Colorectal Cancer
Conditions
Brief summary
KRAS is a common genetic mutation in tumors, and CRC is one of the tumors with a high KRAS mutation rate. The anti-tumor activity of KRAS G12C inhibitors combined with anti-EGFR anti-bodies have been proven in patients with advanced colorectal cancer, and one of them was approved for patients who have previously received standard treatment. However, Chinese patients still do not have access to these drugs. This study is to determine the efficacy and safety of KRAS G12C inhibitor JAB-21822 in combination with the second-line standard chemotherapy and bevacizumab in advanced colorectal cancer failed to standard therapy in Chinese population.
Detailed description
The study is aimed for patients with histologically confirmed advanced metastatic colorectal cancer with KRAS G12C mutation, patients enrolled will treated with JAB-21822 combined with standard second-line chemotherapy and bevacizumab until disease progression or intolerable toxicity or patient-initiated withdrawal from the study. Enrolled patients will undergo imaging assessments at baseline and every 6 weeks during the treatment period, the anti-tumor efficacy will be evaluated by the investigator according to RECIST v1.1. Safety assessment included vital signs, haematology, blood biochemistry and urinalysis and will be monitored regularly during the study period during treatment. Any discomfort experienced by the patients after administration of the drug will also be recorded.
Interventions
DRUGJAB-21822
Tablet, oral, 800 mg/QD, until PD or intolerable toxicity
The second line standard chemotherapy regimen recommended by clinical practice
DRUGBevacizumab
5mg/kg every two weeks (according to the assessment by investigator)
Sponsors
Jian Li
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically (or cytologically) confirmed, unresectable metastatic colorectal cancer. * KRAS G12C mutation. * At least one measurable disease per RECIST v1.1; assessed within 28 days before first dose. * Subject have withdrawn from the first-line chemotherapy due to disease progression or unacceptable toxicity; if first-line chemotherapy and maintenance therapy were received, disease progression must within three months; first-line chemotherapy regimens do not limit the use of antiangiogenic agents. * Adequate bone marrow, liver and renal function. * ECOG performance status 0-1. * Informed consent has been signed.
Exclusion criteria
* Patients have received KRAS G12C inhibitors. * Patients have received a first-line treatment, which include fluoropyrimidine, oxaliplatin and irinotecan. * Patients who are pregnant or breastfeeding. * Life expectancy of less than 3 months. * Patients who had major surgery or significant trauma within 4 weeks prior to the first blood sample collection during the screening period, or expected to require major surgery during the study period. * Patients with active ulcers and gastrointestinal bleeding. * Prior history of interstitial lung disease or non-infectious pneumonia; history of active tuberculosis. * Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage. * Patients with clinically diagnosed autoimmune disease; HIV, HCV positive; HBV-DNA beyond the normal range of the laboratory; Acute CMV infection. * Patients with active central nervous system metastases requiring treatment. * Patients with other malignancies within five years. * Assessed by the investigator, patients who are unable or unwilling to comply with the requirements of the study protocol.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Time Frame: up to 1year | The percentage of patients with total number of Complete Response (CR) + total number of Partial Response (PR) per RECIST v1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) | Time Frame: up to 1 year | Defined as the time from date of study treatment to death due to any cause. |
| Progression-free Survival (PFS) | Time Frame: up to 1 year | Defined as the time from date of study treatment to disease progression radiological/clinical or death due to any cause, whichever occurs first. |
| Disease Control Rate (DCR) | Time Frame: up to 1 year | Defined as the percentage of patients whose best response are not Progressive Disease (PD) according to RECIST v1.1. |
| Duration of Response (DOR) | Time Frame: up to 1 year | Defined as the time between the first assessment of the tumor as a CR or PR and the first assessment as disease progression (PD) or death from any cause. |
| Rate of treatment-related adverse events | Time Frame: up to 1 year | Number of patients with treatment-related adverse events as assessed by CTCAE v5.0. |
Countries
China
Outcome results
None listed