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

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

Interventions

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

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.

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.

Sponsors & Collaborators

• RenJi Hospital

  collaborator OTHER

• Tongji Hospital

  collaborator OTHER

• The Second Affiliated Hospital of Kunming Medical University

  collaborator OTHER

• Peking University First Hospital

  collaborator OTHER

• The First Affiliated Hospital of Air Force Medicial University

  collaborator OTHER

• The First Affiliated Hospital with Nanjing Medical University

  collaborator OTHER

• First Affiliated Hospital Xi'an Jiaotong University

  collaborator OTHER

• Tianjin Medical University Second Hospital

  collaborator OTHER

• West China Hospital

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-06-20

Primary Completion

2030-06-30

Completion

2030-12-31