HS-20093 in Patients With Advanced Gastric and Gastroesophageal Junction Adenocarcinoma

Prior treatment

• Any unresolved toxicities from prior therapy greater than Grade 1 according to CTCAE 5.0 or baseline status.
• Major surgery within 4 weeks prior to the first scheduled dose of HS-20093.
• Active infection requiring therapeutic intravenous antibiotics within 2 weeks prior to the first dose.
• Clinically significant bleeding symptoms or marked hemorrhagic tendency within 1 month prior to the first dose of HS-20093.
• Serious arterial or venous thromboembolic events occurring within 3 months prior to the first dose of HS-20093.
• History of active or prior autoimmune disease requiring systemic treatment.
• Requires long-term glucocorticoid therapy.
• Having undergone any major surgery within 4 weeks prior to the first dose.
• Vaccination within 4 weeks prior to the first dose of HS-20093.
• Previous history of serious neurological or mental disorders. Unlikely to comply with study procedures, restrictions, and requirements in the opinion of the investigator.

Other illness

• History of other primary malignancies
• Severe, uncontrolled or active cardiovascular diseases.
• Severe or poorly controlled hypertension.
• Severe or poorly controlled diabetes.
• Poorly controlled cancer-related pain.
• The presence of active infectious diseases has been known: hepatitis B, hepatitis C and HIV.
• Active tuberculosis.
• History of known interstitial pneumonia or immune-mediated pneumonitis.
• Current hepatic encephalopathy, hepatorenal syndrome, or cirrhosis ≥ Child-Pugh class B.
• History of severe allergy.

Lab values

• Treatment with any of the following:
  • Previous or current treatment with B7-H3 targeted therapy.
  • Previous or current treatment with topoisomerase I inhibitors.
  • 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
  • Treatment with drugs that are predominantly CYP3A4 strong inhibitors or inducers or sensitive substrates of CYP3A4 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.

Other

• Histology shows squamous cell carcinoma, undifferentiated carcinoma, or mixed tumors , such as adenosquamous carcinoma or other mixed tumors.
• Presence of pleural effusion/ascites requiring clinical intervention.
• Newly diagnosed brain metastases without treatment, or brain metastases that have not achieved stability despite treatment; presence of leptomeningeal metastasis or brainstem metastasis; presence of spinal cord compression.
• Evidence of cardiovascular risk.
• Severe malnutrition.
• Currently enrolled in or participating in any other clinical study involving investigational interventions or other types of interventional medical research.

• At least age of 18 years at screening, with no restrictions on gender.
• Signed and dated Informed Consent Form.
• Participants with pathologically or cytologically confirmed locally advanced unresectable or metastatic GC/GEJC, who have failed, or intolerant to standard therapies.
• At least one extra measurable lesion according to RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0\~1.
• Estimated life expectancy \>12 weeks.
• Agree to provide fresh or archival tumor tissue.
• Good organ function.
• Female subjects must not be pregnant at screening or have evidence of non-childbearing potential.
• Men or women should be using adequate contraceptive measures throughout the study.