Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Urinary Bladder Neoplasms

Non-Muscle Invasive Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Tislelizumab

Disitamab vedotin

BCG Vaccine

Antineoplastic Agents, Immunological

Immunoconjugates

Immunologic Factors

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).

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.

RC48

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.

Wei Xue, Doctor

Ming Cao, Doctor

Qi Lu

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.

For Non-muscle invasive bladder cancer (NMIBC), Transurethral resection of bladder tumor (TURBT) is the primary treatment. TURBT relapses within 12 months after surgery in 10% to 67% of patients, and postoperative bladder perfusion therapy (including chemotherapy and Immunotherapy) significantly reduces the recurrence rate. However, about 30%-40% of patients will relapse after BCG treatment. Radical cystectomy is the standard of care for patients who do not respond to BCG treatment and have high grade NMIBC. However, radical cystectomy has a high incidence of postoperative complications (up to 60%) and a negative impact on HRQoL. These complications occur even in high-volume centers of excellence, whether open or minimally invasive, and the mortality rate from the surgery itself is about 3%. Therefore, some patients refuse to undergo radical cystectomy. In addition, some patients are medically unfit for surgery due to age, functional status, American Society of Anesthesiologists classification, comorbiditions, body mass index, and other factors. Although penerubicin is the only bladder sparing drug approved by the U.S. Food and Drug Administration (FDA) for patients who are not suitable for or unwilling to undergo cystectomy, BCG refractory, and with CIS NMIBC, no legally marketed penerubicin drug is available in China. Therefore, new treatments are needed to prevent invasive bladder cancer from affecting the entire bladder.

In recent years, immunocheckpoint inhibitors represented by PD-1/PD-L1 have been proved to be a promising means of tumor immunotherapy, which has made a breakthrough in the treatment of advanced urothelial carcinoma, and become the main choice for the treatment of advanced urothelial carcinoma. Immunocheckpoint inhibitors also showed positive results in patients who did not respond to BCG treatment during perioperative and perioperative periods.Therefore, immunotherapy is expected to be an alternative bladder sparing therapy for high-risk NMIBC patients.The anti-HER2-ADC drug RC48 also achieved significant efficacy in HER2-overexpressed advanced urothelial carcinoma, and its combination with PD-1 monoclonal antibody Toripalimab was more effective in the first-line treatment of advanced metastatic urothelial carcinoma. Therefore, RC48 combined with PD-1 can be used as a potential treatment for bladder sparing in patients with NMIBC.

In NMIBC patients with HER2 expression, ADC drugs can target tumor cells and deliver cytotoxic drugs with greater safety than chemotherapy. In addition, the application of anti-HER2-ADC drugs combined with PD-1 in bladder sparing therapy is still lacking in experience and related studies. Therefore, we plan to conduct a study on bladder preservation therapy for patients with HER2-expressing NMIBC treated with ADC drugs combined with PD-1 monoclonal antibody, so as to preserve the bladder function of patients while controlling tumor recurrence and ensuring their quality of life.

To study the safety and efficacy of RC48 combined with Tislelizumab in HER2 expression high grade non muscle invasive bladder cancer patients who failed BCG therapy and refused cystectomy.

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

Defined by time from enrollment to the occurrence of one of the following events: first MIBC or regional lymph node recurrence, distant metastasis, or death

Defined by time from day of first treatment to first progression to higher grade or stage, including muscle-invasive disease or death from any cause.

Defined by time from day of first treatment to first deterioration

Defined by time from day of first treatment to radical cystectomy

Defined by time from day of first treatment to invasive bladder cancer

Defined by time from day of first treatment to death

CR is defined by negative cystoscopy, urine cytology, and bladder biopsies.

Defined by time from day of first treatment to recurrent NMIBC based on cystoscopy, cytology and/or biopsy.

RemeGen Co., Ltd.

BeiGene

RenJi Hospital

Rare Diseases

Carcinoma, Transitional Cell

Transitional Cell Carcinoma

Docetaxel

Tubulin Modulators

Antimitotic Agents

Subjects will be enrolled in sequential, dose escalating cohorts of NanoDoce direct injection (0.75, 1.5, 2.5, or 3.75 mg/mL). Subjects will also receive an initial NanoDoce intravesical instillation at 2.0 or 3.0 mg/mL and additional Induction (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and Maintenance (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest) instillations at 2.0 or 3.0 mg/mL.

Subjects will be enrolled in sequential, dose escalating cohorts of NanoDoce direct injection (0.75, 1.5, 2.5, or 3.75 mg/mL). Subjects will also receive an initial NanoDoce intravesical instillation at 2.0 or 3.0 mg/mL. Subjects will then go on to receive institutional standard of care.

Subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT)

NanoDoce (direct injection)

All subjects will receive an initial intravesical instillation within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Visit 2 Instillation

Group 2 (MIBC) will receive institutional standard of care treatments after the Visit 2 intravesical instillation.

Institutional Standard of Care

Group 1 (NMIBC) will receive intravesical instillations in an Induction Period and a Maintenance Period.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations

Donald Lamm, MD, FACS

This is a clinical trial studying the administration of NanoDoce as a direct injection to the bladder wall immediately after tumor resection and as an intravesical instillation. All participants will receive NanoDoce, and will be evaluated for safety and tolerability, as well as the potential effects of NanoDoce on urothelial carcinoma.

In this clinical trial, subjects with high-risk non-muscle invasive bladder cancer (NMIBC) or muscle invasive bladder cancer (MIBC), will receive NanoDoce. Subjects will be stratified into two treatment groups, Group 1 (NMIBC) and Group 2 (MIBC). All subjects will receive NanoDoce injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT), followed by an initial NanoDoce intravesical instillation.

Once the TURBT resection site is healed (approximately 1 month), Group 1 (NMIBC) subjects will proceed to a 3-month Induction period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest). After the Induction period, following confirmation of non-recurrence, Group 1 subjects will proceed to a 3-month Maintenance period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest).

After NanoDoce direct injection and the initial intravesical instillation, Group 2 subjects will proceed to institutional standard of care and will not receive Induction or Maintenance intravesical instillations.

Open-label, dose rising trial consisting of a dose escalation phase and a dose confirmation phase for direct injection doses. In the dose escalation phase, subjects will be enrolled in sequential cohorts of three subjects starting at the lowest concentration. The dose determined to be most suitable for further evaluation will enroll additional subjects to total up to 12 subjects at that dose level.

The study will also dose escalate Groups 1 and 2 for the intravesical instillation of NanoDoce concentrations (2.0 and 3.0 mg/mL).

Evaluation of NanoDoce® in Participants With Urothelial Carcinoma

Phase 1/2 Trial Evaluating the Safety and Tolerability of NanoDoce® Injection and Intravesical Instillation in Subjects With Urothelial Carcinoma

Treatment Emergent Adverse Events included laboratory assessments, physical examination findings, and vital signs.

No evidence of tumor recurrence or disease progression

Disease progression at Day 45 derived from cytology and biopsy assessments

US Biotest, Inc.

NanOlogy, LLC

Subjects were required to spontaneously report any AEs. Study personnel asked open-ended questions to obtain information about AEs at every visit.

NanoDoce (direct injection): Subjects received NanoDoce 0.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 0.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 1.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 1.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period Maintenance (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 2.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 or 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period Maintenance (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Non-Muscle Invasive Bladder Cancer (Group 1) 3.75 mg/mL

NanoDoce (direct injection): Subject received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subject received an initial intravesical instillation of NanoDoce at 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subject received intravesical instillations of NanoDoce at 3.0 mg/mL in an Induction Period (6 weekly NanoDoce intravesical instillations, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) Subset 3.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 0.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 0.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 1.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 1.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 2.5 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation): Subjects received an initial intravesical instillation of NanoDoce 3.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Muscle Invasive Bladder Cancer (Group 2) 3.75 mg/mL

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 mg/mL or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an initial intravesical instillation of NanoDoce at 2.0 or 3.0 mg/mL within 2 hours of direct injection.

NanoDoce (intravesical instillation) - Induction and Maintenance Instillations: Subjects received intravesical instillations of NanoDoce in an Induction Period (6 weekly NanoDoce intravesical instillations at 2.0 or 3.0 mg/mL, followed by 6 weeks of rest) and a Maintenance Period (3 weekly NanoDoce intravesical instillations at 3.0 mg/mL, followed by 9 weeks of rest). Total dose administered for intravesical instillations could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL or 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 2.5 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 2.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 50 mg in 25 mL of saline for a final concentration of 2.0 mg/mL.

NanoDoce (direct injection): Subjects received NanoDoce 3.75 mg/mL (up to 4 mL) injected into the index tumor resection site on the bladder wall, immediately following transurethral resection of the bladder tumor (TURBT).

NanoDoce (intravesical instillation) - Subjects received an intravesical instillation of NanoDoce 3.0 mg/mL within 2 hours of direct injection. Total dose administered for intravesical instillation could not exceed 75 mg in 25 mL of saline for a final concentration of 3.0 mg/mL.

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Dr. Gere diZerega

Incidence of Treatment Emergent Adverse Events (Safety and Tolerability)

Non-Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort

Non-Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort

All subjects from the NMIBC Group 1 were evaluated for RFS. No subjects in the MIBC Group 2 or MIBC Group 2 Subset were evaluated for RFS.

Recurrence Free Survival (RFS)

Muscle Invasive Bladder Cancer - 0.75 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 1.5 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 2.5 mg/mL NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer - 3.75 NanoDoce Injection Cohort

Muscle Invasive Bladder Cancer Subset (Group 2 Subset) - 3.75/mg/mL NanoDoce Injection

The muscle invasive bladder cancer (MIBC) (Group 2) and MIBC Group 2 Subset were assessed for disease progression at Day 45. There were two subjects in the 3.75 mg/mL NanoDoce cohort for whom disease status at Day 45 was unknown, and there were two subjects withdrawn from the study prior to analysis of disease progression at Day 45.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
RC48 Combined With Tislelizumab for Bladder Sparing Treatment in NMIBC With BCG Treatment Failure and HER2 Expression	NCT05957757	Non-Muscle Inva... HER2	RC48 Tislelizumab	18 Years -	RenJi Hospital
Evaluation of NanoDoce® in Participants With Urothelial Carcinoma	NCT03636256	Bladder Cancer Urothelial Carc... Urinary Bladder... Urinary Bladder... Urogenital Neop... Urologic Neopla... Urologic Cancer Malignant Tumor... Cancer of the B...	NanoDoce (direc... NanoDoce (intra... Institutional S... NanoDoce (intra...	18 Years -	NanOlogy, LLC
RC48 Combined With Tislelizumab for Bladder Sparing Treatment in NMIBC With BCG Treatment Failure and HER2 Expression	NCT05957757	Non-Muscle Inva... HER2	RC48 Tislelizumab	18 Years -	RenJi Hospital

Spots Global Cancer Trial Database for bcg failure

Every month we try and update this database with for bcg failure cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for bcg failure

Every month we try and update this database with for bcg failure cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for bcg failure cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.