A Study of SHR-A1921 for Injection in Subjects With Advanced Solid Tumours

A Phase 1 Multi-Center, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of SHR-A1921 in Subjects With Advanced Malignant Solid Tumour .

To assess the safety and tolerability of SHR-A1921 in patients with advanced solid tumours, to determine the dose-limiting toxicity (DLT), maximum tolerated dose (MTD), and/or recommended phase II dose (RP2D) of SHR-A1921

Inclusion Criteria:

1. Voluntary participation and written informed consent；
2. Aged 18-75 years (inclusive), males and females;
3. Consents to provide tumor tissue samples;
4. Subjects must have histologically or clinically confirmed advanced and/or metastatic malignancies for which failure of standard treatment or lack of effective standard treatment;
5. At least one measurable lesion according to RECIST v1.1;
6. ECOG score of 0-1;
7. Expected survival ≥ 12 weeks;
8. Adequate bone marrow reserve and organ function ；
9. For female patients of childbearing potential or male patients with partners of childbearing potential who are not sterilized by surgical operations, they are required to use a medically approved contraceptive measure during the study treatment period and within 3 months after the end of the study treatment; For female patients of childbearing potential who are not sterilized by surgical operations, they must have a negative serum HCG test result within 72 h prior to study enrollment; and they must not be in the lactation period;

Exclusion Criteria:

1. Known and untreated central nervous system (CNS) or leptomeningeal metastases;
2. Macrovascular invasion based on imaging;
3. Cancerous ascites, pleural effusion or pericardial effusion with clinical symptoms;
4. Has a history of a second malignancy;
5. History of immunodeficiency disease or organ transplant;
6. Uncontrolled cardiac diseases or symptoms;
7. Has a history of non-infectious ILD/pneumonitis that required steroids, or has current ILD/pneumonitis;
8. Has a history of active chronic enteritis 6 weeks prior to the initiation of the study treatment or intestinal obstruction, gastrointestinal perforation 3 months prior to the initiation of the study treatment;
9. Has a history of Grade≥2 bleeding 4 weeks prior to the initiation of the study treatment or is current receiving anticoagulation therapy;
10. Subjects with active hepatitis B or active hepatitis C;
11. Subjects who have received systemic anti-tumor treatments 4 weeks prior to the initiation of the study treatment.
12. Has unresolved toxicities from previous anticancer therapy.
13. Has a history of severe hypersensitivity reactions to either the drug substances or inactive ingredients of SHR-A1921;
14. Subjects with other potential factors that may affect the study results or result in the premature discontinuation as determined by the investigator, such as alcoholism, drug abuse, other serious diseases (including mental illness) requiring concomitant treatment, serious laboratory abnormalities, or family or social factors that could affect the safety of the patients.