Study of HS-10516 Combination Therapy in Patients With Advanced Renal Cell Carcinoma

Prior treatment

• Prior or Current Treatments:
  • Previous or current use of hypoxia-inducible factor inhibitors.
  • Previous or current use of lenvatinib.
  • Use of Chinese herbal medicine with antitumor indications within 2 weeks prior to the first dose or requirement for such treatment during the study.
  • Administration of cytotoxic chemotherapy or other systemic antitumor therapies (e.g., endocrine therapy, molecular targeted therapy) within 2 weeks or 5 half-lives (whichever is shorter) prior to the first dose, or requirement for such treatments during the study.
  • Use of large-molecule antitumor drugs within 4 weeks prior to the first dose or requirement for such treatment during the study.
  • Use of CYP2C19 strong inhibitors/inducers or narrow therapeutic index sensitive substrates within 7 days prior to the first dose, or requirement for continued use during the study.
  • Local radiotherapy (except brain radiotherapy; see Criterion 6) within 2 weeks prior to the first dose, or \>30% bone marrow irradiation/large-field radiotherapy within 4 weeks prior to the first dose.
  • Major surgery (e.g., craniotomy, thoracotomy, laparotomy; Grade 3/4 per Chinese Medical Technical Clinical Application Regulations) within 4 weeks prior to the first dose.
  • Participation in other interventional clinical trials within 4 weeks prior to the first dose or within 5 half-lives of investigational drugs (whichever is longer).
• Severe pulmonary dysfunction requiring intermittent/long-term oxygen therapy.
• Unresolved Grade \>1 toxicities from prior anti-tumor therapy (per CTCAE v5.0).

Other illness

• History of second primary malignancy.
• Known or suspected active CNS metastases/leptomeningeal disease.
• Severe, uncontrolled, or active cardiovascular disease.
• Severe or poorly controlled diabetes.
• Severe or poorly controlled hypertension.

Other

• Resting pulse oximetry \<92% at screening.
• Inadequate bone marrow reserve or serious organ dysfunction.

• Men or women aged more than or equal to (≥) 18 years.
• Histologically confirmed unresectable, locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) with disease progression during or after receiving ≥1 prior line of systemic therapy in the advanced setting.
• Patients have at least one target lesion according to RECEST 1.1. The requirements for target lesions are: measurable lesions without local treatment such as irradiation, or with definite progress after local treatment, with the longest diameter ≥ 10 mm in the baseline period (in case of lymph nodes, the shortest axis ≥ 15 mm is required). Patients with only brain and/or bone lesions as target lesions will not be included.
• ECOG performance status was 0-1 and did not deteriorate in the previous 2 weeks.
• Estimated life expectancy greater than (\>) 12 weeks.
• Reproductive-age women agree to use adequate contraception and cannot breastfeed while participating in this study and for a period of 12 months after the last dose. Likewise, men also consent to use adequate contraceptive method within the same time limit.
• Females must have the evidence of non-childbearing potential
• Sign informed consent form.