Phase I Study of SC-43 Oral Solution in Subjects With Refractory Solid Tumors

Inclusion Criteria:

1. Either gender, aged 20 to 75 years old (inclusive; the legal age of consent majority is 20 years old in Taiwan)
2. Life expectancy ≥ 12 weeks
3. With histologically or cytologically confirmed solid tumor(s) that is refractory to standard treatments, or for which a standard therapy is not available or is no longer effective
4. With at least one measurable target lesion as measured by MRI or CT according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1 criteria
5. Subject who has received local therapies (such as surgery, radiation therapy, hepatic arterial embolization, or chemoembolization) is eligible. Local therapies must be completed at least 4 weeks prior to the baseline scan. However, the local therapy-treated tumor should be excluded for evaluation.
6. Eastern Cooperative Oncology Group (ECOG) performance status ≦2
7. If female subject or female spouse/partner of male subject is of childbearing potential, she/he must agree to use highly effective contraceptives from signing informed consent to 28 days after the last dose of study drug administration.

   At least two forms of birth control must be adopted and one of which must be a barrier method. Acceptable forms include:
   * Established use of oral, injected or implanted hormonal methods of contraception
   * Placement of an intrauterine device (IUD) or intrauterine system (IUS)
   * Barrier methods of contraception: condom, or occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/suppository
8. Dated and signed informed consent

Exclusion Criteria:

1. With primary central nervous system (CNS) malignancies or clinically active CNS metastases
2. The target solid tumor is lymphoma
3. Any of the following hematologic abnormalities:

   1. Hemoglobin \< 8.0 g/dL
   2. Absolute neutrophil count (ANC) \< 1,000/μL
   3. Platelets \< 80,000 /μL
4. Any of the following serum chemistry abnormalities:

   1. Total bilirubin \> 1.5 × ULN
   2. AST or ALT \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
   3. γ-GT \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
   4. ALP \> 2.5 × ULN (\> 5 × ULN in patients with HCC)
   5. Serum albumin \< 2.5 g/dL
   6. Creatinine \> 1.5 × ULN
   7. aPTT \>1.5 × ULN
   8. INR \>1.5 × ULN
   9. Any other ≥ Grade 3 (according to CTCAE v.5.0) laboratory abnormality at baseline (other than those listed above) Note: ULN = upper limit of normal; AST = aspartate transaminase; ALT = alanine transaminase; γ-GT = Gamma-glutamyl transferase; ALP = alkaline phosphatase; aPTT = activated partial thromboplastin time; INR = international normalized ratio of prothrombin time
5. History of organ or tissue transplantation
6. History of autoimmune disease
7. Active clinically serious infection
8. History of human immunodeficiency virus (HIV) infection
9. Significant cardiovascular disease, including:

   1. History of New York Heart Association (NYHA) class III or IV congestive heart failure
   2. Ongoing uncontrolled hypertension
   3. History of congenital long QT syndrome
   4. Ongoing prolonged corrected QT (QTc) interval defined as ≥ 450 msec
   5. History of serious ventricular arrhythmia (i.e., ventricular tachycardia or ventricular fibrillation)
10. With ascertained hypersensitivity to any ingredient of the investigational product or drugs with similar chemical structures, including sorafenib. If there is suspicion that the subject may have an allergy, the subject should be excluded.
11. Uncontrolled nausea or vomiting or any symptom that would prevent the ability to comply with daily oral SC-43 treatment
12. With significant gastrointestinal disorder(s) within 12 weeks prior to Screening that would, in the opinion of the investigator, prevent absorption of an orally available agent
13. Active bleeding during the last 4 weeks prior to Screening Visit
14. Requirement for ongoing immunosuppressive agents (including azathioprine, mycophenolate, cyclophosphamide, chlorambucil, methotrexate, cyclosporine), or systemic steroid with equivalent dosage higher than prednisolone 30 mg/day for more than 14 days
15. Received an investigational agent within 4 weeks prior to Screening
16. Had previous anti-cancer therapy (surgery, radiotherapy, chemotherapy, targeted therapy, immunotherapy, biology therapy, or hormonal therapy) within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to Screening Visit or has ongoing side effects (≥ Grade 2, according to CTCAE v.5.0) due to previously administered agents
17. Has undergone major surgery within 4 weeks before Screening Visit, or has elective or planned surgery to be conducted during the trial
18. Female with childbearing potential who has positive urine or serum pregnant test at Screening Visit or lactating
19. Is not considered to be suitable for this study, in the opinion of the investigator