ARTEMIS-103: Phase 1b Study of HS-20093 Combinations in Patients with Bone and Soft Tissue Sarcoma.

ARTEMIS-103: a Phase 1b, Open-label, Multi-center Study to Evaluate Safety, Tolerability, Pharmacokinetics and Efficacy of Intravenous Administration of HS-20093 in Combination with Other Anti-cancer Agents in Patients with Bone and Soft Tissue Sarcoma.

HS-20093 is a fully humanized IgG1 antibody-drug conjugate (ADC) which specifically binds to B7-H3, a target wildly expressed on bone and soft tissue sarcoma. The objectives of this study are to investigate the safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents in patients with advanced bone and soft tissue sarcoma.

This is a phase 1b, open-label, multi-center, dose-escalation and expansion study in subjects with advanced bone and soft tissue sarcoma. This study is in design allowing assessment of safety, tolerability, pharmacokinetics and anti-tumor activity of HS-20093 in combination with other anti-cancer agents.

A total of 4 combination-treatments will be carried out in 2 cohorts. The target population in cohort 1 of dose escalation part is soft tissue sarcoma patients have progressed on or intolerant to available standard therapies, and the dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease. The target population in cohort 2 will enroll patients with osteosarcoma have progressed on or intolerant to available standard therapies 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:

• At least age of 18 years at screening;

• Histologically or cytologically confirmed, locally advanced or metastatic osteosarcoma and soft tissue sarcoma

  1. Cohort1: Dose escalation part will enroll advanced soft tissue sarcoma for which standard treatment has proven ineffective or unavailable or intolerable. Dose expansion part will enroll patients who have not received prior treatment for advanced/metastatic disease.
  2. Cohort2: Advanced osteosarcoma patients for which standard treatment has proven ineffective or unavailable or intolerable.

• least one extra-cranial measurable lesion according to RECIST 1

• Agree to provide fresh or archival tumor tissue

• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0~1

• Life expectancy >= 12 weeks

• Agree to use medically accepted methods of contraception

• Men or women should be using adequate contraceptive measures throughout the study;

• Females subjects must not be pregnant at screening or have evidence of non-childbearing potential

• Signed and dated Informed Consent Form

Exclusion Criteria:

• treatment with any of the following:

  1. Previous or current treatment with B7-H3 targeted therapy
  2. Previous or current treatment with TOP1i related treatment
  3. Previous or current treatment with PD-L1 inhibitor (Cohort2 )
  4. Intolerable for any Anlotinib(Cohort 1a/1c), Anthracyclines (Cohort 1b/1c) and PD-L1 inhibitor (Cohort2 )
  5. Cytotoxic chemotherapy, investigational agents and anticancer drugs within 14 days prior to the first scheduled dose of HS-20093
  6. Prior treatment with a monoclonal antibody within 28 days prior to the first scheduled dose of HS-20093
  7. 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
  8. Major surgery within 4 weeks prior to the first scheduled dose of HS-20093

• Subjects with previous or concurrent malignancies

• Inadequate bone marrow reserve or organ dysfunction

• Evidence of cardiovascular risk

• Evidence of current severe or uncontrolled systemic diseases

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

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

• Subjects with current infectious diseases

• History of neuropathy or mental disorders

• Pregnant or lactating female

• 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

• 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