Colorectal Cancer
Conditions
Brief summary
To assess the safety and preliminary efficacy of TQB2930 and chemotherapy with or without bevacizumab in subjects with HER2-positive unresectable locally advanced or metastatic colorectal cancer (CRC).
Interventions
DRUGTQB2930 injection + Oxaliplatin injection + Capecitabine tablets + Bevacizumab injection
TQB2930 enhances the binding to HER2 protein on the surface of tumor cells and increases HER2 internalization by simultaneously targeting ECD2 and ECD4, two non-overlapping epitopes of HER2 protein, which in turn more effectively down-regulates HER2 protein on the surface of tumor cells and dually blocks HER2 signaling. Oxaliplatin can block DNA replication and transcription and induce tumor cell apoptosis. Capecitabine inhibits thymidylate synthase (TS) and interferes with DNA synthesis. Bevacizumab blocks Vascular Endothelial Growth Factor (VEGF) binding to receptors and inhibits tumor angiogenesis.
DRUGTQB2930 injection + Oxaliplatin injection + Capecitabine tablets
TQB2930 enhances the binding to HER2 protein on the surface of tumor cells and increases HER2 internalization by simultaneously targeting Extracellular Domain 2 (ECD2) and Extracellular Domain 4 (ECD4), two non-overlapping epitopes of HER2 protein, which in turn more effectively down-regulates HER2 protein on the surface of tumor cells and dually blocks HER2 signaling. Oxaliplatin can block DNA replication and transcription and induce tumor cell apoptosis. Capecitabine inhibits thymidylate synthase (TS) and interferes with DNA synthesis.
Sponsors
Chia Tai Tianqing Pharmaceutical Group Nanjing Shunxin Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects voluntarily participate in this study, sign the informed consent form, and have good compliance * Age: 18-75 years (including the boundary when signing the informed consent form) * Eastern Cooperative Oncology Group (ECOG) score: 0-1 * Expected survival of more than 3 months * Unresectable locally advanced or metastatic colorectal cancer diagnosed by histopathology/cytology * HER2 positive tested * Presence of at least one measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria * Subjects should agree to use contraception during the study and for 6 months after the end
Exclusion criteria
* Patients with previously confirmed Microsatellite Instability Microsatellite Instability-High Deficient Mismatch Repair (MSI-H/dMMR) * Presence of conditions affecting intravenous, venous blood sampling, or multiple factors affecting oral medications * Active inflammatory bowel disease within 28 days prior to first dose * Other malignancies within 5 years prior to the first dose or currently suffering from other malignancies * Unresolved toxicity greater than CTCAE Grade 1 due to any prior therapy * Major surgical treatment, significant traumatic injury within 28 days prior to the first dose or anticipation of major surgery during study treatment * Had wounds or fractures that had not been healed for a long time * Cerebrovascular accident, deep venous thrombosis and pulmonary embolism within 6 months prior to the first dose * Patients with a history of psychotropic substance abuse who cannot quit or have mental disorders * Subjects with any severe and/or uncontrolled disease * Known tumor-related carcinomatous meningitis with symptoms of brain metastases or symptom control for less than 4 weeks * Patients with imaging suggestive of tumor invasion of major blood vessels or fatal massive hemorrhage due to tumor rupture or invasion of major blood vessels judged by the investigator to be very likely to occur during the study * Failure to control serous effusions requiring repeated drainage * Local radiotherapy or 4. Bone marrow irradiation \> 30% for bone metastasis before the first medication * Known tumor-related spinal cord compression, weight-bearing bone pathological fracture, extensive bone metastasis, or uncontrollable tumor bone metastasis-related pain * Patients who have received chemotherapy, targeted therapy, immunotherapy or other systemic anti-tumor drug therapy before the first medication; * Received Chinese patent medicine treatment with anti-tumor indications in the package insert of National Medical Products Administration (NMPA) approved drugs before study treatment * History of live attenuated vaccination before the first dose or planned live attenuated vaccination during the study; * Previous history of severe allergy of unknown origin * According to the investigator's judgment, there are concomitant diseases that seriously endanger the subject's safety or affect the completion of the study, or the subject is considered unsuitable for other reasons
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recommended Phase 2 Dose | Baseline up to 21 days | It refers to the safe and effective dose range that can be used for phase II study determined through phase I clinical trial. |
| Adverse event (AE) | From the subject's signing of the informed consent form to 28 days after the last dose or the start of new anti-tumor therapy (whichever occurs first) | Incidence and severity of adverse events. |
| Objective Response Rate | Baseline up to 24 months | The proportion of patients achieving complete response and partial response among the total evaluable cases. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Half-life | Baseline up to 24 months | The time it takes for the concentration of a drug in the body (usually the plasma concentration) to decrease to half of its initial value. |
| Plasma concentration-time profiles | Baseline up to 24 months | Total area covered under the curve plotted with time as X-axis and plasma concentration as Y-axis. |
| Apparent clearance | Baseline up to 24 months | The rate at which the drug is cleared from the body. |
| Apparent terminal volume of distribution | Baseline up to 24 months | Describe the drug distribution in the body. |
| Trough plasma concentration | Baseline up to 24 months | Minimum plasma drug concentration level at the end of the dosing interval (before the next dosing). |
| Disease Control Rate | Baseline up to 24 months | The percentage of subjects with a complete response, partial response, or stable disease as determined by RECIST 1.1. |
| Duration Of Response | Baseline up to 24 months | The time from the first assessment of the tumor as a complete response or partial response to the first occurrence of disease progression or death from any cause. |
| Progression Free Survival | Baseline up to 24 months | Progression Free Survival (PFS) is defined as the length of time from the start of treatment until the disease progresses or the patient dies from any cause. |
| Overall Survival | Baseline up to 24 months | The time from the start of initial treatment to death from any cause. |
| Anti-Drug Antibodies (ADA) incidence | Baseline up to 24 months | Proportion of anti-drug antibody produced in the population of patients using the drug. |
Countries
China
Contacts
CONTACTRuihua Xu, Doctor
Outcome results
None listed