DV Plus Toripalimab With Cetirizine and Mecobalamin Pretreatment in Patients With Locally Advanced Unresectable or Metastatic Bladder Cancer

NCT07853053 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: SYSKY-2026-733-01
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This is a prospective, open-label, single-arm exploratory clinical study evaluating the efficacy and safety of disitamab vedotin (RC48) plus toripalimab with cetirizine and mecobalamin in patients with locally advanced unresectable or metastatic bladder cancer who have not received prior systemic therapy for advanced disease. Disitamab vedotin is a HER2-targeted antibody-drug conjugate, and toripalimab is a PD-1 immune checkpoint inhibitor. Although antibody-drug conjugates have shown antitumor activity in urothelial cancer, treatment-related peripheral neuropathy may affect patients' quality of life and the ability to continue treatment. In this study, cetirizine and mecobalamin are incorporated as a supportive and preventive strategy to explore whether they may help reduce or delay treatment-related peripheral neuropathy while maintaining antitumor activity. Approximately 10 to 20 participants will be enrolled. The primary outcomes are objective response rate according to RECIST v1.1 and the incidence of treatment-related Grade 2 or higher peripheral neuropathy. Secondary outcomes include overall safety, disease control rate, progression-free survival, and overall survival. Exploratory analyses will evaluate changes in the tumor immune microenvironment, including CD8-positive T-cell infiltration and activation, and their associations with treatment response and peripheral neuropathy.

Conditions

Bladder Cancer

Keywords

Disitamab Vedotin; Toripalimab; Cetirizine; Mecobalamin; ADC-related Peripheral Neuropathy

Outcome Measures

Primary Outcomes (2)

• Objective Response Rate (ORR)

  The proportion of efficacy-evaluable participants whose best overall response is complete response (CR) or partial response (PR), as assessed according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. ORR is calculated as the number of participants with CR or PR divided by the total number of efficacy-evaluable participants.

  From baseline until disease progression, death, initiation of new anticancer therapy, withdrawal of consent, loss to follow-up, or study completion; assessed every 4 weeks (±7 days).

• Incidence of Treatment-Related Grade 2 or Higher Peripheral Neuropathy

  The proportion of participants in the safety analysis population who develop treatment-related Grade 2 or higher peripheral neuropathy during study treatment. Peripheral neuropathy will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0 and may include peripheral sensory neuropathy, peripheral motor neuropathy, paresthesia, numbness, tingling, pain, burning sensation, hypoesthesia, muscle weakness, impaired fine motor function, or gait instability. Events will be considered treatment-related based on investigator assessment.

  From the first dose of study treatment through the end of study treatment.

Secondary Outcomes (4)

• Incidence of Adverse Events and Serious Adverse Events

  From the first dose through the protocol-defined safety follow-up period; routine safety assessments through 28 days after the last dose, with SAE monitoring through 90 days after the last dose.

• Disease Control Rate (DCR)

  From baseline until disease progression, death, initiation of new anticancer therapy, withdrawal of consent, loss to follow-up, or study completion; assessed every 4 weeks (±7 days).

• Progression-Free Survival (PFS)

  From the first administration of study treatment until documented disease progression or death from any cause, whichever occurs first, through study completion.

• Overall Survival (OS)

  From the first administration of study treatment until death from any cause, through study completion.

Other Outcomes (1)

• Changes in Tumor, Neuroinflammatory, and Immune Biomarkers

  Baseline and during or after study treatment, through study completion.

Study Arms (1)

Disitamab Vedotin Plus Toripalimab With Cetirizine and Mecobalamin

EXPERIMENTAL

Participants will receive disitamab vedotin 2.0 mg/kg intravenously every 2 weeks and toripalimab 240 mg intravenously every 3 weeks, together with cetirizine 10 mg orally once daily and mecobalamin 0.5 mg orally three times daily. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of a new anticancer therapy, completion of protocol-specified treatment where applicable, or investigator decision. Cetirizine and mecobalamin are administered as a prophylactic/supportive strategy to explore their potential effects on treatment-related peripheral neuropathy and antitumor immune responses.

Drug: Disitamab Vedotin; Drug: Toripalimab; Drug: Cetirizine; Drug: Mecobalamin

Interventions

Disitamab Vedotin DRUG

Disitamab vedotin will be administered intravenously at 2.0 mg/kg every 2 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of a new anticancer therapy, or investigator decision to discontinue treatment.

Disitamab Vedotin Plus Toripalimab With Cetirizine and Mecobalamin

Toripalimab DRUG

Toripalimab will be administered intravenously at 240 mg every 3 weeks. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of a new anticancer therapy, completion of protocol-specified treatment, or investigator decision to discontinue treatment.

Disitamab Vedotin Plus Toripalimab With Cetirizine and Mecobalamin

Cetirizine DRUG

Cetirizine will be administered orally at 10 mg once daily during study treatment as a prophylactic/supportive intervention to explore its potential effects on treatment-related peripheral neuropathy and antitumor immune responses. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of a new anticancer therapy, or investigator decision to discontinue treatment.

Disitamab Vedotin Plus Toripalimab With Cetirizine and Mecobalamin

Mecobalamin DRUG

Mecobalamin will be administered orally at 0.5 mg three times daily during study treatment as a prophylactic/supportive intervention to explore its potential effects on treatment-related peripheral neuropathy. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, initiation of a new anticancer therapy, or investigator decision to discontinue treatment.

Disitamab Vedotin Plus Toripalimab With Cetirizine and Mecobalamin

Eligibility Criteria

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

You may qualify if:

• Voluntarily agrees to participate in the study, is able to provide written informed consent, and is able to understand and comply with the study requirements and assessment schedule.
• Age ≥18 years, regardless of sex.
• Histologically or cytologically confirmed bladder urothelial carcinoma, including pure urothelial carcinoma or mixed bladder carcinoma with a predominant urothelial carcinoma component (≥50%), with clinically diagnosed unresectable locally advanced, recurrent, or metastatic disease that is not suitable for curative surgery or definitive radiotherapy.
• HER2 expression ≥1+ by immunohistochemistry, as determined at the local laboratory using a pretreatment tumor specimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ function, as demonstrated by the following laboratory values obtained within 14 days before enrollment:
• a. The following hematologic criteria must be met without growth factor support within 14 days before sample collection: i. Absolute neutrophil count ≥1.5 × 10\^9/L; ii. Platelet count ≥90 × 10\^9/L; iii. Hemoglobin ≥90 g/L. b. International normalized ratio (INR) or activated partial thromboplastin time (aPTT) ≤1.5 × the upper limit of normal (ULN).
• c. Total serum bilirubin ≤1.5 × ULN; for participants with Gilbert syndrome or predominantly indirect hyperbilirubinemia of extrahepatic origin, total bilirubin must be ≤3 × ULN.
• d. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase ≤2.5 × ULN.
• At least one measurable lesion according to RECIST version 1.1.
• Any adverse events related to prior anticancer treatment must have recovered to Grade 0 or 1 before enrollment, except for clinically insignificant toxicities such as alopecia, pigmentation changes, or stable endocrine abnormalities controlled with replacement therapy.
• No peripheral neuropathy at enrollment. Participants with a history of peripheral neuropathy must have Grade 0 peripheral neuropathy at enrollment.
• Female participants of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during study treatment and for the protocol-specified period after the last dose. Male participants with partners of childbearing potential must also agree to use effective contraception.

You may not qualify if:

• Prior systemic anticancer treatment for advanced, recurrent, or metastatic bladder cancer, including chemotherapy, immunotherapy, targeted therapy, antibody-drug conjugates (ADCs), or other investigational anticancer agents.
• Prior treatment with disitamab vedotin, another HER2-targeted ADC, or an MMAE-containing ADC; or a history of severe immune-related adverse events associated with prior treatment with PD-1, PD-L1, CTLA-4, or other immune checkpoint inhibitors.
• Known hypersensitivity to disitamab vedotin, toripalimab, cetirizine, mecobalamin, or any component of these agents.
• Grade 2 or higher peripheral neuropathy, or a severe neurologic disorder that, in the investigator's judgment, may interfere with assessment of neurotoxicity, including but not limited to severe diabetic peripheral neuropathy, spinal cord compression, severe spinal canal stenosis, active neuritis, or demyelinating disease.
• Active or previously diagnosed autoimmune disease that may worsen with PD-1 inhibitor therapy, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, systemic sclerosis, vasculitis, autoimmune hepatitis, or multiple sclerosis.
• Receipt of a live vaccine within 28 days before enrollment. Seasonal injectable influenza vaccines that are inactivated are permitted; intranasal live vaccines are not permitted.
• Active central nervous system metastases, leptomeningeal metastases, or carcinomatous meningitis. Participants with previously treated brain metastases may be considered eligible if the lesions are stable, the participant is asymptomatic, corticosteroids have been discontinued or reduced to a low dose, and enrollment is considered safe by the investigator.
• Requirement for long-term high-dose corticosteroid therapy or other immunosuppressive therapy that, in the investigator's judgment, may interfere with study treatment.
• Clinically significant abnormalities of potassium, sodium, or calcium; hypoalbuminemia; interstitial lung disease; noninfectious pneumonitis; or other uncontrolled systemic diseases that, in the investigator's judgment, may interfere with study treatment, including uncontrolled diabetes mellitus, hypertension, or cardiovascular disease. This includes active cardiac disease within 6 months before enrollment, such as severe or unstable angina, myocardial infarction, symptomatic congestive heart failure, or ventricular arrhythmias requiring medical treatment.
• Untreated chronic hepatitis B infection or hepatitis B virus (HBV) carrier status with HBV DNA ≥500 IU/mL (2500 copies/mL). Participants who are inactive hepatitis B surface antigen carriers or who have stable active HBV infection after continuous antiviral therapy with HBV DNA \<500 IU/mL may be enrolled. HBV DNA testing is required only for participants who are positive for hepatitis B core antibody.
• Active hepatitis C infection. Participants with a negative hepatitis C virus (HCV) antibody test during screening, or those with a positive HCV antibody test but negative HCV RNA, may be enrolled. Participants with a positive HCV antibody test must undergo HCV RNA testing.
• History of immunodeficiency, including positive human immunodeficiency virus (HIV) testing or other acquired or congenital immunodeficiency disorders, or a history of allogeneic stem cell transplantation or organ transplantation.
• Major surgery, definitive radiotherapy, or extensive palliative radiotherapy within 4 weeks before enrollment, or unresolved surgery- or radiotherapy-related toxicity above Grade 1.
• Another malignancy within the previous 5 years, except for malignancies that have been definitively treated and are considered to have a low risk of recurrence, such as basal cell carcinoma of the skin, squamous cell carcinoma of the skin, cervical carcinoma in situ, low-risk prostate cancer, or adequately treated non-muscle-invasive bladder cancer.
• Pregnant or breastfeeding women.

Sponsors & Collaborators

• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: lead

Study Sites (1)

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, Guangdong, 510000, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

disitamab vedotin; toripalimab; Cetirizine; mecobalamin

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)

Hydroxyzine; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, open-label, single-arm, exploratory interventional study using a Bayesian adaptive design. All enrolled participants will receive disitamab vedotin plus toripalimab with cetirizine and mecobalamin. The study plans to enroll 10 to 20 participants. Interim analyses will be conducted after 10, 12, 14, 16, and 18 evaluable participants, with a maximum sample size of 20, to dynamically assess both antitumor efficacy and treatment-related peripheral neuropathy.

Study Record Dates

• First Submitted: September 27, 2026
• First Posted: October 1, 2026
• Study Start (Estimated): January 1, 2027
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: October 1, 2026

Record last verified: 2026-09

Locations

CN (1)