A Study of HS-10516 in Patients With Advanced Clear Cell Renal Cell Carcinoma

A Phase Ia/Ib Study of HS-10516 to Investigate the Safety, Tolerance, Pharmacokinetic and Efficacy in Patients With Advanced Clear Cell Renal Cell Carcinoma

The aim of the Phase Ia portion is to identify the maximum tolerated dose or maximum acceptable dose MTD/MAD of HS-10516. The phase Ib portion will evaluate the preliminary efficacy of HS-10516 in ccRCC.

This is a Phase Ia/Ib open label multicenter study of HS-10516 in Chinese patients aged 18 years or older with advanced clear cell renal cell carcinoma who have failed or are unavailable/intolerant to standard of care. HS-10516 as a single agent, is administrated orally once daily. The aim of phase Ia, a dose escalation study, is to identify the MTD/MAD of HS-10516. The goal of Phase Ib, a dose expansion study, is to evaluate the safety, pharmacokinetics and antitumor efficacy of HS-10516.

Inclusion Criteria:

1. Male or female from 18 to 75 year-old
2. Histologically confirmed locally advanced or metastasis clear cell renal cell carcinoma whose standard treatment failed or proven unavailable or intolerant
3. Has at least one non-CNS target lesion per RESIST v1.1
4. Has an Eastern Cooperative Oncology Group performance status of 0-1
5. Has a life expectancy of ≥ 12 weeks
6. Should use adequate contraceptive measures throughout the study
7. Females subject must not be pregnant at screening
8. Has the ability to understand and willingness to sign a written informed consent before the performance of the study

Exclusion Criteria:

1. Received or being received treatment as follows:

   1. Hypoxia-induced factor inhibitors
   2. Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
   3. Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment
   4. Colony-stimulating factors (CSFs) within 4 weeks before the first dose of study treatment
   5. Local radiotherapy within 2 weeks prior to the first dose of study treatment; more than 30% of bone marrow radiotherapy or large-area irradiation within 4 weeks before the first dose of study treatment.
   6. Major surgery within 4 weeks prior to the first dose of study treatment.

2. Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen

3. Has failed to recover from a ≥ grade 2 adverse event due to prior anti-tumor therapy

4. Has another malignancy or a history of another malignancy

5. Has inadequate bone marrow reserve or organ dysfunction

6. Has a clinically significant bleeding events or tendency within 1 month prior to the first dose of study treatment

7. Has severe infections within 4 weeks prior to the first dose of study treatment

8. Has digestive system diseases may influencing ADME of study drug

9. Has a history of severe hypersensitivity reaction, or proven allergic to HS-10516 or its metabolics

10. Has any disease or condition would compromise subject safety or interfere with study assessments by investigator's decision