Clinical trial NCT06738251: A Phase III Study of SHR-A2102 Versus Investigator-selected Therapy in Advanced Urothelial Carcinoma
Official title: A Randomized, Open-label, Controlled, Multicenter Phase III Clinical Study of SHR-A2102 for Injection Versus Investigator-selected Therapy in Locally Advanced or Metastatic Urothelial Carcinoma Previously Treated With Platinum-Containing Chemotherapy and PD-(L)1 Inhibitors and With or Without ADC
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Advanced Urothelial Carcinoma
Lead sponsor: Shanghai Hengrui Pharmaceutical Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2024-12-17
Enrollment: 402
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: To evaluate the efficacy and safety of SHR-A2102 for injection versus Investigator-selected Therapy in patients with Locally advanced or Metastatic Urothelial Carcinoma who have been previously treated with platinum-based chemotherapy and PD-(L)1 inhibitors.


Eligibility criteria: Inclusion Criteria:

1. Voluntarily participate in this clinical study, understand the study procedures and be able to sign the informed consent form in writing.
2. 18 to 80 years old (including boundary value), gender is not limited.
3. ECOG performance status score of 0 or 1.
4. Estimated survival ≥ 3 months.
5. Pathologically confirmed urothelial carcinoma confirmed by imaging or other methods as locally advanced unresectable or metastatic disease.
6. For locally advanced or metastatic disease, prior treatment with platinum-containing chemotherapy and PD-(L)1 inhibitors; Patients who have been treated with platinum-containing chemotherapy and/or PD-(L)1 inhibitors during neoadjuvant/adjuvant therapy and who have relapsed or progressed during treatment or within 6 months of the end of treatment may also be enrolled.
7. Imaging-confirmed disease progression during or after treatment with the most recent regimen.
8. Able to provide preserved or fresh tumor tissue.
9. Must be present with at least one measurable lesion according to RECIST v1.1 criteria.
10. Good level of organ function.
11. Male subjects whose partners are women of childbearing potential and female subjects of childbearing potential must use highly effective contraception from the time of signing the informed consent form until 8 months after the last dose of the trial drug.

Exclusion Criteria:

1. Planned to receive any other anti-tumor therapy during this trial.
2. Receipt of other unmarketed clinical trial drugs or treatments within 4 weeks prior to randomization.
3. Received systemic anti-tumor therapy such as chemotherapy, radiotherapy, biological therapy, targeted therapy, or immunotherapy within 4 weeks prior to randomization, and palliative radiotherapy or local therapy within 2 weeks prior to the first use of the investigational drug.
4. Prior receipt of antibody-drug conjugates containing topoisomerase I inhibitors in the composition.
5. Prior treatment with more than 1 line of chemotherapy.
6. Prior treatment with more than 1 antibody-drug conjugate.
7. Major surgery other than diagnosis or biopsy within 4 weeks prior to randomization that requires elective surgery during the trial.
8. Received systemic glucocorticoids (prednisone \> 10 mg/day or equivalent dose) or other immunosuppressants within 14 days prior to the first use of investigational drug or randomization for immunosuppressive purposes.
9. Adverse events from prior antineoplastic therapy did not recover to Grade ≤1 according to NCI-CTCAE v5.0.
10. Inadequately treated central nervous system (CNS) metastases, or the presence of uncontrolled or symptomatic active central nervous system metastases. CNS metastases that have been adequately treated and whose neurological symptoms are able to return to baseline at least 4 weeks prior to randomization (with the exception of residual signs or symptoms associated with CNS treatment) may be enrolled in the study.
11. Subject has a serous effusion with clinical symptoms or requiring puncture and drainage.
12. Any other malignancy within 5 years prior to randomization (since the last anti-tumor therapy), excluding cured basal cell carcinoma of the skin and carcinoma in situ of the cervix, etc.
13. Previous history of clinically significant pulmonary disease (e.g., interstitial pneumonia, radiation pneumonitis, pulmonary fibrosis) or chest imaging suggestive of any such disease during the screening period.
14. Severe infections requiring intravenous antibiotics, antivirals, or antifungals for control.
15. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
16. Has a history of immunodeficiency or organ transplantation.
17. Arterior/venous thrombotic events such as cerebrovascular accident, deep vein thrombosis and pulmonary embolism occurred within 6 months before the first study drug.
18. Those who have had significant clinically significant bleeding symptoms within 3 months before the first study drug.
19. Glycosylated hemoglobin (HbA1c) ≥8%.
20. Have severe cardiovascular and cerebrovascular diseases.
21. Allergic reaction to any component of this study treatment.
22. Female subjects who are pregnant or plan to become pregnant during the study.
23. According to the judgment of the investigator, there are concomitant diseases (such as thyroid disease and mental illness, etc.) or any other conditions that seriously endanger the safety of the patient, or affect the patient's completion of this study.

Primary outcomes:
measure: Progression-free Survival (PFS)
timeFrame: Up to approximately 1.5 years.
measure: Overall Survival (OS)
timeFrame: Up to approximately 1.5 years and 2 years.
Secondary outcomes:
measure: Objective Response Rate (ORR)
timeFrame: Up to approximately 1.5 years and 2 years.
measure: Disease Control Rate (DCR)
timeFrame: Up to approximately 1.5 years and 2 years.
measure: Duration of Response (DoR)
timeFrame: Up to approximately 1.5 years and 2 years.
measure: Serum concentrations of SHR-A2102
timeFrame: Up to approximately 2 years.
measure: Serum concentrations of SHR-A2102 toxin
timeFrame: Up to approximately 2 years.
measure: Anti-SHR-A2102 antibody (ADA)
timeFrame: Up to approximately 2 years.
measure: Anti-SHR-A2102 neutralizing antibody (NAb)
timeFrame: Up to approximately 2 years.
measure: Incidence and severity of adverse event (AE)
timeFrame: Up to approximately 2 years.
measure: Incidence and severity of serious adverse event (SAE)
timeFrame: Up to approximately 2 years.
Other outcomes:
Locations:
city: Beijing
country: China
facility: Beijing Cancer Hospital
state: Beijing
Study officials:
References: