A Phase II/III Study of HR070803 in Combination With Oxaliplatin, 5-fluorouracil, Calcium Folinate and Bevacizumab Versus FOLFOX in Combination With Bevacizumab for First-line Treatment of Advanced Colorectal Cancer

Prior treatment

• Previous oxaliplatin-containing chemotherapy within 12 months prior to enrolment.
• Previous treatment with irinotecan, immune checkpoint inhibitor, anti-epidermal growth factor receptor or any anti-angiogenic drug.
• Patients with large amount of pleural effusion, ascites or pericardial effusion that could not reach a stable state within 2 weeks prior to enrolment.
• Intestinal obstruction within the 6 months prior to enrolment.
• Gastrointestinal perforation, gastrointestinal fistula, intraperitoneal abscess, and non-gastrointestinal fistula (e.g. tracheoesophageal fistula) within 6 months prior to enrolment.
• Patients with CTCAE≥ grade 3 gastrointestinal bleeding within 6 months prior to enrolment, or any grade gastrointestinal bleeding within 1 month prior to enrolment.
• Patients with CTCAE≥ grade 3 extra-gastrointestinal bleeding within 6 months prior to enrolment, or CTCAE≥ grade 2 extra-gastrointestinal bleeding within 3 months prior to enrolment.

Other illness

• With diagnosed interstitial lung disease.
• Severe cardiovascular and cerebrovascular diseases.
• Uncontrolled hypertension (systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg under regular antihypertensive therapy), and a history of hypertensive crisis or hypertensive encephalopathy.

Lab values

• History of hypersensitivity or contraindications to any of irinotecan liposomes/simulator, irinotecan, other liposomal products, 5-FU, calcium folinate, oxaliplatin, bevacizumab.

Other

• With confirmed MMR deficient (dMMR) or microsatellite instability high (MSI-H).
• With central nervous system metastases.
• Severe gastrointestinal dysfunction (inflammation or diarrhea \> grade 1).
• Peripheral neuropathy \> grade 1.

• Male or female who is 18-75 years of age;
• Histologically-confirmed metastatic and unresectable (Stage IV as defined by American Joint Committee on Cancer \[AJCC eighth edition\]) colorectal adenocarcinoma
• No previous systemic antitumor therapy (including but not limited to systemic chemotherapy, molecularly targeted therapy, immunotherapy, biotherapy, and other investigational therapeutic agents) for colorectal cancer (patients with confirmed relapse ≥6 months after the last administration of neoadjuvant or adjuvant therapy can be enrolled);
• Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 ;
• Life expectancy of ≥ 6 months;
• Vital organ functions meet the criteria.