HOPE-07-MIBC: Disitamab Vedotin Plus Immunotherapy vs Chemoimmunotherapy in Resectable HER2-Expressing MIBC (HOPE-07-MIBC)

A Prospective, Randomized Controlled Study of Perioperative Disitamab Vedotin Plus Immunotherapy Versus Chemotherapy Plus Immunotherapy in Patients With Resectable HER2-Expressing Muscle-Invasive Bladder Cancer (HOPE-07-MIBC Study)

This is a multicenter, randomized controlled clinical trial (HOPE-07) designed to evaluate the efficacy and safety of perioperative treatment with disitamab vedotin (RC48) combined with toripalimab compared with toripalimab combined with chemotherapy in patients with resectable HER2-expressing (HER2 1+, 2+, or 3+) muscle-invasive bladder cancer (MIBC, cT2-4aN0/1M0).A total of 240 patients will be enrolled and randomized in a 1:1 ratio to receive either RC48 plus toripalimab or chemotherapy plus toripalimab, with 120 patients in each arm.

The primary objective is to compare 2-year event-free survival (2-year EFS) between the two treatment groups.

Secondary endpoints include pathological complete response (pCR), event-free survival (EFS), disease-free survival (DFS), 1-year event-free survival (1-year EFS), metastasis-free survival (MFS), overall survival (OS), R0 resection rate, and safety outcomes including adverse events (AEs), serious adverse events (SAEs), vital signs, physical examination, ECOG performance status, laboratory tests, and electrocardiography, assessed according to CTCAE v5.0.

Exploratory objectives include assessment of quality of life using EQ-5D-5L and EORTC QLQ-C30, evaluation of associations between biomarkers (HER2 expression, PD-L1 expression, circulating tumor DNA) and treatment efficacy, and multi-omics analyses using tumor tissue, ctDNA, and urinary tumor DNA to identify potential predictive biomarkers.

Study Overview

• Status: Not yet recruiting
• Conditions: Urinary Bladder Neoplasms
• Intervention / Treatment: Drug: Disitamab Vedotin (RC48); Drug: Toripalimab (JS001 ); Drug: Toripalimab (JS001 ); Drug: Gemcitabine + Cisplatin（GC）+Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 240
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Peng Zhang; Phone Number: 186 0284 9307; Email: zpeng2001@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Willing and able to provide written informed consent and comply with study requirements and scheduled assessments.
2. Male or female patients aged ≥18 years at the time of signing informed consent.
3. Histologically or radiologically confirmed muscle-invasive bladder cancer (MIBC) staged as cT2-T4aN0/1M0 according to AJCC 8th edition, with residual disease after transurethral resection of bladder tumor (TURBT) as assessed by the investigator. All patients must have histological evidence of muscularis propria invasion. For mixed histology tumors, urothelial carcinoma must be the predominant component (≥50%).
4. HER2 expression ≥1+ confirmed by immunohistochemistry (IHC) testing of pretreatment tumor tissue in a local laboratory.
5. Deemed suitable for radical cystectomy as assessed by the investigator.
6. No prior systemic chemotherapy or immunotherapy for muscle-invasive bladder cancer.
7. Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.

8. Adequate organ function as defined by the following laboratory criteria obtained within 14 days prior to enrollment (unless otherwise specified):

   Absolute neutrophil count (ANC) ≥1.5 × 10⁹/L Platelet count ≥100 × 10⁹/L Hemoglobin ≥90 g/L International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 × upper limit of normal (ULN) Total bilirubin ≤1.5 × ULN AST, ALT, and alkaline phosphatase ≤2.5 × ULN Creatinine clearance (CrCl) >40 mL/min Left ventricular ejection fraction (LVEF) ≥50% For borderline renal function: CrCl ≥40 to <60 mL/min (defined subgroup); adequate renal function: CrCl ≥60 mL/min

9. Women of childbearing potential must agree to use highly effective contraception during the study and for at least 180 days after the last dose of disitamab vedotin or toripalimab (whichever occurs later). A negative urine or serum pregnancy test is required within 7 days prior to enrollment.
10. Non-sterilized male patients must agree to use highly effective contraception during the study and for at least 180 days after the last dose of disitamab vedotin or toripalimab (whichever occurs later).
11. Life expectancy of more than 12 months.
12. Willing and able to comply with study procedures and follow-up visits.

Exclusion Criteria:

1. Prior treatment with therapies targeting PD-1, PD-L1, PD-L2, CTLA-4, HER2, or any other immune checkpoint or T-cell co-stimulatory pathways.
2. Receipt of any systemic anticancer therapy or systemic immunomodulatory agents (e.g., interferon, interleukin-2, tumor necrosis factor) within 28 days prior to enrollment.
3. Prior radiotherapy for bladder cancer.
4. Prior systemic antitumor therapy for bladder cancer (e.g., chemotherapy), except for intravesical chemotherapy or immunotherapy completed at least 2 weeks prior to initiation of study treatment.
5. Major surgery or significant traumatic injury within 28 days prior to enrollment. Placement of vascular access devices and transurethral resection of bladder tumor (TURBT) are not considered major surgery.
6. Severe infections requiring systemic antibacterial, antifungal, or antiviral therapy within 14 days prior to enrollment (hepatitis B virus infection is addressed in exclusion criterion 12).
7. Receipt of live vaccines within 28 days prior to enrollment (inactivated influenza vaccines are allowed; intranasal vaccines are considered live vaccines and are not allowed).
8. Use of traditional Chinese medicine or proprietary Chinese medicine with anti-cancer intent within 14 days prior to enrollment.
9. Active autoimmune disease requiring systemic treatment that may interfere with study therapy as judged by the investigator.
10. Requirement for long-term systemic corticosteroids or other immunosuppressive therapy that may interfere with study treatment.
11. Any uncontrolled comorbid conditions that may affect study participation, including but not limited to significant electrolyte abnormalities, hypoalbuminemia, interstitial lung disease, non-infectious pneumonitis, uncontrolled tuberculosis, neurological disorders, psychiatric disorders, or uncontrolled systemic diseases. This includes uncontrolled cardiovascular disease such as active cardiac disease within 6 months prior to enrollment, including severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, or clinically significant arrhythmias requiring treatment.
12. Chronic hepatitis B infection with HBV DNA ≥500 IU/mL (2500 copies/mL) without adequate antiviral therapy. Patients with inactive HBsAg carrier status or well-controlled HBV infection (HBV DNA <500 IU/mL under antiviral therapy) may be eligible. HBV DNA testing is required only in HBsAg-positive patients.
13. Active hepatitis C infection. Patients who are HCV antibody negative, or HCV antibody positive with negative HCV RNA, are eligible. HCV RNA testing is required for HCV antibody-positive patients.
14. History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency disorders, or prior allogeneic stem cell transplantation or solid organ transplantation.
15. Known hypersensitivity to any study drug, its excipients, or other monoclonal antibodies.
16. Pregnant or breastfeeding women.
17. Concurrent participation in another interventional clinical trial.
18. Presence of another active malignancy, except for adequately treated non-melanoma skin cancer or other malignancies considered cured.
19. Any condition that, in the investigator's judgment, makes the patient unsuitable for participation in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Disitamab Vedotin + Anti-PD-1 Therapy; Patients in the experimental arm will receive perioperative treatment with disitamab vedotin (RC48) in combination with toripalimab. The treatment includes a neoadjuvant phase of 6 cycles of RC48 plus toripalimab, followed by radical cystectomy. After surgery, patients will receive 6 cycles of adjuvant therapy with RC48 plus toripalimab. Toripalimab maintenance therapy will be continued for up to 1 year in patients without disease progression or unacceptable toxicity.	Drug: Disitamab Vedotin (RC48); Disitamab vedotin (RC48) will be administered in combination with toripalimab in the experimental arm. Treatment consists of 6 cycles in the neoadjuvant setting prior to radical cystectomy, followed by 6 cycles in the adjuvant setting after surgery. Toripalimab maintenance therapy will continue for up to 1 year in patients without disease progression or unacceptable toxicity.; Drug: Toripalimab (JS001 ); Toripalimab will be administered in combination with disitamab vedotin in the experimental arm during both neoadjuvant and adjuvant phases, and will be continued as maintenance therapy for up to 1 year after surgery in patients without disease progression or unacceptable toxicity.; Drug: Toripalimab (JS001 ); Toripalimab will be administered in combination with GC chemotherapy in the neoadjuvant setting for 4 cycles prior to radical cystectomy and will be continued as maintenance therapy for up to 1 year after surgery in patients without disease progression or unacceptable toxicity.
Active Comparator: Gemcitabine and Cisplatin plus Toripalimab; Patients in the control arm will receive perioperative treatment with gemcitabine and cisplatin (GC) chemotherapy in combination with toripalimab. The treatment includes a neoadjuvant phase of 4 cycles of GC chemotherapy plus toripalimab, followed by radical cystectomy. After surgery, patients will receive toripalimab maintenance therapy for up to 1 year in patients without disease progression or unacceptable toxicity.	Drug: Toripalimab (JS001 ); Toripalimab will be administered in combination with disitamab vedotin in the experimental arm during both neoadjuvant and adjuvant phases, and will be continued as maintenance therapy for up to 1 year after surgery in patients without disease progression or unacceptable toxicity.; Drug: Toripalimab (JS001 ); Toripalimab will be administered in combination with GC chemotherapy in the neoadjuvant setting for 4 cycles prior to radical cystectomy and will be continued as maintenance therapy for up to 1 year after surgery in patients without disease progression or unacceptable toxicity.; Drug: Gemcitabine + Cisplatin（GC）+Toripalimab; Gemcitabine and cisplatin (GC) chemotherapy will be administered in combination with toripalimab in the control arm. Treatment consists of 4 cycles in the neoadjuvant setting prior to radical cystectomy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
2-year Event-Free Survival	Event-free survival is defined as the time from randomization to disease progression, recurrence, metastasis, or death from any cause, whichever occurs firsth	From randomization to 2 years after treatment initiation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Complete Response (pCR)	Pathological complete response is defined as the absence of residual viable tumor cells in the surgical specimen (ypT0N0) at radical cystectomy.	At the time of radical cystectomy
Disease-Free Survival (DFS)	Disease-free survival is defined as the time from radical cystectomy to tumor recurrence or death from any cause, whichever occurs first.	Up to 5 years after radical cystectomy
Event-Free Survival (EFS)	Event-free survival is defined as the time from randomization to disease progression, recurrence, metastasis, or death from any cause, whichever occurs first.	Up to 5 years after randomization
Metastasis-Free Survival (MFS)	Metastasis-free survival is defined as the time from randomization to distant metastasis or death from any cause.	Up to 5 years after randomization
Overall Survival (OS)	From the date of randomization until death from any cause, assessed up to 5 years	Up to 5 years after randomization
R0 Resection Rate	R0 resection rate is defined as the proportion of patients achieving microscopically margin-negative resection at radical cystectomy.	At the time of radical cystectomy
Incidence of Adverse Events	Safety will be assessed by incidence and severity of adverse events and serious adverse events, graded according to CTCAE version 5.0. Assessments include vital signs, physical examination, ECOG performance status, laboratory tests, and electrocardiography.	From first dose until 30 days after last dose (or up to 1 year follow-up)

Collaborators and Investigators

• Sponsor: West China Hospital
• Collaborators: The First Affiliated Hospital with Nanjing Medical University; Peking University First Hospital; RenJi Hospital; Tongji Hospital; First Affiliated Hospital Xi'an Jiaotong University; Tianjin Medical University Second Hospital; The Second Affiliated Hospital of Kunming Medical University; The First Affiliated Hospital of Air Force Medicial University

Study record dates

Study Major Dates

• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 18, 2026
• First Submitted That Met QC Criteria: May 24, 2026
• First Posted (Actual): May 27, 2026

Study Record Updates

• Last Update Posted (Actual): May 27, 2026
• Last Update Submitted That Met QC Criteria: May 24, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Male Urogenital Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urologic Neoplasms; Urinary Bladder Diseases; Urinary Bladder Neoplasms; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Gemcitabine; disitamab vedotin; toripalimab; RC48 antibody
• Other Study ID Numbers: WCH-ZP-MIBC-RCT-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No