A Study of SC-0191 in Subjects With Metastatic Colorectal Cancer

Inclusion Criteria:

1. Subjects voluntarily participate in the clinical study and sign an informed consentform;
2. Male or female subjects aged ≥18 years;
3. Subjects diagnosed with stage IV colorectal cancer confirmed by histology or cytologyand not suitable for curative surgical treatment;
4. Subjects who have previously received fluoropyrimidine-based chemotherapy,oxaliplatin, and irinotecan with or without anti-EGFR or anti-VEGF targeted therapy,and experienced disease progression or intolerance to the most recent treatmentregimen; the number of prior lines of systemic antitumor therapy for advancedcolorectal cancer does not exceed 2 lines;
5. ECOG performance status of 0 to 1;
6. Expected survival of ≥3 months;
7. At least one measurable lesion according to RECIST 1.1 criteria, defined as a lesionwith a longest diameter ≥10 mm on CT scan or MRI (excluding lymph nodes) or a shortdiameter ≥15 mm for lymph nodes. Lesions located in previously irradiated or otherwiselocally treated areas are generally not considered measurable unless there isdocumented disease progression;
8. Adequate organ function and bone marrow hematopoietic function;
9. Fertile subjects (both male and female) must agree to use a reliable method ofcontraception (hormonal or barrier method, or abstinence) with their partners for atleast 6 months from the time of signing the informed consent form until the last doseof the study drug; female subjects of childbearing potential must have a negativepregnancy test within 14 days before the first use of the investigational drug.

Exclusion Criteria:

1. Subjects known to be MSI-H who have not received immunotherapy;
2. Subjects with spinal cord compression, symptomatic/unstable brain metastases, orleptomeningeal metastases. Exclusion: Subjects with stable symptoms of brainmetastases after prior treatment (completion of definitive radiotherapy and/orsurgery, cessation of corticosteroid therapy, and stable symptoms for at least 14days);
3. Subjects with radiological evidence of tumor invasion or encasement of major vessels (Cohort A);
4. Subjects with uncontrollable pleural effusion, ascites, or pericardial effusion atscreening;
5. Subjects with a history of other malignant tumors within 5 years prior to study druginitiation, except for early-stage tumors cured by curative treatment, such as basalcell carcinoma or squamous cell carcinoma of the skin, cervical carcinoma in situ,ductal carcinoma in situ of the breast, superficial bladder cancer, localized prostatecancer, etc.;
6. Subjects with significant cardiovascular diseases, including NYHA class II-IV heartfailure, congestive heart failure, second-degree or higher atrioventricular block,myocardial infarction within the past 6 months, unstable arrhythmias or angina,significant QT interval prolongation (baseline-corrected QTc interval >470milliseconds on ECG), stroke within the past 6 months, or PTCA (percutaneoustransluminal coronary angioplasty) or CABG (coronary artery bypass grafting) withinthe past 6 months;
7. Subjects with poorly controlled hypertension;
8. Subjects with viral infectious diseases at screening meeting the following criteria:
9. HIV seropositivity;
10. Hepatitis B: HBsAg positivity with HBV-DNA quantification above the upper limit ofnormal;
11. Hepatitis C: HCV antibody positivity with HCV-RNA quantification above the upper limitof normal;
12. Subjects with active infections requiring systemic antimicrobial therapy as judged bythe investigator, deemed unsuitable for participation in this study;
13. Subjects who have undergone allogeneic tissue/organ transplantation;
14. Subjects with malabsorption syndrome or other gastrointestinal abnormalities that maysignificantly affect oral drug absorption (such as ulcerative lesions, uncontrollablenausea, vomiting, diarrhea, malabsorption syndrome, and small bowel resection, etc.);
15. Subjects with hereditary bleeding or coagulation disorders, or a history of severenon-traumatic bleeding, or a history of ineffective platelet transfusion (within thepast 1 year before initial study drug administration), or any disease thatsignificantly increases the risk of bleeding;
16. Subjects with a history of any of the following during treatment withBevacizumab-based regimens (or biosimilars): venous or arterial thromboembolic events,gastrointestinal perforation, grade 4 hypertension, grade 3 proteinuria, or grade 3 orhigher bleeding events (Cohort A).
17. Subjects who have undergone major surgery, open biopsy, or experienced severetraumatic injury within 28 days before first use of the investigational drug, or areexpected to undergo major surgery during the study. Subjects who have undergone minorsurgery within 7 days before first use of the investigational drug, such as fineneedle aspiration or core biopsy. Subjects with a history of esophageal varices orbleeding peptic ulcer within 3 months before first use of the investigational drug (Cohort A).
18. Known history of dihydropyrimidine dehydrogenase (DPD) deficiency. History ofdiscontinuing fluoropyrimidine treatment due to ≥3 grade diarrhea (Cohort B).
19. Subjects with a history of interstitial lung disease, drug-induced interstitial lungdisease, radiation pneumonitis requiring corticosteroid treatment, or any clinicalevidence suggesting active interstitial lung disease;
20. Subjects diagnosed with autoimmune diseases during screening or receiving long-termsystemic corticosteroid therapy (dose exceeding 10 mg/day of prednisone or equivalent)or any other form of immunosuppressive therapy due to autoimmune diseases;
21. Subjects whose toxicity from prior anticancer therapy has not resolved to ≤ grade 1 (CTCAE 5.0) (excluding alopecia, decreased hearing, and stable endocrine disorderstreated with alternative therapies);
22. Subjects previously treated with WEE1 inhibitors;
23. Subjects with a history of hypersensitivity reactions to SC0191, Bevacizumab (CohortA), fluoropyrimidines (Cohort B), calcium folinate (Cohort B) active ingredients, ortheir inactive excipients or similar drugs;
24. Subjects who received radiation therapy to more than 25% of the bone marrow areawithin 28 days before first use of the investigational drug;
25. Subjects vaccinated with live vaccines within 28 days before first use of theinvestigational drug.
26. Subjects who received chemotherapy, biologic therapy, endocrine therapy, or otherantitumor therapy within 28 days before first use of the investigational drug; orreceived small molecule targeted therapy within 28 days or 5 half-lives (whichever isshorter) before first use of the investigational drug; or received traditional Chinesemedicine for antitumor therapy within 7 days before first use of the investigationaldrug;
27. Subjects who received systemic corticosteroids (prednisone equivalent >10 mg/day) orother immunosuppressive therapy within 14 days before first use of the investigationaldrug, except for local, ocular, intra-articular, intranasal, and inhalationalcorticosteroid therapy; or received corticosteroids for prophylactic treatment (e.g.,prevention of contrast agent allergy) ;
28. Subjects who received moderate or potent inhibitors of CYP3A4 (such as amprenavir,atazanavir, boceprevir, clarithromycin, conivaptan, darunavir, diltiazem,erythromycin, foscarnet, indinavir, itraconazole, ketoconazole, lopinavir, mibefradil,miconazole, nefazodone, nelfinavir, posaconazole, ritonavir, telithromycin, verapamil,voriconazole, etc.) or moderate or potent inducers of CYP3A4 (such as carbamazepine,felbamate, nevirapine, phenobarbital, phenytoin, primidone, rifampin, efavirenz,modafinil, etc.) within 14 days before first use of the investigational drug;
29. Subjects who require regular use of proton pump inhibitors (PPIs) during the study orreceived PPI therapy within 14 days before first use of the investigational drug (suchas omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole, etc.);
30. Subjects who require long-term therapeutic doses of anticoagulants or antiplateletdrugs (prophylactic use of low-dose anticoagulants is allowed, provided that theanticoagulation parameters specified in the inclusion criteria are met); low-doseanticoagulants may be used to maintain venous catheter patency;
31. Subjects with psychiatric disorders or poor compliance;
32. Pregnant or lactating female subjects;
33. Subjects whom the investigator considers to have other serious systemic medicalhistory, or for other reasons are not suitable for participation in this clinicalstudy.