Safety, Tolerability, and Preliminary Efficacy of KD01 Via Intravesical Instillation in Bladder Cancer (BC)

NCT07359235 | Recruiting Phase 1

• 1 other identifier: 2025-TJ-KD01T02
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

Recombinant oncolytic adenovirus injection (KD01) is an oncolytic virus product. Its main component is a conditionally replicative recombinant human type 5 adenovirus, where part of the E3 region has been replaced with the gene encoding the tBid apoptotic protein.AK104 is a humanized bispecific antibody co-targeting PD-1 (Programmed Cell Death Protein 1) and CTLA-4 (Cytotoxic T-Lymphocyte-Associated Antigen 4)-two key immune checkpoint receptors. It is designed as a novel tetrameric construct that preferentially binds to tumor-infiltrating lymphocytes (TILs) co-expressing PD-1 and CTLA-4 in the tumor microenvironment (with higher avidity than in peripheral tissues).This is a Phase I clinical study designed to evaluate the safety, tolerability, and preliminary efficacy of intravesical instillation of recombinant oncolytic adenovirus injection (KD01) in patients with bladder cancer.This study consists of Phase Ia and Phase Ib, where Phase Ia is a dose-escalation stage.The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk).The Phase Ib study will include two independent cohorts: Cohort A comprises high-risk non-muscle-invasive bladder cancer (NMIBC) patients (carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions) who have shown no response to BCG. Cohort B will include T2-4aN0-1M0 stage bladder cancer patients (clinically localized muscle-invasive bladder urothelial carcinoma).

Conditions

Bladder Cancer (BC)

Outcome Measures

Primary Outcomes (3)

• SAEs and AEs（Phase Ia）

  The incidence of serious adverse events (SAEs), the incidence and severity of adverse events (AEs).

  2 years

• MTD

  Phase Ia: The maximum tolerated dose (MTD) is determined based on the incidence of dose-limiting toxicity (DLT).

  2 years

• SAEs and AEs（Phase Ib）

  The incidence of serious adverse events (SAEs), the incidence and severity of adverse events (AEs).

  2 years

Secondary Outcomes (7)

• CRR(Phase Ia and Phase Ib Cohort A)

  24 months

• DOR（Phase Ia and Phase Ib Cohort A）

  24 months

• CRR(Phase Ib Cohort B)

  24 months

• PRR(Phase Ib Cohort B)

  24 months

• Incidence of cystectomy

  24 months

Other Outcomes (3)

• Antibodie

  2 years

• Neutralizing antibodies

  2 years

• Immunogenicity

  2 years

Study Arms (1)

KD01 treatment:

EXPERIMENTAL

Monotherapy with KD01 or combination therapy with KD01 plus AK104 for the treatment of bladder cancer.

Drug: KD01(the recombinant oncolytic adenovirus)

Interventions

KD01(the recombinant oncolytic adenovirus) DRUG

Drug： Phase Ia：KD01(3 dose groups: 2.6×10¹¹ VP, 5×10¹¹ VP, and 1×10¹² VP) Phase Ib: KD01(5×10¹¹ VP) with AK104(6 mg/kg, given intravenously every two weeks) Administration： Phase Ia: KD01 will be administered weekly during weeks 1-6, 13-15, 25-27, 37-39, 49-51, 73, 97. If patients present with CIS and/or high-grade Ta at the first efficacy assessment in week 12, KD01 will be administered weekly during weeks 16-18. Phase Ib Cohort A: KD01 for the same treatment duration as Phase Ia. AK104: The initial 6 doses will be administered, and subsequent doses will be continued based on the investigator's assessment of the patient's condition and the patient's willingness. Phase Ib Cohort B: KD01 will be administered weekly during weeks 1-6,with AK104 (3 doses). A transurethral resection of the bladder tumor (TURBT) is recommended 2-4 weeks after the final KD01 dose for residual or suspicious tumors, with subsequent treatment determined by investigators based on imaging results.

KD01 treatment:

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• The Phase Ia will include histopathologically confirmed non-muscle-invasive bladder cancer (NMIBC) patients with high-risk stratification (including extremely high-risk). High-risk stratification criteria are defined as G3/high-grade tumors that meet any of the following criteria: carcinoma in situ (CIS); stage T1; diameter\>3 cm; multiple tumors; or recurrent tumors. The Phase Ib Cohort A will include BCG unresponsive NMIBC patients with carcinoma in situ \[CIS\], with or without Ta/T1 stage lesions, while Cohort B will include histopathologically confirmed muscle-invasive bladder cancer (cT2-4aN0-1M0).Note: BCG non-response is defined as meeting any of the following criteria: 1. Persistent or recurrent CIS within 12 months after completing adequate BCG treatment; 2. Recurrence of high-grade Ta/Tl disease within 6 months after completing adequate BCG treatment; 3. High-grade T1 disease at first evaluation after induction BCG treatment. (Adequate BCG treatment is defined as: Complete at least 5 out of 6 doses in the initial induction course. plus 2 out of 6 doses from the second induction course, or 2 doses from the 3-dose maintenance course.)
• Excluding Phase Ib Cohort B, participants must either be medically ineligible for radical cystectomy as determined by urologists or have declined the procedure.
• Age 18 to 75 (including 18 and 75).
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 to 1.
• Estimated survival time is ≥2 years.6.No dysfunction of major organs, including but not limited to hematopoietic function and cardiac, pulmonary,hepatic and renal function.
• Hematologic system (no history of blood transfusion or hematopoietic growth factor treatment within 14 days)
• Absolute neutrophil count (ANC)≥1.5×109/L
• Platelets （PLT）≥75×109/L
• Hemoglobin （Hb）≥90g/L
• Hepatic function
• Total bilirubin (TBIL)≤1.5× upper limit (ULN)
• Alanine aminotransferase (ALT)≤3×ULN
• Aspartate aminotransferase (AST)≤3×ULN
• Renal function
• Creatinine （Cr）≤1.5×ULN

You may not qualify if:

• Evidence of metastatic disease, or multiple regional lymph node positivity in the true pelvis, or common iliac lymph node positivity at the screening visit. Accompanied by hydronephrosis.
• Received pelvic external beam radiation therapy within 5 years.
• Prior treatment with adenovirus-based therapies (e.g., oncolytic adenovirus, CanSino's Ad5-nCoV COVID-19 vaccine).
• Symptomatic urinary tract infection or bacterial cystitis (patients can enter the study once the treatment is satisfactory).
• Clinically significant and unexplained elevation of liver or kidney function markers.
• Women who are pregnant or breastfeeding or refuse to use contraception at any time during the study; male patients who are unwilling to use effective contraception.
• A history of malignancy in another organ system in the past 5 years, which the investigator believes may interfere with the conduct of the study or requires systemic study treatment for the malignancy.
• Patients who cannot tolerate intravesical instillation for 1 hour or bladder surgery.
• In addition to immediate postoperative instillation after TURBT , patients who have received anti-tumor treatments (including chemotherapy, radiotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, etc.) within 4 weeks before the first study drug administration must be excluded. Specifically, patients who have used nitrosourea drugs or mitomycin C within 6 weeks prior to the initial study drug administration must be excluded Patients who have used oral fluorouracil and small-molecule targeted drugs within 2 weeks prior to the first administration of the study drug or within 5 half-lives of the drugs (whichever is longer) must be excluded. Patients who have used TCMs with anti-tumor indications within 2 weeks prior to the first administration must be excluded.
• History of severe cardiovascular and cerebrovascular diseases, including but not limited to:
• Severe cardiac rhythm or conduction abnormalities, such as ventricular arrhythmias requiring clinical intervention, or second-to third-degree atrioventricular block;
• At rest, the QTcF (calculated from 12-lead ECG) is ≥460ms.
• Acute coronary syndrome, congestive heart failure, aortic dissection, stroke or other cardiovascular and cerebrovascular events of grade 3 or above occurred within 6 months before the first administration;
• Patients with NYHA class ≥II or left ventricular ejection fraction (LVEF) \<50%, or those with structural heart disease deemed high-risk by other researchers.
• Hypertension that is not clinically controlled.

Sponsors & Collaborators

• Tongji Hospital: lead

Study Sites (1)

Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, 430074, China

RECRUITING

MeSH Terms

Conditions

Urinary Bladder Neoplasms

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

Central Study Contacts

Zheng Liu, Dr.

CONTACT

+86 13297997093; lz2013tj@163.com

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: Professor

Study Record Dates

• First Submitted: January 6, 2026
• First Posted: January 22, 2026
• Study Start: November 4, 2024
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

CN (1)