A Comparative Study of Pharmacokinetics, Safety, and Immunogenicity of RPH-030 and Vectibix® in Patients With Metastatic Colorectal Cancer With Wild-type RAS as First-line Therapy in Combination With FOLFIRI

Exclusion Criteria43

• Prior systemic antitumor therapy (except for neoadjuvant or adjuvant fluoropyrimidine-based chemotherapy)
• Prior therapy with anti-EGFR monoclonal antibodies (e.g., cetuximab, panitumumab) or small molecule EGFR tyrosine kinase inhibitors (e.g., gefitinib, erlotinib, afatinib)
• Concomitant systemic immunotherapy or hormonal cancer therapy, or concurrent use of other cancer treatments not specified in the Protocol
• Major surgery within 28 days, or radiotherapy (except for palliative radiotherapy) with residual signs of radiation toxicity within 14 days prior to the planned date of randomization
• Presence of BRAF gene mutation (if BRAF testing results are unavailable, testing will be performed at a central laboratory; results must be obtained and evaluated prior to randomization)
• Severe comorbidities or life-threatening acute complications of the underlying disease (including massive pleural, pericardial, or peritoneal effusion requiring intervention)
• Paralytic ileus, gastrointestinal obstruction, or uncontrolled diarrhea (disabling symptoms despite adequate treatment)
• Central nervous system (CNS) metastases that are progressive, symptomatic (e.g., cerebral edema, spinal cord compression), or requiring glucocorticosteroids at doses >10 mg/day (prednisolone equivalent), >1.5 mg/day (dexamethasone equivalent), or anticonvulsants, whereas patients with treated and stable brain metastases (for ≥4 weeks), asymptomatic non-progressive lesions not requiring steroids/anticonvulsants for ≥4 weeks, or newly diagnosed asymptomatic lesions requiring no therapy may be included
• Ongoing comorbidities at the time of screening that increase the risk of adverse events during study therapy, including:
• Stable angina pectoris (Canadian Cardiovascular Society Grade III-IV), unstable angina, or a history of myocardial infarction within 1 month prior to the planned date of randomization
• Clinically significant cardiac arrhythmias (patients with controlled heart rate/rhythm are eligible)
• Chronic heart failure (New York Heart Association \[NYHA\] Class III-IV)
• Uncontrolled hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg despite antihypertensive therapy)
• Severe respiratory failure
• Current severe uncontrolled systemic disease
• Any other medical condition or comorbidity that, in the investigator's opinion, significantly increases the risk of adverse events during the study
• Gilbert's syndrome at randomization or in medical history
• Hematologic abnormalities:
• Absolute neutrophil count (ANC) <1.5 × 10\^9/L
• Platelet count <100 × 10\^9/L
• Hemoglobin <90 g/L
• Renal impairment:
• \- Serum creatinine >1.5 × ULN or Glomerular Filtration Rate (GFR) <45 mL/min (calculated via CKD-EPI formula)
• Hepatic impairment:
• Total bilirubin ≥ 1.5 × ULN
• AST or ALT ≥ 3.0 ULN (≥ 5 × ULN for patients with liver metastases)
• Alkaline phosphatase (ALP) ≥ 5 × ULN
• Feasibility of radical resection of all metastatic lesions
• History of other malignancies that are progressive or required treatment within 5 years prior to signing the ICF, excluding radically treated cervical carcinoma in situ, breast cancer in situ, or basal/squamous cell skin carcinoma
• Conditions limiting the patient's ability to comply with protocol requirements (e.g., dementia, neurological or psychiatric disorders, drug addiction (excluding the use of narcotic analgesics for pain management), alcohol dependence, etc.). Religious or personal beliefs that may potentially limit standard therapies within the study (e.g., refusal of blood transfusions) are considered conditions limiting protocol compliance
• Concurrent participation in other interventional clinical trials, participation in other clinical trials within 30 days prior to signing the ICF (provided the patient received at least one dose of investigational therapy), or prior participation in this clinical trial (provided the patient received at least one dose of panitumumab)
• Acute infectious diseases or exacerbation of chronic infections within 28 days prior to the planned date of randomization
• Major surgery within 28 days prior to the planned date of randomization. Major surgery is defined as procedures involving entry into a major body cavity (abdomen, chest, or skull) performed under general anesthesia. Placement of a venous port system for antitumor therapy or an intestinal stoma is not considered major surgery
• Positive test result for any of the following: hepatitis B surface antigen (HBsAg), antibodies to hepatitis C virus (anti-HCV), antibodies to human immunodeficiency virus types 1 and 2 (anti-HIV-1 and anti-HIV-2), or a blood test for syphilis at screening or within 3 months prior to the planned date of randomization
• Inability to receive intravenous (IV) administration of the investigational product
• Contraindication to any type of intravenous contrast enhancement (non-contrast chest CT is permitted if medically indicated)
• Current continuous daily treatment with corticosteroids at doses >10 mg/day (prednisolone equivalent) or >1.5 mg/day (dexamethasone equivalent), excluding topical steroids
• Hypersensitivity to any components of the study drugs specified in the protocol or intolerance to any premedication drugs
• History of hypersensitivity to monoclonal antibody (mAb) therapies
• Pregnancy or breastfeeding
• Consumption of more than 10 units of alcohol per week or a history of alcoholism or drug addiction. One unit of alcohol is defined as 250 mL of beer, 125 mL of wine, or 30 mL of spirits
• Presence of any other significant comorbidities or conditions that, in the reasonable opinion of the Investigator, may adversely affect the patient's participation and well-being in the study and/or confound the evaluation of study results
• Inability to perform venous blood sampling or to insert a venous catheter required for biosample collection (applicable to patients enrolled in the pharmacokinetic study)