Becotatug Vedotin Combined With Cetuximab in the Later-line Treatment of Metastatic RAS Wild-type Colorectal Cancer

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 of study drug
• •11\. Uncontrolled or poorly controlled hypertension (e.g., systolic blood pressure \>160 mmHg or diastolic blood pressure \>100 mmHg) or hyperglycemia
• •12\. Active acute or chronic inflammatory skin diseases, previous history of Steven-Johnson syndrome, toxic epidermal necrolysis
• •13\. Known hypersensitivity to any component or excipient of Vibecotar (citric acid monohydrate, sodium citrate dihydrate, trehalose dihydrate, sodium chloride, and polysorbate 80), or known hypersensitivity to other previous anti-EGFR drugs (including the investigational study drug) or other monoclonal antibodies with a grade ≥3 reaction
• •14\. Known active hepatitis B or C. Active hepatitis B is defined as known HBsAg positivity and HBV DNA ≥500 IU/mL. Active hepatitis C is defined as known hepatitis C antibody positivity and known quantitative hepatitis C virus (HCV) RNA result greater than the lower limit of detection. Presence of other severe liver diseases, including chronic autoimmune liver disease, primary biliary cirrhosis or sclerosing cholangitis, alcoholic liver disease, or non-alcoholic steatohepatitis (NASH)
• •15\. Concurrent severe, uncontrolled infection or known human immunodeficiency virus (HIV) infection, or diagnosis of acquired immune deficiency syndrome (AIDS) or uncontrolled autoimmune disease
• •16\. Subjects with active bacterial, viral, fungal, rickettsial, or parasitic infections requiring intravenous anti-infective therapy (unless treated and resolved prior to study drug administration)
• •17\. Subjects with moderate to severe dyspnea at rest due to advanced cancer or its complications, or severe primary lung disease (currently requiring continuous oxygen therapy and with oxygen saturation \<93% without supplemental oxygen), or any history of interstitial lung disease (ILD) (including ILD requiring oral or intravenous corticosteroids) or non-infectious pneumonia
• •18\. Subjects undergoing immunology-based therapy for any reason, including long-term systemic steroid use equivalent to \>10 mg/day of prednisone within 7 days prior to the first dose of study drug or at any time during the study participation. Note: Inhaled or topical steroids equivalent to ≤10 mg/day of prednisone, or short-term use of corticosteroids equivalent to \>10 mg/day of prednisone (e.g., as prophylaxis before contrast media administration) is permitted
• •19\. Subjects with chronic autoimmune or inflammatory diseases requiring systemic treatment or undergoing systemic treatment within the past 2 years, including but not limited to inflammatory bowel disease, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (exceptions: vitiligo, hypothyroidism undergoing stable hormone replacement therapy, controlled asthma, type I diabetes, Graves' disease, and Hashimoto's thyroiditis)
• •20\. Subjects who test positive for pregnancy or are breastfeeding. Female and male subjects who do not plan to use adequate contraception during the treatment period and within 180 days after the last dose of study treatment any other diseases or clinically significant laboratory parameter abnormalities, severe medical or psychiatric conditions/conditions, and substance abuse including alcohol abuse, that the investigator believes may compromise subject safety, study integrity, affect subject participation in the study, or interfere with study objectives and outcome analysis.