Study of ST-1898 in Advanced Renal Cell Carcinoma

1. Age >= 18 years
2. Life expectancy of three months or more
3. Histologically and medical imaging confirmed unresectable, locally advanced or metastatic renal cell carcinoma. In Dose Escalation Phase, subjects should be progressed with standard therapy, not eligible for standard therapy or no standard therapy available；in Dose Expansion Phase, subjects should be progressed with prior immune checkpoint inhibitor and tyrosine kinase inhibitor therapy.
4. With agreement to provide a tumor tissue specimen
5. Has the ability to understand and willingness to sign a written ICF before the performance of any study-specific procedures on this protocol
6. Has at least one measurable lesion as defined by RECIST version 1.1
7. Has an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0-1

8. Has adequate organ function defined as follows:

   1. Bone marrow : absolute neutrophil count(ANC)≥1.5×10\^9 /L, Hb level ≥ 90 g/L and platelet count (PLT) ≥ 90 x10\^9/L, no transfusions and no use of colony stimulating factor within 2 weeks prior to routine blood test) at screening;
   2. Liver: transaminase levels (AST/ALT) ≤ 3.0×upper limit of normal (ULN), AST/ALT ≤ 5×ULN for liver metastasis; total bilirubin (TBILI) ≤ 1.5 ×ULN;
   3. Kidney: Creatinine ≤1.5×ULN
   4. Heart: LVEF≥50%
   5. Coagulation function: INR≤1.5×ULN，APTT≤1.5×ULN (except for the prophylactic use of anticoagulants)
   6. Urine protein ≤1+; or in the condition of urine protein ≥2+, quantitative measurement of the 24-hour urine protein is \< 1g
9. Women of child bearing potential must have a negative serum pregnancy test within 7 days before first study drug administration. Female patients of child bearing potential, or a male patients with a female partner of child-bearing potential (defined as all women physiologically capable of becoming pregnant), must agree to use a highly effective method of contraception during screening, during the period of drug administration and for 120 days after stopping study drug administration.

Exclusion Criteria:

1. Has received another anti-tumor therapy within two weeks or within 5 half-life of anti- tumor drug prior to the first dose
2. Has had major surgery within 4 weeks before the first study drug administration (except tumor biopsy, puncture, invasive dental procedures such as tooth extraction, dental implants etc.)
3. Current or previous severe retinopathy who, in the judgment of the Investigator or specialist, are not suitable for enrollment

4. Has had any history of major cardiovascular event within 6 months prior to study drug administration including but not limited to :

   1. Serious arrhythmia or cardiac conduct abnormality , such as degree II-III atrioventricular block or ventricular arrhythmia needs to be treated
   2. QTc interval extension: male >450 ms, female >470 ms
   3. Acute coronary syndrome, stroke, deep vein thrombosis, pulmonary- thromboembolism, arterial thrombosis, congestive heart failure, aortic dissection etc.
   4. New York Heart Association Class ≥ II
   5. Has uncontrolled hypertension, as defined by a sustained blood pressure (BP) > 140/90 mmHg with antihypertensive treatment
5. Has brain metastases with symptoms or with evidence of progression
6. Has Interstitial lung disease or radiation pneumonia requiring treatment by steroid
7. Has other malignant tumors in the last 5 years (not including non-melanoma skin cancer, breast cancer or cervical cancer in situ, and Non-Muscle-invasive bladder cancer that have been cured)
8. Has ≥ grade 3 hemorrhage/bleeding event within 6 months prior to study drug administration or currently ≥ grade 2 hemorrhage or event of high risk of hemorrhage) including active gastrointestinal ulcer or esophageal varices
9. Concomitant medication with strong inducers of CYP3A4, strong inhibitors of CYP3A4, or CYP3A4 substrates with narrow therapeutic windows within 2 weeks prior to first dose.
10. Has not recovered from toxicities caused by prior therapy to CTCAE≤ Grade 1 (except for peripheral neuropathy becoming ≤Grade 2, alopecia, and other events judged tolerable by the Investigator and without safety risks).
11. Active hepatitis B (asymptomatic hepatitis B carriers with HBV DNA \< 2000 IU/mL are allowed to be enrolled), hepatitis C virus (HCV) antibody-positive and HCV-RNA- positive, or other active hepatitis, clinically significant moderate-to-severe cirrhosis, are allowed to receive prophylactic antiviral therapy other than interferon.
12. Has acute bacterial, viral or fungal infections, requiring systemic anti-infective treatment.
13. HIV positive
14. Pregnant or lactating females
15. Drug or alcohol dependents
16. Has significant disorder of neurology or mental disease or poorly compliance
17. Unable to swallow oral medications or condition or conditions that in the judgment of the Investigator which severely interfere with gastrointestinal absorption, such as dysphagia, intestinal obstruction, etc.
18. Clinically uncontrollable third interstitial effusion that, in the judgment of the Investigator, is unsuitable for enrollment.
19. Has a history of other serious systemic disease, or any other reason that might interfere with participation in trial or interfere with interpretation of trial results, in the judgement of the Investigator, that are not qualified to participate in this trial.