SHR-A2102 plus adebrelimab versus platinum-based chemotherapy for advanced 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)

This test compares SHR-A2102 combined with adebrelimab to gemcitabine with cisplatin or carboplatin in people with previously untreated locally advanced or metastatic urothelial carcinoma.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 462 (estimated)
• Ages: 18 Years to 80 Years
• Sex: All
• Sponsor: Suzhou Suncadia Biopharmaceuticals Co., Ltd. (Industry-sponsored)
• Drugs / interventions: adebrelimab
• Locations: 1 site (Beijing, Beijing Municipality)
• Trial ID: NCT07393542 on ClinicalTrials.gov

What this trial studies

This Phase 3 interventional trial compares a combination therapy of SHR-A2102 and the anti–PD-L1 antibody adebrelimab against standard platinum-based chemotherapy (gemcitabine with cisplatin or carboplatin) in patients with untreated locally advanced or metastatic urothelial carcinoma. Eligible participants must have measurable disease, be cisplatin- or carboplatin-tolerant, have ECOG performance status 0–1, and provide tumor tissue for Nectin-4 and PD-L1 testing. The trial is sponsored by Suzhou Suncadia Biopharmaceuticals and is being conducted at Beijing Cancer Hospital. The primary focus is on clinical benefit with biomarker collection to explore response predictors.

Who should consider this trial

Good fit: Ideal candidates are adults (18–80) with histologically confirmed locally advanced unresectable or metastatic urothelial carcinoma who have not received prior systemic therapy for advanced disease, have ECOG 0–1, measurable disease, adequate organ function, are cisplatin/carboplatin tolerant, and can provide tumor tissue for biomarker testing.

Not a fit: Patients who have received prior systemic therapy for advanced disease, have ECOG ≥2, significant organ dysfunction, are ineligible for platinum chemotherapy, or cannot provide required tumor tissue are unlikely to qualify or benefit from this protocol.

Why it matters

Potential benefit: If successful, the combination could improve response rates or survival compared with standard chemotherapy and offer a targeted plus immune therapy option for these patients.

How similar studies have performed: Related approaches combining Nectin-4–targeting agents or antibody–drug conjugates with PD-(L)1 inhibitors have shown clinical activity in urothelial carcinoma, but this exact SHR-A2102 plus adebrelimab combination is novel at the Phase 3 level.

Eligibility criteria

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. Have 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.

Where this trial is running

Beijing, Beijing Municipality

• Beijing Cancer Hospital — Beijing, Beijing Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chun Yang

Conditions Locally Advanced or Metastatic Urothelial Carcinoma