in participants with Mismatch-repair-proficient (pMMR)/Microsatellite stable (MSS) metastatic CRC (mCRC) in the absence of liver metastases and who have not received previous systemic treatment for advanced or metastatic disease.
Interventions
DRUGVolrustomig
Volrustomig will be administered as intravenous (IV) infusion.
FOLFIRI will be administered as IV infusion.
DRUGBevacizumab
Bevacizumab will be administered as IV infusion.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 130 Years
Healthy volunteers
No
Inclusion criteria
Overall Inclusion Criteria: * Histopathologically confirmed colorectal adenocarcinoma. * Provision of FFPE tumor sample collected as per SoC. * Presence of measurable disease by RECIST 1.1 criteria. * ECOG performance status of 0 or 1. * Life expectancy ≥ 12 weeks at the time of screening. Substudy Inclusion Criteria: * No radiological evidence of liver metastasis. * No prior systemic therapy for mCRC, except for neoadjuvant/adjuvant chemotherapy where, \> 6 months have elapsed between completion of therapy and documented date of diagnosis of recurrent or metastatic disease. * Known pMMR/MSS status (only pMMR/MSS mCRC allowed). * Adequate organ and bone marrow function * Body weight \> 35 kg at screening and at randomization. * Contraceptive use by participants should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Overall
Exclusion criteria
* Central nervous system metastases or spinal cord compression * Known history of severe allergy to any monoclonal antibody or study intervention. * Any unresolved toxicity CTCAE Grade ≥ 2 from a previous anticancer therapy. * History of another primary malignancy. Substudy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Approximately 3 years | PFS is defined as the time from randomization until progression per Response Evaluation Criteria in Solid Tumours, Version 1.1 (RECIST 1.1) or death due to any cause. |
| Number of Participants with Adverse Events (AEs) | Approximately 3 years | Number of participants who received at least one dose of study treatment will be assessed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Approximately 3 years | OS is defined as the time from randomization until the date of death due to any cause. |
| Objective Response Rate (ORR) | Approximately 3 years | ORR is defined as the proportion of participants who have a confirmed complete response or confirmed partial response as per RECIST 1.1. |
| Disease Control Rate (DCR) | Approximately 3 years | DCR is defined as the percentage of participants who have a confirmed CR or PR or who have SD per RECIST 1.1 after randomization. |
| Duration of Response (DOR) | Approximately 3 years | DoR is defined as the time from the date of first documented confirmed response until date of documented progression per RECIST 1.1 or death due to any cause. |
| Time to second progression or death (PFS2) | Approximately 3 years | PFS2 is defined as the time from randomization to the earliest of the progression event, after first subsequent therapy, or death. |
| Maximum Observed Concentration (Cmax) | Approximately 3 years | Concentration of novel study intervention in serum and PK parameters as data allow (such as peak and trough concentrations) will be assessed. |
| Observed lowest concentration before the next dose is administered (Ctrough) | Approximately 3 years | Concentration of novel study intervention in serum and PK parameters as data allow (such as peak and trough concentrations) will be assessed. |
| Number of patients with positive Antidrug Antibodies (ADAs) | Approximately 3 years | The immunogenicity (ADAs) of novel study intervention in participants with CRC in the absence of liver metastases is investigated. |
Countries
Australia, Canada, China, France, Germany, Italy, Netherlands, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
Outcome results
None listed