HS-20093 in Patients with Advanced Esophageal Carcinoma and Other Advanced Solid Tumors

A Phase 2, Open-label, Multi-center Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Immunogenicity of HS-20093 in Patients with Advanced Esophageal Carcinoma and Other Advanced Solid Tumors (ARTEMIS-005)

HS-20093 is a humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on solid tumor cells. The objectives of this study are to investigate the anti-tumor activity, safety, pharmacokinetics and immunogenicity of HS-20093 in Chinese advanced esophageal carcinoma and other solid tumor patients.

This is an open-label, multi-center phase 2 study in Chinese adult participants with recurrent, locally advanced or metastatic esophageal carcinoma or other advanced solid tumors, which is designed to investigate the efficacy, safety, pharmacokinetics and immunogenicity of HS-20093. This study will consist of two parts: phase IIa and phase IIb.

Part 1 (phase IIa) will conducted in participants with relapsed, locally advanced or metastatic esophageal carcinoma and other advanced solid tumor. Subjects will receive one dose levels of HS-20093 intravenously every 3 weeks.

Part 2 (phase IIb) will enroll participants with relapsed, locally advanced or metastatic esophageal squamous cell carcinoma. One dose levels of HS-20093 will be administered as an intravenous (IV) infusion every 3 weeks.

Inclusion Criteria:

1. Men or women aged more than or equal to (≥) 18 years.
2. Histologically or cytologically confirmed, relapsed, locally advanced or metastatic esophageal carcinomas and other advanced solid tumor.
3. At least one extra measurable lesion according to RECIST 1.1 (cavity structures such as oesophagus cannot serve as measurable lesions).
4. Agree to provide fresh or archival tumor tissue and blood samples.
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1.
6. Estimated life expectancy >12 weeks.
7. Agree to use medically accepted methods of contraception.
8. Men or women should be using adequate contraceptive measures throughout the study.
9. Females subjects must not be pregnant at screening or have evidence of non-childbearing potential.
10. Signed and dated Informed Consent Form.

Exclusion Criteria:

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

1. 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 Local radiotherapy for palliation within 2 weeks of the first dose of study drug, 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 Major surgery within 4 weeks prior to the first scheduled dose of HS-20093

2. Subjects with previous or concurrent malignancies

3. Significant tumor invasion into adjacent organs (aorta or trachea) of esophageal lesions leading to higher risk of bleeding or fistula

4. Inadequate bone marrow reserve or organ dysfunction.

5. Evidence of cardiovascular risk

6. Evidence of current severe or uncontrolled systemic diseases

7. Evidence of mucosal or internal bleeding within 1 month prior to the first scheduled dose of HS-20093

8. Severe infections occured within 4 weeks before the first dose

9. The presence of active infectious diseases has been known before first dose such as hepatitis B, hepatitis C, ect

10. History of neuropathy or mental disorders

11. Pregnant or lactating female

12. History of severe hypersensitivity reaction, severe infusion reaction or idiosyncrasy to drugs chemically related to HS-20093 or any of the components of HS-20093

13. Known vaccination or hypersensitivity of any level within 4 weeks prior to the first scheduled dose of HS-20093

14. Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator

15. Any disease or condition that, in the opinion of the investigator, would compromise subject safety or interfere with study assessments