Disitamab Vedotin Combined With Ivonescimab in Cisplatin-Ineligible Muscle-Invasive Bladder Cancer

NCT06957561 | Not Yet Recruiting Phase 1 DMC

• 1 other identifier: B2025-094-01
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single-arm, open-label, Phase Ib/II clinical trial designed to evaluate the efficacy and safety of Disitamab Vedotin combined with Ivonescimab in the perioperative treatment of cisplatin-ineligible patients with muscle-invasive bladder cancer (MIBC). The study will enroll MIBC patients scheduled for radical cystectomy who have not received prior immunotherapy, targeted therapy, or biological therapy, except for cisplatin chemotherapy. The trial will consist of a neoadjuvant treatment phase (Disitamab Vedotin and Ivonescimab), followed by surgery and an adjuvant treatment phase. Primary efficacy endpoints include the pathological complete response (pCR) rate, while secondary endpoints include disease-free survival, recurrence-free survival, overall survival, and clinical objective response rate. Safety will be monitored throughout the study, and biomarker testing (HER2 and PD-L1) will be conducted to assess treatment efficacy. The study aims to explore the potential of this combination therapy in improving outcomes for MIBC patients.

Conditions

Bladder Cancer; Muscle-invasive Bladder Cancer

Keywords

Cisplatin-Ineligible; Muscle-invasive bladder cancer; Disitamab Vedotin; Ivonescimab; Perioperative treatment

Outcome Measures

Primary Outcomes (1)

• Pathological Complete Response (pCR) Rate

  The percentage of patients who achieve a pathological complete response (pT0N0) after surgery following neoadjuvant treatment with Disitamab Vedotin combined with Ivonescimab.

  4 months

Secondary Outcomes (5)

• Pathological Response Rate

  4 months

• 1-3 Year Disease-Free Survival (DFS) Rate

  Up to 3 years

• Recurrence-Free Survival (RFS)

  Up to first recurrence of disease or up to 5 years

• Overall Survival (OS)

  Up to death or up to 5 years

• Clinical Objective Response Rate (ORR)

  Up to 5 years

Study Arms (1)

Disitamab Vedotin Combined with Ivonescimab

EXPERIMENTAL

Participants will receive Disitamab Vedotin (2.0 mg/kg, every 2 weeks) for 6 cycles, combined with Ivonescimab (20 mg/kg, every 3 weeks) for 4 cycles, with a total duration of 12 weeks for the neoadjuvant treatment phase. Following the completion of neoadjuvant therapy, participants will undergo radical cystectomy with pelvic lymph node dissection 4-6 weeks after the last dose. In the postoperative adjuvant phase, participants will receive Disitamab Vedotin (2.0 mg/kg, every 3 weeks, for 4 cycles) combined with Ivonescimab (20 mg/kg, every 3 weeks, for 9 cycles), starting 4-8 weeks after surgery.

Drug: Disitamab Vedotin Injection; Drug: Ivonescimab（AK112，a PD-1/VEGF bispecific antibody）; Procedure: Radical Cystectomy with Pelvic Lymph Node Dissection

Interventions

Disitamab Vedotin Injection DRUG

Participants will receive Disitamab Vedotin at a dose of 2.0 mg/kg. In the neoadjuvant phase, it will be administered every 2 weeks for 6 cycles (12 weeks total). In the postoperative adjuvant phase, it will be administered every 3 weeks for 4 cycles, starting 4-8 weeks after surgery.

Also known as: RC48-ADC

Disitamab Vedotin Combined with Ivonescimab

Ivonescimab（AK112，a PD-1/VEGF bispecific antibody） DRUG

Participants will receive Ivonescimab at a dose of 20 mg/kg. In the neoadjuvant phase, it will be administered every 3 weeks for 4 cycles (12 weeks total). In the postoperative adjuvant phase, it will be administered every 3 weeks for 9 cycles, starting 4-8 weeks after surgery.

Also known as: AK112

Disitamab Vedotin Combined with Ivonescimab

Radical Cystectomy with Pelvic Lymph Node Dissection PROCEDURE

Participants will undergo radical cystectomy with pelvic lymph node dissection 4-6 weeks after the last dose of neoadjuvant treatment.

Disitamab Vedotin Combined with Ivonescimab

Eligibility Criteria

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

You may qualify if:

• Voluntarily agree to participate in the study and sign an informed consent form.
• Male or female, aged ≥18 years.
• Expected survival ≥12 weeks.
• Pathologically confirmed muscle-invasive bladder urothelial carcinoma (MIBC), with the primary pathological component being urothelial carcinoma ≥50%, and no upper urinary tract urothelial carcinoma.
• Clinical staging (cT2-T4a, N0-1, M0) with no distant metastasis as evaluated by imaging.
• Based on urologist's assessment, the subject is able to tolerate transurethral resection and radical cystectomy.
• No prior immunotherapy, targeted therapy, or biological therapy for MIBC. Cisplatin-ineligible patients may be enrolled.
• Cisplatin chemotherapy intolerance/non-eligibility (defined as CrCl \<60 mL/min, ≥2-grade hearing impairment, ≥2-grade peripheral neuropathy, ECOG performance status of 2).
• Investigator-confirmed HER2 expression: IHC 1+, 2+, or 3+.
• ECOG performance status 0-2.
• Adequate cardiac, bone marrow, liver, and renal function, with the following parameters meeting the criteria within 7 days prior to the first dose of study drug (normal values based on the clinical trial center):
• Left ventricular ejection fraction ≥50%;
• Hemoglobin ≥9 g/dL;
• Absolute neutrophil count (ANC) ≥1.5 × 10\^9/L;
• Platelet count ≥90 × 10\^9/L;

You may not qualify if:

• Prior systemic antitumor treatment, other than cisplatin, such as targeted therapy, immunotherapy, or biological therapy, before the start of study medication.
• Major surgery within 4 weeks prior to the start of study medication.
• Positive serum virology tests (based on normal values of the study center):
• HBsAg or HBcAb positive, with positive HBV DNA copy number.
• Positive HCVAb (only if HCV RNA PCR test is negative, the subject may be eligible).
• Positive HIVAb.
• Receipt of live vaccines within 4 weeks prior to the start of study medication or plans to receive any vaccines during the study (except for the COVID-19 vaccine).
• Heart failure classified as NYHA class 3 or higher.
• Known central nervous system metastases.
• Serious arterial or venous thrombosis, or cardiovascular events such as deep vein thrombosis, pulmonary embolism, cerebral infarction, cerebral hemorrhage, myocardial infarction, etc., within 1 year before the study medication. Excluding asymptomatic lacunar infarctions that do not require clinical intervention.
• Active or progressive infections requiring systemic treatment, such as active tuberculosis.
• Systemic diseases that are not well controlled, as determined by the investigator, including diabetes, hypertension, liver cirrhosis, interstitial lung disease, obstructive lung disease, etc.
• History of serious bleeding disorders or coagulation abnormalities.
• History of gastrointestinal perforation or fistula related to anti-VEGF therapy; gastrointestinal perforation, fistula, or intra-abdominal abscess within 3 months before the first dose.
• History of esophageal or gastric varices, severe ulcers, unhealed wounds, gastrointestinal perforation, fistulas, bowel obstruction, intra-abdominal abscess, acute gastrointestinal bleeding, extensive bowel resection (partial colon resection or extensive small bowel resection with chronic diarrhea), Crohn's disease, ulcerative colitis, or long-term chronic diarrhea within 6 months before the first dose.

Sponsors & Collaborators

• Sun Yat-sen University: lead

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Urinary Bladder Neoplasms

Interventions

disitamab vedotin; Cystectomy

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)

Urologic Surgical Procedures; Urogenital Surgical Procedures; Surgical Procedures, Operative

Study Officials

• Zhuowei Liu, M.D Ph.D

  Sun Yat-sen University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zhuowei Liu, M.D Ph.D

CONTACT

+86-20-87343868; liuzhw@sysucc.org.cn

Xiangdong Li, M.D Ph.D

CONTACT

+86-20-87343840; lixiangd@sysucc.org.cn

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 26, 2025
• First Posted: May 4, 2025
• Study Start: April 30, 2025
• Primary Completion: May 1, 2026
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 4, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)