A Trial of SHR-A2102 With Antitumor Therapy in Advanced Urothelial Carcinoma

Recruitment & Eligibility

Inclusion Criteria

Competent to comprehend, sign, and date an informed consent form.
Male or female subjects must be age 18 or older.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Subjects must have histologically documented, unresectable locally advanced or
Histologically confirmed locally advanced or metastatic urothelial cancer.Phase Ib, subjects must have failed, be intolerant or refused the standard treatment; Phase II, subjects must not have received systemic antitumor therapy for locally advanced unresectable or metastatic urothelial carcinoma.
An archival tumor tissue sample or a fresh tissue sample should be provided.
Subjects must have measurable disease according to RECIST (version 1.1).

Exclusion Criteria

Subjects with not adequately treated, or uncontrollable , or active CNS metastases.
Subjects who have previously received TOPO1-based ADCs.
Subjects who have received anti-cancer treatment within 4 weeks prior the first dose of study treatment.
Subjects who have received radiotherapy within 14 days , or chest radiotherapy > 30Gy within 6 months prior to the first dose of study drug.
Subjects with ongoing clinically significant toxicity associated with prior treatment that has not resolved to ≤ Grade 1.
Subjects who have received systemic immunosuppressant treatment within 14 days prior the first dose of study treatment.
Subjects who have known or suspected interstitial pneumonitis.
Phase Ib: Subjects who have had≥ Grade 3 irAEs during the previous treatment with ICIs.
Subjects who have any active, known or suspected autoimmune diseases.
Subjects who have moderate or severe ascites with clinical symptoms, or uncontrolled or moderate or above pleural effusion, or pericardial effusion.
Subjects who have uncontrolled cardiac diseases or cardiac clinical symptoms.

Study & Design

Arm && Interventions

Group	Intervention	Description
SHR-A2102 + Adebrelimab injection+SHR-8068 injection	SHR-A2102	-
SHR-A2102 + Adebrelimab injection+SHR-8068 injection	Adebrelimab injection	-
SHR-A2102 + Adebrelimab injection+SHR-8068 injection	SHR-8068 injection	-

Primary Outcome Measures

Name	Time	Method
Phase II: ORR by investigator assessment	Up to approximately 5 years
Phase I: RP2D of SHR-A2102 combined with Adebrelimab and SHR-8068 in patients with advanced urothelial cancer	Up to approximately 5 years
Phase I: Incidence and severity of adverse events	Up to approximately 5 years

Secondary Outcome Measures

Name	Time	Method
Phase I: ORR by investigator assessment	Up to approximately 5 years
Phase I: PFS by investigator assessment	Up to approximately 5 years
Phase II: Incidence and severity of adverse events	up to 5 years
Phase I: Pharmacokinetic parameter for serum concentrations of SHR-A2102 and free toxin	Up to approximately 5 years
Phase II: DCR by investigator assessment	Up to approximately 5 years
Phase I: DCR by investigator assessment	Up to approximately 5 years
Phase I: DoR by investigator assessment	Up to approximately 5 years
Phase I: OS by investigator assessment	Up to approximately 5 years
Phase I: Anti-SHR-A2102 antibody (ADA) and anti-SHR-A2102 neutralizing antibody (NAb)	Up to approximately 5 years
Phase II: DoR by investigator assessment	Up to approximately 5 years
Phase II: PFS by investigator assessment	Up to approximately 5 years
Phase II: OS by investigator assessment	Up to approximately 5 years
Phase II: Pharmacokinetic parameter for serum concentrations of SHR-A2102 and free toxin	Up to approximately 5 years
Phase II: Anti-SHR-A2102 antibody (ADA) and anti-SHR-A2102 neutralizing antibody (NAb)	Up to approximately 5 years

Recruitment & Eligibility