Overview

The primary goal of Phase Ib Study is to evaluate the safety of Suvemcitug in combination with trifluridine/tipiracil tablets in colorectal cancer participants.

The primary goal of Phase III Study is to evaluate the efficacy of Suvemcitug in combination with trifluridine/tipiracil tablets in colorectal cancer participants. Researchers will compare Suvemcitug + trifluridine/tipiracil tablets with placebo (a look-alike substance that contains no drug)+ trifluridine/tipiracil tablets to see if Suvemcitug + trifluridine/tipiracil tablets works better in treating refractory metastatic colorectal cancer.

Eligibility

Inclusion Criteria:

• 1\. Confirmed by histological and/or cytological examination as unresectable metastatic colon or rectal adenocarcinoma;
• 2\. At least one measurable tumor lesion (RECIST v1.1);
• 3\. Previously received fluorouracil, oxaliplatin, and irinotecan based chemotherapy; had previously undergone or was unsuitable for anti-VEGF therapy. (For participants with RAS wild-type, had previously undergone or was unsuitable for anti-EGFR therapy.);
• 4\. Refractory metastatic colorectal cancer having progressed on or are intolerant to the last systemic treatment;
• 5\. Good organ and bone marrow function (no administration of hematopoietic growth factors, blood transfusion, or platelets within 14 days before screening hematology test);
• 6\. RAS mutation status confirmed by testing tumor tissue and /or blood sample.

Exclusion Criteria:

• 1\. Having a second active primary malignancy within the past 5 years;
• 2\. Symptomatic central nervous system (CNS) metastases or CNS metastases requiring local CNS-directed therapy (e.g., radiotherapy or surgery) or corticosteroid treatment within 2 weeks prior to the first administration of the study treatment;
• 3\. Any active infection requiring systemic treatment within 2 weeks prior to the initiation of the study treatment;
• 4\. Pleural effusion, pericardial effusion, or ascites that is uncontrolled or has required drainage or medical intervention within 4 weeks prior to the first administration of the study treatment;
• 5\. Received systemic immuno suppressive therapy within 4 weeks prior to randomization (excluding prophylactic use or chronic low-dose steroids \[≤20 mg/day prednisone equivalent dose\]);
• 6\. Currently taking or has recently taken (within 10 days prior to the first dose) aspirin (\>325 mg/day);
• 7\. Active or chronic hepatitis B (HBsAg or HBcAb positive and HBV DNA≥2000 IU/mL or ≥10000 copies/mL) or hepatitis C infection (HCV antibody positive and HCV RNA≥ULN);
• 8\. Clinically significant cardiovascular disease within 6 months prior to the first administration of the study treatment;symptomatic coronary artery disease requiring medication; arrhythmia requiring medication (excluding asymptomatic atrial fibrillation with controlled ventricular rate); QTcF interval \>470 ms at rest state; or uncontrolled hypertension or pulmonary hypertension;
• 9\. Known hereditary or acquired bleeding and thrombotic tendencies (e.g., hemophilia, coagulation disorders, thrombocytopenia, hypersplenism, etc.); clinically significant bleeding events, arterial or deep venous thrombotic events, or superficial venous thrombosis and intermuscular venous thrombosis requiring intervention within 6 months prior to enrollment;
• 10\. Participants with proteinuria (urine protein \>2+ found during screening examinations; or urine protein 2+ with 24-hour urine protein quantification ≥1g/24h);
• 11\. Participants with a history of intestinal obstruction (including incomplete intestinal obstruction) within 1 month prior to enrollment; participants with a history of abdominal fistula, gastrointestinal perforation, or abdominal abscess.