A Study of HS-10516 in Patients With VHL Syndrome Associated Tumors

This is a Phase Ia/Ib open label multicenter study of HS-10516 in Chinese patients aged 18 years or older with VHL Syndrome Associated Tumors. 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

• Male or female from 18 to 80 year-old
• Patients with advanced clear cellrenal cell carcinoma or von Hippel-Lindau Syndrome associated tumors
• Has an Eastern Cooperative Oncology Group performance status of 0-1
• Has a life expectancy of ≥ 12 weeks
• Should use adequate contraceptive measures throughout the study
• Females subject must not be pregnant at screening
• Has the ability to understand and willingness to sign a written informed consent before the performance of the study.

Exclusion criteria

• Recieved or being received treatment as follows:

• Hypoxia-induced factor inhibitors
• Traditional Chinese medicine indicated for tumors within 2 weeks prior to the first dose of study treatment.
• Cytotoxic chemotherapeutic drugs, investigational drugs or other systematic anti-tumor therapies within 3 weeks before the first dose of study treatment
• Colony-stimulating factors (CSFs) within 4 weeks before the first dose of study treatment
• 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.
• Major surgery within 4 weeks prior to the first dose of study treatment.
• Has a pulse oximetry reading less than 92% at screening, requires intermittent supplemental oxygen, or requires chronic supplemental oxygen
• Has failed to recover from a ≥ grade 2 adverse event due to prior anti-tumor therapy
• Has another malignancy or a history of another non-VHL syndrome associated malignancy
• Has inadequate bone marrow reserve or organ dysfunction
• Has a clinically significant bleeding events or tendency within 1 month prior to the first dose of study treatment
• Has severe infections within 4 weeks prior to the first dose of study treatment
• Has digestive system diseases may influencing ADME of study drug
• Has a history of severe hypersensitivity reaction, or proven allergic to HS-10516 or its metabolin
• Has any disease or condition would compromise subject safety or interfere with study assessments by investigator's decision