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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Treatment of Her2-positive Muscle-invasive Bladder Cance
• Intervention / Treatment: Drug: RC48- ADC

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 Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 73 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: test group; RC48-ADC 2.0 mg/kg）D1,Triplizumab 3mg/kg D2，Q2W	Drug: RC48- ADC; RC48-ADC 2.0 mg/kg D1,Triplizumab 3mg/kg D2，Q2W; Other Names: Triplizumab

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Tianjin Medical University Cancer Institute and Hospital
• Collaborators: Chongqing University Cancer Hospital; Xiangya Hospital of Central South University; Southwest Hospital, China; Tongji Hospital; Hunan Cancer Hospital; First Affiliated Hospital Xi'an Jiaotong University; Xijing Hospital of Air Force Military Medical University

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2022
• Primary Completion (Anticipated): July 1, 2023
• Study Completion (Anticipated): July 30, 2027

Study Registration Dates

• First Submitted: April 18, 2022
• First Submitted That Met QC Criteria: April 29, 2022
• First Posted (Actual): May 2, 2022

Study Record Updates

• Last Update Posted (Actual): May 2, 2022
• Last Update Submitted That Met QC Criteria: April 29, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Urologic Diseases; Urinary Bladder Diseases; Urinary Bladder Neoplasms
• Other Study ID Numbers: RC48-TA001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Sharing Supporting Information Type: Study Protocol

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No