metastatic RAS wild-type colorectal cancer
Conditions
Interventions
Trial group:Becotatug + Cetuximab
Sponsors
Fudan University Shanghai Cancer Center
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Inclusion criteria
Inclusion criteria: 1. Volunteer to sign the informed consent form, fully understand and sign the informed consent (ICF) for this study; willing to follow and capable of completing all trial procedures; 2. No gender restriction, aged >=18 years (as of the day of signing the informed consent form); 3. Histologically or cytologically confirmed metastatic RAS wild-type colorectal cancer; 4. Patients should have received the following treatments: (1) previously received chemotherapy based on oxaliplatin and/or irinotecan; (2) received anti-vascular endothelial growth factor (VEGF) treatment or anti-epidermal growth factor receptor (EGFR) treatment for left-sided colorectal cancer; (3) for patients diagnosed with high microsatellite instability (MSI-H) or mismatch repair deficiency (dMMR), they also need to have received treatment with programmed death protein-1 (PD-1) or its ligand (PD-L1) inhibitors; (4) subjects without BRAF mutations. 5. According to the Response Evaluation Criteria in Solid Tumors (RECIST v1.1), subjects must have at least one measurable lesion (lesion with a longest diameter >=10mm). 6. Within 7 days before the first dose, physical condition score according to the Eastern Cooperative Oncology Group (ECOG) standard is 0 or 1. 7. Expected survival >=12 weeks. 8. Have appropriate organs and hematopoietic function (no blood transfusion or use of any cell growth factors within 14 days before the first use of study drugs), according to the following laboratory tests: (1) Neutrophil count (NEUT#) >=1.5×10^9/L; platelet count >=75×10^9/L; (2) Hemoglobin >=85g/L; (3) Serum creatinine =1.5 times the upper limit of normal (ULN); (4) AST, ALT <=2.5 times ULN (can be relaxed to <=5 times ULN for patients with liver metastasis); (5) Total bilirubin (TBIL) <=1.5 times ULN; (6) International normalized ratio (INR) <=1.5 times ULN, activated partial thromboplastin time (APTT) <=1.5 times ULN (except for patients undergoing anticoagulant therapy). 9. For female patients with reproductive capacity, blood pregnancy test results should be negative within 7 days before treatment; Female subjects of childbearing age and male subjects whose partners are female subjects of childbearing age must agree to use highly effective contraceptive methods (such as oral contraceptives, intrauterine devices, abstinence, or barrier contraception combined with spermicide) for contraception from the time they sign the informed consent form until one year after the last administration of study medication. 10. Subjects must have good compliance.
Exclusion criteria
Exclusion criteria: 1. Presence of >= Grade 2 peripheral neuropathy (based on CTCAE 5.0); 2. Expected to require surgery or any other form of systemic or local anti-tumor treatment during the study period; 3. Having undergone any of the following treatments: (1) Previously receiving antibody-conjugated drugs loaded with methotrexate; (2) Receiving study drugs from other clinical trials within 28 days prior to the first dose; (3) Receiving radiotherapy within 28 days prior to the first dose or palliative radiotherapy for bone metastases within 2 weeks; (4) Receiving any anti-tumor drugs within 3 weeks prior to the first dose (whichever is shorter, with a washout period of >=14 days for oral fluoropyrimidine derivatives, folinic acid derivatives, and weekly intensive paclitaxel chemotherapy, and a washout period of >=42 days for nitrosoureas and mitomycin). 4. Known active central nervous system metastases and/or carcinomatous meningitis. Treated brain metastasis subjects may participate in the study, provided that their condition is stable and they do not have any of the following conditions: (1) Progressive or new-onset neurological deficits, seizures, evidence of increased intracranial pressure, vomiting, or headache; (2) Evidence of recurrence/progression on MRI at least 4 weeks prior to the first dose of study treatment, and any neurological symptoms have not returned to baseline levels; (3) Evidence of new brain metastases or enlargement of brain metastases, requiring the use of corticosteroids at least 3 days prior to the administration of study drugs. 5. Known history of malignant tumors (excluding subjects who have successfully undergone definitive surgery for cutaneous basal cell carcinoma, superficial bladder cancer, cutaneous squamous cell carcinoma, or cervical carcinoma in situ), unless the subject has received potentially curative treatment and has not experienced disease recurrence within 5 years since the start of treatment. 6. Uncontrolled pleural effusion, pericardial effusion, or recurrent ascites requiring >=1 drainage per month; 7. Tumor invasion into important arteries leading to high-risk bleeding risk, with significant perforation risk or already formed fistulas; 8. Residual toxic reactions (excluding hair loss, fatigue, and Grade 2 hypothyroidism) or clinically significant laboratory test abnormalities above Grade 1 (CTCAE v5.0) due to previous anti-tumor treatment (including biologics, targeted therapy, chemotherapy, or radiotherapy); 9. History of severe cardiac dysfunction, stroke, or transient ischemic attack (TIA) within 6 months prior to enrollment. History of ventricular tachycardia or torsade de pointes arrhythmia. Any clinically significant abnormalities in rhythm, conduction, or morphology of the resting electrocardiogram (ECG), such as QTc > 450 ms in males and QTc > 470 ms in females, presence of complete left bundle branch block or third-degree atrioventricular block. Presence of clinically significant cardiac diseases, including acute myocardial infarction, Grade III or IV congestive heart failure (New York Heart Association classification), unstable angina pectoris, or arrhythmias requiring treatment, occurring within 6 months prior to the first study treatment. Note: Subjects with arrhythmias may be enrolled if they are receiving antiarrhythmic drug therapy and the screening electrocardiogram (ECG) shows a controlled rhythm; 10. Pulmonary embolism or deep vein thrombosis within 3 months prior to the first dose o
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective relief rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival, OS;Disease control rate, DCR;Duration of relief, DOR;Progression free survival, PFS; | — |
Countries
China
Contacts
Public ContactWang Lu
Fudan University Shanghai Cancer Center
Outcome results
None listed