Colorectal Cancer
Conditions
Brief summary
This study is an open, multi-center, phase II study, aiming to evaluate the safety, tolerability and efficacy of AMT-676 combined with 5-fluorouracil, leucovorin, bevacizumab (or cetuximab) in participants with advanced colorectal cancer, and to assess the PK(Pharmacokinetic) characteristics and immunogenicity of AMT-676.
Interventions
DRUGAMT-676
Patients will get different dose levels treatment of AMT-676. AMT-676 will be Administered as an intravenous (IV) infusion every 2 weeks (Q2W) .
DRUG5-FU
5-FU 400 mg/m\^2 IV bolus on day 1, followed by 1200 mg/m\^2/day x 2 days (total 2400 mg/m\^2 over 46-48 hours) IV continuous infusion, q2w
DRUGLeucovorin
Leucovorin 400 mg/m\^2 IV day 1, q2w
DRUGBevacizumab
Bevacizumab 5 mg/kg IV, day 1
DRUGCetuximab
Cetuximab 500 mg/m\^2 IV over 2 hours, day 1, q2w
DRUGIrinotecan
Irinotecan 180 mg/m\^2 IV, day 1
DRUGOxaliplatin
Oxaliplatin 85 mg/m\^2 IV, day 1
Sponsors
Multitude Therapeutics Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Patients must be willing and able to sign the ICF, and to adhere to the study visit schedule and other protocol requirements * Patients with pathologically confirmed, unresectable advanced colorectal adenocarcinoma * Patients must have at least one measurable lesion as per RECIST version 1.1 * Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 * Life expectancy ≥6 months * Patients must have adequate organ function * Male and female individuals with child bearing potential must agree to take effective contraceptive measures from the moment they sign the informed consent form until 6 months after the last administration of the study drug * WCBP(Women of Child-Bearing Potential) must have a negative serum pregnancy test within 7 days prior to first dose of the IMP * Male patients must agree not to donate sperm, and female patients must agree not to donate eggs, while on study treatment and for at least 3 months and 6 months, respectively, after the last dose of the IMP(Investigational Medicinal Product) * Availability of tumor tissue sample
Exclusion criteria
* Prior treatment with any same target * Systemic anti-neoplastic therapy within five half-lives or 21 days, whichever is shorter, prior to first dose of the IMP * Persistent toxicities from previous systemic anti-neoplastic treatments of Grade \>1 * Major surgery within 28 days prior to first dose of the IMP, or no recovery from side effects of such intervention, or a surgery is planned to be conducted within the expected participation period of the trial or within 4 weeks after the last administration of the drug * History of thromboembolic or cerebrovascular events during last 6 mouths * During the three months prior to the first administration of the drug, there were any life-threatening bleeding events, or grade 3 or higher gastrointestinal/venous variceal bleeding events that required blood transfusion, endoscopy, or surgical treatment. Or there were other diseases that the researchers believed posed a higher risk of bleeding or thrombosis during the study period * Has a history of interstitial lung disease (ILD)/pneumonitis that required steroids, or current ILD/pneumonitis, or suspected ILD/pneumonitis , or other lung disease significantly impacting lung function at baseline. * Any other concurrent diseases or conditions that could affect the research judgment or impede the completion of the research procedures and follow-up checks * Central nervous system (CNS) metastasis * Have a history of active or acute diverticulitis, abdominal abscess, gastrointestinal obstruction, fistula, or peritoneal cancer * Any evidence indicates severe or uncontrolled systemic diseases * Acute and/or clinically significant bacterial, fungal or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV). * Administration of a live vaccine within 28 days prior to the administration of the first dose of the IMP * Patients requiring concurrent treatment of strong/moderate inhibitors or strong inducers of cytochrome P450 3A4 or 1A2 enzyme (CYP3A or CYP1A2) within 2 weeks prior to the first dose and during the study treatment * Known or suspected severe allergy/hypersensitivity (resulting in treatment discontinuation) to monoclonal antibodies * Known or suspected intolerance to the components of the IMP * Concurrent participation in another investigational therapeutic clinical trial * Pregnant or breast-feeding females * Investigator determined that the trial participants who were not suitable to participate in this study for other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AE & SAE | 30 days after the last treatment | Type, incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
| MTD | 28 days after first dose | Maximum Tolerated Dose will be determined by DLTs |
| DLTs | 28 days after first dose | Incidence of dose limiting toxicities |
| ORR | through study completion, an average of 18 months | Overall response rate |
| PFS | through study completion, an average of 18 months | Progression-free survival |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cmax | From first dose to end of treatment, an average of 1 year | maximum concentration of the ADC, total antibody and free payload |
| Ctrough | From first dose to end of treatment, an average of 1 year | predose concentration of the ADC, total antibody and free payload |
| AUC | From first dose to end of treatment, an average of 1 year | Area Under the Curve of the ADC, total antibody and free payload |
| Specification of anti-drug antibodies | From first dose to end of treatment, an average of 1 year | — |
| Quantification of anti-drug antibodies | From first dose to end of treatment, an average of 1 year | — |
Countries
China
Contacts
CONTACTMinqi Guan
Outcome results
None listed