An Open-label, Single-arm, Multicenter Phase II Clinical Study： Evaluating RC48-ADC Combined With Triplizumab in the Neoadjuvant Treatment of Her2-positive Muscle-invasive Bladder Cancer

Phase 2

Not yet recruiting

• Conditions: Neoadjuvant Treatment of Her2-positive Muscle-invasive Bladder Cance
• Interventions: Drug: RC48- ADC

• Registration Number: NCT05356351
• Lead Sponsor: Tianjin Medical University Cancer Institute and Hospital

Brief Summary

An Open-label, Single-arm, Multicenter Phase II Clinical Study： Evaluating RC48-ADC Combined With Triplizumab in the Neoadjuvant Treatment of Her2-positive Muscle-invasive Bladder Cancer.It's arm to evaluate the neoadjuvant treatment of Her2-positive Muscle-invasive Bladder Cancer in patients with objective response rate (ORR),Duration of response (DoR) , progression-free survival (PFS), overall survival (OS), and safety.

Detailed Description

Objective response rate (ORR), Duration of response (DoR) (according to RECIST 1.1 Standard Edition)，progression-free survival (PFS), overall survival (OS), quality of life (QoL)and safety. Evaluation once every 2 weeks before cystectomy, If the efficacy results of the evaluation are complete response (CR) or partial response (PR), confirmed imaging efficacy at 9 weeks after the initial assessment ， efficacy evaluation time window of ± 14 days.

Study Timeline

• Status Verified: 2022-02
• Study First Submitted: 2022-04-18
• Study First Submitted QC: 2022-04-29
• Last Update Submitted: 2022-04-29
• Study Start: 2022-05-01
• Study First Posted: 2022-05-02
• Last Update Posted: 2022-05-02
• Primary Completion: 2023-07-01
• Study Completion: 2027-07-30

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

1. The subject is volunteer to participate, and the subject must signed an informed consent form (ICF), indicating that it understands the purpose of this study and the required procedures, and is willing to participate in the study. Subjects must be willing and abide by prohibition and restrictions specified in the research program; Subjects are willing and able to follow the trial and follow-up procedures

2. Patients with invasive bladder cancer are prepared for radical cystectomy (standard lymph node dissection);

3. Age ≥ 18 years old and ≤ 75 years old;

4. Clinical stage T2-T4aN0M0 (assessed by CT/MR/PET-CT);

5. Pathological was confirmed urothelial carcinoma by TURBT, HER2 overexpression confirmed by pathological biopsy: IHC2+ or IHC3+(central laboratory verification) andthe physical condition was not suitable for neoadjuvant chemotherapy ( pathological permit urothelial carcinoma Combined with other variant subtypes, with urothelial carcinoma as the main type) or refused neoadjuvant chemotherapy;

6. ECOG score ≤ 1;

7. After TURBT, residual tumor (measurable according to RECIST 1.1 criteria) is present;

8. The important laboratory examination indexes meet the following requirements:

   1. Hemoglobin ≥ 90g/L.
   2. Absolute neutrophil count (ANC) ≥ 1.5 × 109 / L.
   3. Platelet ≥ 100 × 109 / L.
   4. 3.5mmol/L ≤ serum potassium ≤ 5.5mmol/L.
   5. Liver function index: ALT, AST ≤ 1.5 times the upper limit of normal value (ULN), TBIL ≤ 1.5ULN.
   6. Subjects with Serum creatinine≤ 1.5× ULN
   7. The left ventricular ejection fraction (LVEF) was 50%.

9. Female subjects should be surgically sterilized or postmenopausal, or agree to use at least one medically approved contraceptive method (such as intrauterine device, contraceptive or condom) during the study treatment and within 6 months after the end of the study treatment period. The blood pregnancy test must be negative within 7 days before the study, and it must be non-lactation. Male subjects should agree to use at least one medically approved contraceptive method (such as condoms, abstinence, etc.) during the study treatment period and within 6 months after the end of the study treatment period.

Exclusion Criteria

1. Had received live attenuated vaccine or had serious infection or planned to receive any vaccine during the study period4 weeks before entering the group.
2. Received antineoplastic therapy within 6 months before the start of the study, including chemotherapy, radiotherapy, targeted therapy, immunotherapy and clinical research antineoplastic drug therapy.
3. Uncontrollable concomitant diseases, including, but not limited to, persistent infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, arrhythmia, interstitial lung disease, severe chronic gastrointestinal disease associated with diarrhoea, or mental illness / social conditions, which will limit compliance with research requirements, significantly increase the risk of AE or impair the patient's ability to write informed consent.The results of HIVAb test were positive;with active bleeding or new thrombotic disease who are taking therapeutic anticoagulants or who have a tendency to bleed
4. Patients with RC48-ADC /PD-1 allergy or hypersensitivity, patients with autoimmune diseases;
5. HBsAg or HBcAb test results are positive, while HBVDNA copies are positive; HCVAb test results are positive (only if the PCR test result of HCVRNA is negative);Systemic corticosteroids or other systemic immunosuppressive drugs are used before enrollment, or systemic immunosuppressive drugs are expected to be needed during the trial;
6. Serious arteriovenous thrombosis or cardio-cerebrovascular accidents occurred within 1 year before administration, such as deep venous thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc., except for lacunar infarction that is asymptomatic and does not require clinical intervention;with active bleeding or new thrombotic disease who are taking therapeutic anticoagulants or who have a tendency to bleed.
7. Active/known/suspected autoimmune disease, history of primary immunodeficiency,Previous allogeneic hematopoietic stem cell transplantation;
8. Diagnosed with other malignancies within 5 years
9. Pregnant or lactating women.
10. Patients with missing main observation indicators, incomplete research data, incomplete follow-up data or failure to follow the research protocol

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
test group	RC48- ADC	RC48-ADC 2.0 mg/kg）D1,Triplizumab 3mg/kg D2，Q2W

Primary Outcome Measures

Name	Time	Method
Incidence of adverse events and serious adverse events	Up to approximately 6 months	safety
Pathological response (PaR) rate	Up to approximately 6 months	Pathological response (PaR) rate per central pathology review
recommended dose for phase II safety (RP2D)	Up to approximately 6 months	tolerability

Secondary Outcome Measures

Name	Time	Method
Progression free survival	Up to approximately 24 months	Follow-up was made after the first month after the operation, and then with an every three months until the tumor relapsed or progress
Overall survival	Up to approximately 48 months	The time from start of study treatment to date of death due to any cause
Duration of response	Up to approximately 24 months	This is the time from when the tumor begins to respond to treatment until the disease gets worse
The pathological complete response	Up to approximately 6 months	The pathological complete response rate refers to all target lesions disappear