Metastatic Colorectal Cancer
Conditions
Brief summary
This study is a multicenter, dose-escalating phase Ib clinical study to evaluate the safety and tolerability of GB226 in combination with fruquintinib in the treatment of mCRC, evaluate the pharmacokinetic characteristics of GB226 in combined therapy, evaluate immunogenicity of GB226, and explore the antitumor activity of GB226 in combination with fruquintinib in the treatment of mCRC.
Interventions
DRUGGeptanolimab Injection
GB226 3mg/kg, q2w, iv.
DRUGFruquintinib
Fruquintinib 3 or 4 or 5mg,qd,po. 3 weeks-on, 1 week-off
Sponsors
Hutchison Medipharma Limited
Genor Biopharma Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
Patients who meet the following criteria can be enrolled in this study: 1. Aged 18 to 75 years, males or females; 2. Understand the study procedures and contents, and voluntarily sign the written informed consent form; 3. Patients with histologically/pathologically confirmed colorectal cancer; 4. Patients with metastatic colorectal cancer, who failed to respond to the previous first-line treatment or above. Treatment failure refers to disease progression or intolerable toxicity after ≥1 cycle of treatment, or relapse during adjuvant or neoadjuvant chemotherapies period or within 6 months after the end of treatment; 5. ECOG score of 0-1; 6. Life expectancy≥3 months; 7. There is at least one measurable and evaluable tumor lesion (in accordance with RECIST1.1 criteria); 8. Systemic chemotherapy, targeted therapies or other anti-tumor biotherapy (tumor vaccine, cytokine or growth factor aimed at controlling tumor) are completed at least 4 weeks before the first dose of investigational product (the oral fluorouracil is discontinued at least 2 weeks ago); systemic or local palliative radiotherapy is completed at least 4 weeks ago; no anti-angiogenic small molecular target drugs are previously received; 9. Systemic corticosteroids (prednisone \> 10mg/day or equivalent dose) is discontinued at least 2 weeks before the use of the first investigational product; 10. The major surgery requiring general anesthesia must be completed at least 8 weeks before the use of the first investigational product; surgery requiring local anesthesia/epidural anesthesia must be completed at least 4 weeks before the use of the first investigational product; 11. Routine blood tests require hemoglobin (HGB) ≥90g/L (no transfusion is allowed within 14 days before routine blood tests at baseline), neutrophil count (ANC)≥1.5×109/L (received no supportive treatment with recombinant human granulocyte colony stimulating factor within 14 days before routine blood tests at baseline), platelet ≥100×109/L (received no supportive treatment such as recombinant human thrombopoietin (TPO) or transfusion within 14 days before routine blood tests at baseline); 12. Serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min (calculated based on Cockcroft-Gault formula), and urinary protein ˂ 2+ or ˂1.0g/L; For patients with baseline urinary protein ≥ 2+ or ≥ 1.0g/L, quantitative test of 24h urinary protein will be performed and will be enrolled only when the result ≤ 1.0g/L is obtained. 13. Total bilirubin ≤1.5×ULN (unless it is confirmed to have Gilbert's Syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (AST and/or ALT≤5×ULN is allowed for patients with hepatic metastasis); 14. Thyroid function variables: thyroid-stimulating hormone (TSH) and free thyroxine (FT3/FT4) are within the normal range; if TSH is not within the normal range, but FT3/FT4 is within the normal range, the subjects can be enrolled. 15. The adverse reactions caused by the previous treatment should recover to grade 1 and below before enrollment (except alopecia and ≤ grade 2 neurological toxicity caused by chemotherapy drugs); 16. Female subjects who are confirmed not pregnant within 7 days before administration; males or females should agree to adopt medically confirmed effective contraceptive measures during the entire study period and within 6 months after the end of this study. 17. Patients can receive follow-up visits as scheduled, well communicate with the investigators and complete the study as required by the study.
Exclusion criteria
Any patient fulfilling any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Event | up to 52 weeks | Adverse Event |
| Dose Limited Toxicity,DLT | up to 52 weeks | To evaluate the safety of GB226 as defined by dose limited toxicity in patients with metastatic colorectal cancer. |
| Extended period recommended dose,RDE | up to 52 weeks | To evaluate the safety of GB226 as defined by extended period recommended dose in patients with metastatic colorectal cancer. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| R C,trough | up to 52 weeks | R C,trough |
| Objective Response Rate, ORR | up to 52 weeks | To evaluate the efficacy of GB226 as defined by objective response rate in patients with metastatic colorectal cancer. |
| Disease control rate (DCR) | up to 52 weeks | To evaluate the efficacy of GB226 as defined by overall response rate, in patients with metastatic colorectal cancer. |
| T max | up to 52 weeks | T max |
| Progression-free survival, PFS | up to 52 weeks | To evaluate the efficacy of GB226 as defined by progression-free survival in patients with metastatic colorectal cancer. |
| Overall survival, OS | up to 52 weeks | To evaluate the duration from the first administration to death because of any reason in patients with metastatic colorectal cancer. |
| Antidrug antibody, ADA | up to 52 weeks | Antidrug antibody, ADA |
| Duration of response, DOR | up to 52 weeks | To evaluate the duration of response (DOR) of GB242 in patients with metastatic colorectal cancer. |
| C max | up to 52 weeks | C max |
| C ss,min | up to 52 weeks | C ss,min |
Countries
China
Contacts
Primary ContactShawn Yu, Master
Outcome results
None listed