Overview
This is a Phase Ⅱ/Ⅲ study. The purpose of this study is to evaluate the efficacy and safety of RC148 combined with chemotherapy for the first-line treatment of unresectable metastatic colorectal cancer (CRC)
Description
Primary objective in Phase II: To preliminarily evaluate the efficacy of RC148 combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.
Primary objective in Phase III: To evaluate the efficacy of RC148 combined with chemotherapy compared with bevacizumab combined with chemotherapy as first - line treatment for unresectable or metastatic CRC.
Eligibility
Inclusion Criteria:
- Voluntarily agree to participate in the study, sign the informed consent form, and be able to comply with the study protocol.
- Aged 18-75 years old (including 18 years old and 75 years old).
- Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
- Expected survival period ≥ 12 weeks.
- At least one measurable lesion according to RECIST v1.1 criteria.
- Histologically or cytologically confirmed colorectal adenocarcinoma, judged by the investigator as unsuitable for curative treatment, and no prior systemic anti-tumor treatment in the recurrent or metastatic stage.
- Subjects must be able to provide tumor tissue samples for biomarker detection.
- Adequate bone marrow, liver, kidney, and coagulation function.
- Female subjects of childbearing potential must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment, and must have a negative blood pregnancy test within 7 days before study enrollment; male subjects must agree to use at least one medically approved contraceptive method during the study treatment and for 6 months after the end of the study treatment.
Exclusion Criteria:
- Known to have microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR).
- Imaging shows obvious tumor necrosis or cavitation, and the investigator judges that participation in the study may increase the risk of bleeding.
- Subjects with brain metastases.
- Toxicities from prior anti-tumor therapy have not recovered to ≤ grade 1 according to NCI-CTCAE v6.0.
- Known hypersensitivity or delayed-type allergy to any component of the study drug or similar drugs.
- Subjects with refractory nausea and vomiting, chronic gastrointestinal diseases, or other diseases that may interfere the adequate absorption, distribution, metabolism, or excretion of oral drugs.
- Subjects with acute, chronic, or symptomatic infections.
- Subjects with diagnosed or suspected interstitial lung disease (ILD), drug-related pneumonia, radiation pneumonitis, severe impairment of lung function, or other lung diseases.
- Subjects with active inflammatory bowel disease, a history of gastrointestinal perforation and/or fistula, or clinical symptoms of gastrointestinal obstruction.
- Subjects with severe arterial/venous thromboembolic events within 6 months before randomization.
- Active gastrointestinal bleeding, hemoptysis, peptic ulcer, or hemorrhagic events requiring intervention within 28 days before randomization; or presence of severe esophagogastric varices or epistaxis.
- Presence of symptomatic or intervention-requiring third-space effusions.
- Subjects with active or previously diagnosed autoimmune diseases that may recur.
- History of other invasive malignant tumors within 5 years before randomization, or presence of any residual evidence of previously diagnosed malignant tumors.
- Subjects who are pregnant, lactating, or planning to become pregnant.
