A Study of ST-1898 for Unresectable or Metastatic Melanoma

Inclusion criteria

• Age >= 18 years
• Life expectancy of three months or more
• Histologically or cytologically confirmed unresectable or metastatic stage III or IV acral melanoma that was progressed with conventional therapy
• Recommendation of subject offering archived tissue sample or previous biomarker test report. If archived tumor sample is not available, a fresh biopsy is optional, which need to be taken from needle biopsy or core needle biopsy (fine needle biopsy not allowed)
• Eastern Cooperative Oncology Group performance status (PS) ≤ 1
• At least one measurable lesion per RECIST 1.1
• Has adequate organ function defined as follows:

• Absolute neutrophil count ≥ 1.5 ×10^9/L, Platelets ≥ 75× 10^9/L and Hemoglobin ≥ 90 g/L (no blood transfusions, no platelet transfusions and no use of colony stimulating factor within 2 weeks prior to routine blood test) at screening;
• Serum creatinine ≤1.5 × upper limit of normal (ULN)
• Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤ 2.5 ULN, AST/ALT ≤ 5 ULN for liver metastasis;
• Total bilirubin ≤ 1.5 ULN
• International normalized ratio (INR) ≤ 1.5 ULN, or prothrombin time (PT) ≤1.5 ULN
• Activated partial thromboplastin time (APTT) ≤1.5 ULN
• Serum albumin ≥30 g/L
• Willing and able to provide written Informed consent.
• Eligible male and female subjects with fertility activity or their sexual partners must use effective contraception during study period and though 90 days after last study treatment. Women of child-bearing age must have a negative serum pregnancy test within 7 days before first study treatment

Exclusion criteria

• Subjects with one of the following conditions prior to first dose, including, but not limiting to：

• A history of antitumor therapy within 4 weeks, including chemotherapy, radiotherapy, biotherapy, endocrine therapy or immunotherapy, etc.;
• A history of oral fluoropyrimidines and small molecular targeted-drug therapy within 2 weeks or 5 half-life time （the longer time taken as final）;
• A history of traditional Chinese medicine with antitumor indication within 2 weeks;
• A history of being participant in clinical trial of other unapproved drugs within 4 weeks;
• A major operation or severe trauma within 4 weeks, （except tumor biopsy, puncture,）invasive dental procedures such as dental extraction, dental implants etc.
• Current or previous severe retinopathy who, in the judgment of the Investigator, are not suitable for enrollment
• A history of clinically significant cardiovascular or cerebrovascular disease, including, but not limiting to:

• Severe arrhythmia or heart conduction disturbance, such as second-degree or third-degree atrio-ventricular block or ventricular arrhythmia indicated with medical intervention
• QTc (by Fridericia): male >450 ms, female >470 ms
• Major cardiovascular events within 6 months prior to first dose, including acute coronary syndrome, stroke, deep vein thrombosis, pulmonary-thromboembolism and other ≥Grade 3 arterial-thrombosis events, or congestive heart failure, or aortic dissection etc.；
• New York Heart Association Class ≥ II；
• Left ventricular ejection fraction（LVEF）<50%；
• Uncontrolled hypertension (blood pressure≥140/90 mmHg even with antihypertensive therapy)
• Subjects with active leptomeningeal disease or brain metastases without being well controlled, except subjects with asymptomatic or treated brain metastases being stable imaging between 12 weeks before screening；
• Subjects with interstitial lung disease or radiation pneumonia in needs of corticosteroids therapy
• Subjects with clinically uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage or medical intervention within 7 days prior to first dose;
• Subjects with malignant tumors in the last 5 years (not including non-melanoma skin cancer, breast cancer or cervical cancer in situ, and superficial bladder transient cell carcinoma that have been cured)
• A history of ≥ grade 3 bleeding episodes within 6 months prior to first dose; or currently ≥ grade 2 hemorrhage, with angioneoplasm/ vascular malformation, with high bleeding risks (such as active peptic ulcer or esophageal varices)
• Within 2 weeks prior to first dose of concomitant medication with strong inducers of CYP3A4, strong inhibitors of CYP3A4, or substrates with narrow therapeutic windows of CYP3A4;
• Subjects with ≥ Grade 2 (by CTCAE) toxicities caused by previous therapy (not including ≤Grade 2 peripheral neuropathy, alopecia, or other tolerated and no possible safety hazard events as determined by the investigator);
• Subjects with active hepatitis B, unless HBV-DNA titer in the normal range (for subjects with positive HBsAg but HBV-DNA titer eligible, prophylactic antiviral therapy except interferon is allowed); active hepatitis C (ANTI-HCV positive)；
• Subjects with positive HIV antibodies or Treponema pallidum antibodies;
• Subjects with acute bacterial, viral or fungal infections, and in needs of systemic antimicrobial therapy;
• Pregnant or lactating females;
• Subjects with significant neuropsychiatric disorders, leading to poor compliance;
• Subjects with underlying diseases (including abnormal laboratory investigations), alcohol, drug abuse, or drug dependence, all which affect the interpretation of toxicities or adverse event, or decrease;
• Subjects with oral administration impossible, or in the conditions of malabsorption as determined by the investigator, such as dysphagia and intestinal obstruction, etc.;
• Subjects with significant liver cirrhosis, hepatatrophy, portal hypertension, or more than moderate volume of ascites;
• A history of organ transplant;
• A history of other severe systemic disease, or not suitable as determined by the investigator due to any other reasons;
• A history of inoculation with live vaccine within 28 days prior to first dose. Note: Seasonal influenza vaccine is a broadly inactivated vaccine and is permitted. Inactivated COVID-19 vaccines are permitted. COVID-19 mRNA vaccines are not allowed. Intranasal influenza vaccines are live vaccines and are not allowed.