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

NCT07608224 | Not Yet Recruiting Phase 2

• 1 other identifier: WCH-ZP-MIBC-RCT-01
• Study Type: interventional
• Target: 240
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Urinary Bladder Neoplasms

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Pathological Complete Response (pCR)

  At the time of radical cystectomy

• Disease-Free Survival (DFS)

  Up to 5 years after radical cystectomy

• Event-Free Survival (EFS)

  Up to 5 years after randomization

• Metastasis-Free Survival (MFS)

  Up to 5 years after randomization

• Overall Survival (OS)

  Up to 5 years after randomization

Study Arms (2)

Disitamab Vedotin + Anti-PD-1 Therapy

EXPERIMENTAL

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); Drug: Toripalimab (JS001 )

Gemcitabine and Cisplatin plus Toripalimab

ACTIVE COMPARATOR

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: Gemcitabine + Cisplatin（GC）+Toripalimab; Drug: Toripalimab (JS001 )

Interventions

Disitamab Vedotin (RC48) DRUG

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.

Disitamab Vedotin + Anti-PD-1 Therapy

Gemcitabine + Cisplatin（GC）+Toripalimab DRUG

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.

Gemcitabine and Cisplatin plus Toripalimab

Toripalimab (JS001 ) DRUG

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.

Disitamab Vedotin + Anti-PD-1 Therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Willing and able to provide written informed consent and comply with study requirements and scheduled assessments.
• Male or female patients aged ≥18 years at the time of signing informed consent.
• 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%).
• HER2 expression ≥1+ confirmed by immunohistochemistry (IHC) testing of pretreatment tumor tissue in a local laboratory.
• Deemed suitable for radical cystectomy as assessed by the investigator.
• No prior systemic chemotherapy or immunotherapy for muscle-invasive bladder cancer.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• 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
• 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.
• 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).
• Life expectancy of more than 12 months.
• Willing and able to comply with study procedures and follow-up visits.

You may not qualify if:

• 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.
• Receipt of any systemic anticancer therapy or systemic immunomodulatory agents (e.g., interferon, interleukin-2, tumor necrosis factor) within 28 days prior to enrollment.
• Prior radiotherapy for bladder cancer.
• 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.
• 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.
• 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).
• Use of traditional Chinese medicine or proprietary Chinese medicine with anti-cancer intent within 14 days prior to enrollment.
• Active autoimmune disease requiring systemic treatment that may interfere with study therapy as judged by the investigator.
• Requirement for long-term systemic corticosteroids or other immunosuppressive therapy that may interfere with study treatment.
• 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.
• 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.
• 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.
• History of immunodeficiency, including HIV infection, other acquired or congenital immunodeficiency disorders, or prior allogeneic stem cell transplantation or solid organ transplantation.
• Known hypersensitivity to any study drug, its excipients, or other monoclonal antibodies.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

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

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

disitamab vedotin; RC48 antibody; Gemcitabine; toripalimab

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Peng Zhang

CONTACT

186 0284 9307; zpeng2001@gmail.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Sub-Investigator

Study Record Dates

• First Submitted: May 18, 2026
• First Posted: May 27, 2026
• Study Start (Estimated): June 20, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): December 31, 2030
• Last Updated: May 27, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share