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

Official title

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)

Overview

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.

Interventions

• Drug SHR-A2102 and Adebrelimab
  SHR-A2102 and Adebrelimab injection
• Drug Gemcitabine and cisplatin / carboplatin
  Gemcitabine injection and cisplatin injection / carboplatin injection

Primary outcome measures

• Progression-free survival(PFS), assessed by BICR [Time frame: up to 50 months]

Secondary outcome measures (11)

• Determine the dose of SHR-A2102 in the second phase, participants included in the dose selection analysis were followed up at 6 months in the last case [Time frame: Determine the dose of SHR-A2102 in the second phase, participants included in the dose selection analysis were followed up at 6 months in the last case]
• Overall Survival(OS) [Time frame: up to 50 months]
• Objective response rate(ORR), assessed by BICR [Time frame: up to 50 months]
• Disease control rate(DCR), assessed by BICR [Time frame: up to 50 months]
• Duration of response(DoR), assessed by BICR [Time frame: up to 50 months]
• PFS, assessed by investigator [Time frame: up to 50 months]
• ORR, assessed by investigator [Time frame: up to 50 months]
• DCR, assessed by investigator [Time frame: up to 50 months]
• DoR, assessed by investigator [Time frame: up to 50 months]
• Adverse event(AE) [Time frame: up to 50 months]
• serious adverse event(SAE) [Time frame: up to 50 months]

Eligibility criteria

Inclusion criteria

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

Exclusion criteria

• Planned to receive any other anti-tumor therapy during the study.
• Received other investigational products or treatments not yet marketed within 4 weeks.
• 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.
• 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.
• Prior treatment with immune checkpoint inhibitors.
• Major surgical procedure other than diagnostic or biopsy within 4 weeks, requiring elective surgery during the trial.
• Active autoimmune disease requiring systemic treatment within 2 years.
• Have experienced adverse events caused by previous anti-tumor treatments that have not recovered to grade ≤1 as per NCI-CTCAE v5.0.
• Uncontrolled central nervous system metastases or carcinomatous meningitis.
• Subjects with clinical symptoms or serous cavity effusion requiring puncture drainage.
• Other malignancies within 5 years.
• History of clinically significant pulmonary disease or any such disease suggested by chest imaging at screening.
• Serious infections requiring intravenous antibiotics, antivirals, or antifungals for control.
• Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection.
• History of immunodeficiency, or history of organ transplant.
• Have experienced arteriovenous thrombosis or cardiovascular and cerebrovascular accidents within 6 months.
• Subjects with clinically significant hemorrhage within 3 months.
• Glycosylated hemoglobin (HbA1c) ≥ 8%.
• Have serious cardiovascular and cerebrovascular diseases.
• Allergic reaction to any component of the study treatment.
• Subjects with active pulmonary tuberculosis.
• Have severe dry eye, active keratitis, or corneal ulcer, or other conditions.
• Female Subjects who are pregnant or planning to become pregnant during the study.
• Other conditions unsuitable into the study.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Beijing Cancer Hospital — Beijing

Identifiers

NCT: NCT07393542 · SHR-A2102-302

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗