ARTEMIS-003: HS-20093 in Patients With Metastatic Castrate-resistant Prostate Cancer (mCRPC) and Advanced Solid Tumors

This is a phase 2, open-label, multi-center study consisting of two parts: Phase 2a and 2b.

Phase 2a: The study will be conducted in the following two cohorts: Cohort 1: Patients with metastasis castration resistant prostate cancers who have progressed on or intolerant to standard therapies. Cohort 2: Other patients with advanced solid tumor if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. All subjects will receive 8 mg/kg of HS-20093.

Phase 2b: The study will be conducted in patients with metastasis castration resistant prostate cancers who have progressed on or intolerant to standard therapies. Subjects will receive 8 mg/kg of HS-20093.

All patients will be carefully followed for adverse events during the study treatment and for 90 days after the last dose of HS-20093. Subjects will be permitted to continue therapy with assessments for progression if the product is well tolerated and sustained clinical benefit exists.

Inclusion criteria

• Subjects eligible for inclusion in this study must meet all of the following criteria:

• Men or women greater than or equal to 18 years.
• Locally advanced or metastatic solid tumors confirmed by histology or cytology, for which standard treatment is invalid, unavailable or intolerable.
• At least one measurable lesion in accordance with RECIST 1.1.
• Agree to provide fresh archival tumor tissue.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1.
• Estimated life expectancy ≥ 12 weeks.
• Men or women should be using adequate contraceptive measures throughout the study.
• Female subjects must not be pregnant at screening or have evidence of non-childbearing potential.
• Signed and dated Informed Consent Form.

Exclusion criteria

• Any of the following would exclude the subject from participation in the study:

• Treatment with any of the following:

Previous or current treatment with B7-H3 targeted therapy. Any cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093. Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093.

Radiotherapy with a limited field of radiation for palliation within 2 weeks, or patients received more than 30% of the bone marrow irradiation, or large-scale radiotherapy within 4 weeks prior to the first scheduled dose of HS-20093.

Pleural or peritoneal effusion requiring clinical intervention. Pericardial effusion.

Major surgery within 4 weeks prior to the first scheduled dose of HS-20093. Spinal cord compression or brain metastases. Treatment with drugs that are predominantly strong inhibitors or inducers or sensitive substrates of CYP3A4, CYP2D6, P-gp or BCRP with a narrow therapeutic range within 7 days of the first dose of study drug; or requiring treatment with these drugs during the study.

Currently receiving drugs known to prolong QT interval or may cause torsade de pointe; or requiring treatment with these drugs during the study

• Patients with BRCA and ATM mutation.
• Any unresolved toxicities from prior therapy greater than Grade 2 according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0 with the exception of alopecia or neurotoxicity
• History of other primary malignancies.
• Inadequate bone marrow reserve or organ dysfunction.
• Evidence of cardiovascular risk.
• Severe, uncontrolled or active cardiovascular diseases.
• Severe or uncontrolled diabetes, including diabetes ketoacidosis or hyperglycemia hypertonic occurring within 6 months before the first dose of the study drug, or the glycosylated hemoglobin value ≥ 7.5% in the screening period.
• Severe or poorly controlled hypertension.
• Bleeding symptoms with apparent clinical significance or obvious bleeding tendency within 1 months prior to the first dose of HS-20093
• Serious arteriovenous thrombosis events occurred within 3 months before the first dose
• Severe infections occurred within 4 weeks before the first dose
• Patients who have received continuous steroid treatment for more than 30 days within 30 days before the first dose, or need long-term (≥ 30 days) steroid treatment, or who have other acquired and congenital immunodeficiency diseases, or have a history of organ transplantation
• The presence of active infectious diseases before the first dose such as hepatitis B, hepatitis C, tuberculosis, syphilis, or human immunodeficiency virus HIV infection, etc.
• Hepatic encephalopathy, hepatorenal syndrome, or Child-Pugh Grade B or more severe cirrhosis
• Other moderate or severe urinary diseases that may interfere with the detection or treatment of drug-related urinary toxicity or may seriously affect urinary function.
• History of serious neuropathy or mental disorders.
• Women who are breastfeeding or pregnant or planned to be pregnant during the study period.
• Vaccination or hypersensitivity of any level within 4 weeks prior to the first dose of HS-20093
• History of severe hypersensitivity reaction, severe infusion reaction or allergy to recombinant human or mouse derived proteins
• Hypersensitivity to any ingredient of HS-20093
• Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.
• Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments.