RC48 Combined With Tislelizumab for Bladder Sparing Treatment in NMIBC With BCG Treatment Failure and HER2 Expression

RC48 Combined With Tislelizumab for Bladder Sparing Treatment in High-risk Non-muscular Invasive Bladder Cancer (NMIBC) With BCG Treatment Failure and HER2 Expression

RC48 Combined With Tislelizumab for Bladder Sparing Treatment in NMIBC With BCG Treatment Failure and HER2 Expression (NCT05957757) is a Phase 2 interventional studying Non-Muscle Invasive Bladder Cancer and HER2, sponsored by RenJi Hospital. RECRUITING as of the most recent ClinicalTrials.gov update. Talk to your doctor before contacting the trial site.

About This Trial

This is a prospective, open, single-center clinical study of anti-HER2-ADC combined with PD-1 monoclonal antibody for bladder sparing treatment in non-muscular invasive bladder cancer (NMIBC) patients with HER2-expressing. The study was conducted in accordance with the Good Clinical Practice (GCP). Approximately 20 subjects will be enrolled to evaluate the efficacy and safety of RC48 (RC48 2.0 mg/kg intravenously administered every two weeks) combined with Tislelizumab (Tislelizumab 200 mg intravenously administered every three weeks). Subjects undergo Transurethral resection of bladder tumor (TURBT), imaging diagnosis and pre-treatment biological samples of blood, urine and biopsy tissue. The study will include high-risk NMIBC patients who express HER2, fail after BCG treatment, but refuse to undergo cystectomy or do not meet the requirements for cystectomy. Subjects will receive RC48 and Tislelizumab for two years. BI-DFS were evaluated by cystoscopy, histopathologic examination, laboratory examination, and imaging examination after treatment, and tumor efficacy was evaluated when clinical studies reached the number of subjects specified in the protocol for efficacy evaluation.

What Stage of Research Is This?

Phase 2 trials evaluate whether a treatment actually works against Non-Muscle Invasive Bladder Cancer and continue monitoring side effects. Phase 2 enrolls larger groups (typically 100–300 patients) and produces the first real efficacy signal. A successful Phase 2 readout is what unlocks the much larger Phase 3 confirmatory trials needed for FDA approval.

This trial is currently recruiting participants. The sponsor has registered the study with ClinicalTrials.gov as actively enrolling, which means new applicants who meet the eligibility criteria can be considered for screening. Trial status can change between updates — confirm current recruiting status with the study contact before traveling for a screening visit.

With a target enrollment of 20 participants, this is a small study — typical of early-phase research, rare-disease trials, or pilot studies designed to generate preliminary signal before a larger study is launched.

Who May Be Eligible (Plain English)

Who May Qualify: 1. ≥18 years old 2. diagnosed by tissue sample (biopsy-confirmed) recurrent, non-muscle invasive bladder cancer; 1. Histopathology: Patients with any variant urothelial cell carcinoma (UCC) (i.e., squamous and/or glandular epithelial differentiation UCC, UCC with micropapillary changes, nest variant UCC, plasmacytoid UCC, neuroendocrine UCC, and sarcomatoid UCC) were enrolled. The presence of any lymphatic infiltration (LVI) is considered evidence of high risk. 2. Papillary carcinoma must be a high-risk disease defined as a high grade Ta/T1 lesion. In addition, subjects must have all visible tumors completely removed prior to initial administration of the study drug, as documented at baseline cystoscopy. Cytological results for high-grade urothelial carcinoma must be negative prior to initial administration of the investigational drug. 3. CIS does not require complete excision, but must be completely excised with coexisting papillary carcinoma prior to enrollment and documented at baseline cystoscopy. Negative urine cytology for malignant cells is not required. 3. When BCG recurred after treatment, the presence of HER2 expression was detected by IHC in the pathology department of our hospital 4. BCG treatment failure included no response to BCG treatment and relapse after inadequate BCG treatment ...See full criteria on ClinicalTrials.gov Always talk to your doctor about whether this trial is right for you.

These are translations of the protocol\'s inclusion and exclusion criteria, simplified for patients and caregivers. The original clinical text appears below. Eligibility is ultimately confirmed by the trial site\'s screening process — this summary is a starting point for a conversation with your doctor, not a final determination.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: 1. ≥18 years old 2. Histologically confirmed recurrent, non-muscle invasive bladder cancer; 1. Histopathology: Patients with any variant urothelial cell carcinoma (UCC) (i.e., squamous and/or glandular epithelial differentiation UCC, UCC with micropapillary changes, nest variant UCC, plasmacytoid UCC, neuroendocrine UCC, and sarcomatoid UCC) were enrolled. The presence of any lymphatic infiltration (LVI) is considered evidence of high risk. 2. Papillary carcinoma must be a high-risk disease defined as a high grade Ta/T1 lesion. In addition, subjects must have all visible tumors completely removed prior to initial administration of the study drug, as documented at baseline cystoscopy. Cytological results for high-grade urothelial carcinoma must be negative prior to initial administration of the investigational drug. 3. CIS does not require complete excision, but must be completely excised with coexisting papillary carcinoma prior to enrollment and documented at baseline cystoscopy. Negative urine cytology for malignant cells is not required. 3. When BCG recurred after treatment, the presence of HER2 expression was detected by IHC in the pathology department of our hospital 4. BCG treatment failure included no response to BCG treatment and relapse after inadequate BCG treatment 1. Subjects without response after adequate BCG treatment must meet at least one of the following criteria: 1) Persistent or recurrent simple CIS with or without recurrent Ta/T1 (non-invasive papillary carcinoma/tumor invasion of subepithelial connective tissue) disease within 12 months after completion of adequate BCG treatment; 2) Recurrent high-grade Ta/T1 disease occurred within 6 months after completion of adequate BCG treatment; 3) T1 high-grade disease was present at the first disease assessment after completion of a BCG induction course. Adequate BCG treatment (minimum treatment requirement) : at least 5 out of 6 full dose treatments were received during the initial induction course and at least 1 maintenance treatment within 6 months (one full dose per week and 2 out of 3 completed treatments); Or received at least 5 out of 6 full doses in the initial induction course and at least 2 out of 6 full doses in the second induction course. 2. Relapse after inadequate BCG treatment: Subjects must meet the following criteria: Recurrence of high-grade Ta/T1 disease within 12 months of completion of BCG treatment (as defined below): Previous inadequate BCG treatment (minimum treatment requirement) included receiving at least 5 out of 6 full dose treatments during the initial induction course. Or received at least 5 out of 6 full dose treatments during the initial induction course and at least 1 maintenance treatment (once a week and 2 out of 3 completed treatments) within 6 months. One half or one third of the dose is allowed during maintenance treatment. 5. To refuse or be unsuitable for radical cystectomy 6. ECOG 0\~1 7. The major organs are functioning normally, the following criteria are met: (1) The blood routine examination criteria should meet (no blood transfusion and no treatment with granulocyte colony stimulating factor within 14 days before enrollment) : i. Absolute count of neutrophils (ANC) ≥1,000/mm3 ii. Platelet count ≥75,000/mm3 iii. Hemoglobin ≥ 8.0g /dL (2) Liver function: i. Total bilirubin ≤1.5× prescribed ULN or direct bilirubin ≤ULN for subjects with total bilirubin levels \>1.5×ULN ii. Upper limit of normal values (ULN) ≤2.5 times of alanine Aminotransferase (ALT) and aspartate Aminotransferase (AST) Note: ≤1.5× ULN (This criterion only applies to patients who have not received anticoagulant therapy; Patients receiving anticoagulant therapy should keep anticoagulants within therapeutic limits); (3) Kidney function: The Cockcroft-Gault formula was used to determine the creatinine clearance (CrCl) \> 30 mL/min. 8\. Subjects (or their legal representatives) must sign an informed consent form (ICF) indicating that they understand the purpose and procedures of the study and are willing to participate in the study; 9. Fertile women must have a negative pregnancy test result (beta-hCG) (urine or serum) within 7 days before the study drug is first administered. Exclusion Criteria: 1. Confirmed by histology of muscular layer infiltration (T2 or higher level) bladder urothelial carcinoma. 2. Histopathological examination revealed any bladder small cell composition, pure, pure squamous cell carcinoma or simple squamous adenocarcinoma CIS; 3. Received other PD - 1 / PD - L1 inhibitor and/or HER2 inhibitor; 4. Active malignancies other than the disease being treated (i.e., disease progression within the last 24 months or requiring a change in treatment). Only the following special circumstances are allowed: i. Skin cancer that has been treated and completely cured within the last 24 months; ii. Adequately treated lobular carcinoma in situ (LCIS) and ductal CIS; iii. A history of local breast cancer and receiving antihormonal drugs or a history of local prostate cancer (N0M0) and receiving androgen blocking therapy. 5. History of uncontrolled cardiovascular disease, including: 1) any of the following in the past 3 months: unstable angina, myocardial infarction, ventricular fibrillation, toroidal ventricular tachycardia, cardiac arrest, or known congestive New York Heart Association Class III-IV heart failure, cerebrovascular accident, or transient ischemic attack; 2) Prolonged QTc interval confirmed by ECG evaluation during screening (Fridericia; QTc \> 480 ms); 3) Pulmonary embolism or other venous thromboembolism within the past 2 months. 6. Pregnancy or lactation women; 7. Known human immunodeficiency virus (HIV) infection, unless the subjects in the past six months or longer had accepted the stability of antiretroviral therapy (art), and no opportunistic infections occurred in the past 6 months, and over the past six months the CD4 count of \> 350; 8. Have evidence of active hepatitis B or hepatitis C infection (for example, a history of hepatitis C but hepatitis C virus polymerase chain reaction detection results and normal subjects of hepatitis B surface antigen antibody positive hepatitis B can groups); 9. Has yet to recover from past the toxic effects of anticancer therapy (except no clinical significance of toxic effects, such as hair loss, skin discoloration, neuropathy, and hearing impairment). 10. Wound healing delay, defined as the skin/decubitus ulcer, chronic leg ulcer, had known gastric ulcer or incision to heal. 11. 1 cycle day 1 major surgery within 4 weeks before (don't think TURBT belong to major surgery). 12. Other patients assessed by the investigator as unsuitable for participation in the study.

Treatments Being Tested

DRUG

RC48

RC48 was scheduled to be administered at a dose of 2.0mg/kg every 2 weeks, with the first dose on day 1 of the first cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.

DRUG

Tislelizumab

Tislelizumab was administered at a dose of 200 mg every 3 weeks, with the first dose on day 1 of the first 21-day cycle. The drug is diluted with normal saline and administered by intravenous drip for one hour.

Locations (1)

Trial sites listed on ClinicalTrials.gov for this study. Site activation status can vary — confirm with the specific site before traveling for a screening visit.

Ethics Committee of Shanghai Renji Hospital

Shanghai, Shanghai Municipality, China

How to Talk to Your Doctor About This Trial

Bring the printable summary of this trial — including the NCT ID (NCT05957757), the sponsor (RenJi Hospital), and the key eligibility criteria — to your next appointment. Your doctor can review the inclusion and exclusion criteria against your medical history, lab values, and current treatments to assess whether you are likely to qualify. They can also help you weigh whether trial participation makes sense alongside your existing care plan.

Useful questions to walk through together: What does the trial protocol require beyond standard care? How long is the active treatment phase, and how long is follow-up? Are there study visits at sites I can reach? Who pays for the trial-specific procedures, and who pays for standard-of-care portions? See our 25 questions to ask about clinical trials guide for a more complete checklist.

Authoritative Sources

The official record for this trial lives on ClinicalTrials.gov — the federal registry maintained by the National Library of Medicine at NIH. For background on how this trial fits into the FDA approval pathway, see the FDA drug approval process. For oncology-specific guidance for patients considering trials, the National Cancer Institute publishes patient-oriented overviews. International trial registries are aggregated by the WHO ICTRP.

Frequently Asked Questions

What is the NCT05957757 clinical trial studying?

Who can participate in NCT05957757?

Eligibility for this trial depends on the specific inclusion and exclusion criteria set by the sponsor. The plain-English summary above translates the most important criteria into accessible language; the official clinical text is preserved in the collapsible section underneath. Whether you fit any specific trial is a medical decision your doctor needs to confirm — bring the trial information to your treating physician for a full review against your medical history.

How do I contact the trial site for NCT05957757?

Contact information registered with ClinicalTrials.gov is shown in the sidebar of this page. Before reaching out, confirm with your treating physician that this trial is appropriate for your situation. The trial site will then walk you through the screening process to determine final eligibility.

Is participating in a clinical trial safe?

Clinical trials in the United States are regulated by the FDA and overseen by Institutional Review Boards (IRBs) that review the protocol for safety. Risk varies by trial — Phase 1 studies test new treatments in humans for the first time, while Phase 3 trials use treatments that have already passed earlier safety screening. The informed consent document for any specific trial details the known risks and what to expect. Discuss those risks with your physician before deciding whether to participate.

Where can I verify the data on this page?

Every detail on this page comes directly from the ClinicalTrials.gov API. Click "View on ClinicalTrials.gov" in the sidebar to see the official, unmodified record. The federal record is always authoritative; this page is a structured presentation with a plain-English eligibility translation. For background on how clinical trials are regulated, see the FDA drug approval process documentation.

How This Page Is Built

Every field on this page is pulled directly from the ClinicalTrials.gov API v2 — no estimates, no proxies. The plain-English eligibility translation is generated from the original protocol text and reviewed for fidelity to the underlying clinical criteria. The original clinical text remains visible in the collapsible section above so users and clinicians can verify the translation. Read the full methodology for the data pipeline and known limitations.

Source: ClinicalTrials.gov API v2 record for NCT05957757. Maintained by the National Library of Medicine at NIH. Public domain. Cite as: "TrialFinderData. NCT05957757. Data: ClinicalTrials.gov."

Medical disclaimer: This page is informational, not medical advice. Talk to your doctor about whether a clinical trial is right for you.

Last updated 2026-05-08 · Data from ClinicalTrials.gov.