A Trial of SHR-A2102 With Adebrelimab in Locally Advanced or Metastatic Urothelial Carcinoma

An Open Label, Randomized, Multicenter, Phase III Study of SHR-A2102 in Combination With Adebrelimab Versus Gemcitabine in Combination With Cisplatin/Carboplatin in Previously Untreated Locally Advanced or Metastatic Urothelial Carcinoma (NEC-UC2)

The study is being conducted to evaluate the efficacy of SHR-A2102 with adebrelimab versus gemcitabine in combination with cisplatin/carboplatin in previously untreated locally advanced or metastatic urothelial carcinoma.

Inclusion Criteria:

1. Be able to sign the informed consent form in writing.
2. Female or male, 18 to 80 years of age (both inclusive).
3. ECOG performance status of 0 or 1.
4. Expected survival of≥ 3 months.
5. Histologically confirmed diagnosis of urothelial carcinoma with radiographic or other confirmation of locally advanced unresectable or metastatic disease.
6. No prior systemic therapy for locally advanced or metastatic disease.
7. Able to provide archived or fresh tumor tissue for Nectin-4 and PD-L1 expression.
8. According to RECIST v1.1, there must be at least one measurable lesion;
9. Tolerant to cisplatin or carboplatin.
10. Adequate organ functions.
11. Agree to use medically approved contraceptive measures.

Exclusion Criteria:

1. Planned to receive any other anti-tumor therapy during the study.
2. Received other investigational products or treatments not yet marketed within 4 weeks.
3. Have received systemic anti-tumor treatment within 4 weeks;have received prior anti-tumor Chinese patent medicine treatment within 2 weeks; palliative radiotherapy or local therapy within 2 weeks.
4. Previously received therapy with an antibody-drug conjugate that meets any one of the following characteristics: targeting Nectin-4; containing irinotecan or its derivatives and acting as a topoisomerase I inhibitor.
5. Prior treatment with immune checkpoint inhibitors.
6. Major surgical procedure other than diagnostic or biopsy within 4 weeks, requiring elective surgery during the trial.
7. Active autoimmune disease requiring systemic treatment within 2 years.
8. Have experienced adverse events caused by previous anti-tumor treatments that have not recovered to grade ≤1 as per NCI-CTCAE v5.0.
9. Uncontrolled central nervous system metastases or carcinomatous meningitis.
10. Subjects with clinical symptoms or serous cavity effusion requiring puncture drainage.
11. Other malignancies within 5 years.
12. History of clinically significant pulmonary disease or any such disease suggested by chest imaging at screening.
13. Serious infections requiring intravenous antibiotics, antivirals, or antifungals for control.
14. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
15. History of immunodeficiency, or history of organ transplant.
16. Have experienced arteriovenous thrombosis or cardiovascular and cerebrovascular accidents within 6 months.
17. Subjects with clinically significant hemorrhage within 3 months.
18. Glycosylated hemoglobin (HbA1c) ≥ 8%.
19. Have serious cardiovascular and cerebrovascular diseases.
20. Allergic reaction to any component of the study treatment.
21. Subjects with active pulmonary tuberculosis.
22. History of severe dry eye, active keratitis, or corneal ulcer, or other conditions.
23. Female Subjects who are pregnant or planning to become pregnant during the study.
24. Other conditions unsuitable into the study.