ARTEMIS-001: Phase 1 Study of the HS-20093 in Patients With Advanced Solid Tumors

ARTEMIS-001: A Phase 1, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics, and Efficacy of Multiple Doses of Intravenous Administration of HS-20093 in Patients With Locally Advanced or Metastatic Solid Tumors Who Have Progressed Following Prior Therapy

HS-20093 is a fully 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 safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in Chinese advanced solid tumor patients.

This is a phase 1, open-label, multi-center, dose-escalation and expansion study evaluating the safety, tolerability, pharmacokinetic (PK), and the therapeutic potential of HS-20093 as a monotherapy in subjects with advanced solid tumors.

This is an open-label, multi-center, dose-escalation and expansion, first-in-human phase 1 study in Chinese adult participants with locally advanced or metastatic solid tumors. This study will consist of two parts: A Part Ia dose escalation stage and a Part Ib dose expansion stage.

The objectives of this study are to evaluate the safety, tolerability, PK and preliminary anti-tumor activity, describe the dose-limiting toxicities (DLTs), and determine the maximum tolerated dose (MTD) or maximum administered dose (MAD) of HS-20093.

Part Ia: Participants with advanced cancer are eligible for dose escalation study if they have progressed on or intolerant to available standard therapies, or no standard or available curative therapy exists. The dose escalation will include an initial accelerated titration design followed by i3+3 design.

Part Ib: Enrollment into dose expansion will begin after identification of the MTD or MAD in Phase Ia. The dose expansion study will be conducted in populations with the following indications: locally advanced or metastatic non- small cell lung cancer (NSCLC)，extensive stage small cell lung cancer (ES-SCLC) and other types of advanced solid tumor.

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

Inclusion Criteria:

1. At least age of 18 years at screening;
2. Histologically or cytologically confirmed, locally advanced or metastatic solid tumors for which standard treatment either does not exist or has proven ineffective or unavailable or intolerable
3. At least one extra-cranial measurable lesion according to RECIST 1
4. Agree to provide fresh or archival tumor tissue
5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1
6. 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
   • 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
   • Major surgery within 4 weeks prior to the first scheduled dose of HS-20093

2. Subjects with previous or concurrent malignancies

3. Inadequate bone marrow reserve or organ dysfunction

4. Evidence of cardiovascular risk

5. Evidence of current severe or uncontrolled systemic diseases

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

7. Known active infection requiring antibodies treatment within 2 weeks, or severe infection within 4 weeks prior to the first scheduled dose of HS-20093

8. Subjects with current infectious diseases

9. History of neuropathy or mental disorders

10. Pregnant or lactating female

11. 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

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

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

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