An Open-Label, International, Multicenter Phase II Study to Evaluate the Efficacy and Safety of Intravesical T3011 Injection in Participants With BCG-Unresponsive High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC) or BCG-Exposed, Chemotherapy-Unresponsive Intermediate /High-Risk NMIBC

Study Identifier:
MVR-T3011-006
CT.gov Identifier:
NCT06971614
EudraCT Identifier:
N/A
EU Trial (CTIS) Number:
N/A
Study Contact Information:
(210) 593-5651 or [email protected]
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Study Summary

This is a single-arm, open-label, multicenter, phase II clinical study to evaluate the tolerability, safety, and preliminary efficacy of intravesical administration of Herpes Virus T3011 Injection in participants with BCG-unresponsive high risk non-muscle-invasive bladder cancer (NMIBC) . To confirm the recommended Phase II dose (Recommended Phase II Dose) based on the existing 2×10 9 PFU dose, and to expand the evaluation of the drug's anti-tumor efficacy in patients with BCG-unresponsive non-muscle invasive bladder cancer based on the optimized dose. To evaluate clinical efficacy indicators including complete response rate (Complete Response Rate), event-free survival rate (Event-free Survival Rate) and recurrence-free survival rate (Recurrence-free Survival Rate), and to evaluate safety data and pharmacokinetic parameters

To assess the efficacy and safety of intravesical T3011 in BCG‑naïve high‑risk NMIBC patients.

Patients will be evaluated for recurrence and progression using cystoscopy, cytology, biopsy (if applicable), and CT/MRI (if applicable).

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Bladder
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    II
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
    N/A
    Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    Inclusion criteria
    • Participants may enter the study only if they meet all the following criteria:
    • Male or female, aged ≥18 years at the time of signing the ICF.
    • The participants will need to meet the following criteria:
    • Participants with a histologically confirmed diagnosis of NMIBC (Ta, T1 and/or Cis).
    • During the study, the participants must voluntarily comply with the study-specified cystoscopy, urine cytology and randomized biopsy.
    • All toxicities caused by prior radiotherapy, chemotherapy or other treatments have recovered to Grade ≤1 (CTCAE 5.0) (except for alopecia), including but not limited to urinary tract infection, urinary tract irritation, and macroscopic hematuria; participants with Grade >1 anti-neoplastic treatment-related toxicities during the screening period may be enrolled after discussion of the investigators and the sponsor.
    • Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2.
    • Expected survival ≥24 weeks.
    • Laboratory test values meeting the following requirements :
    • Hematology ANC≥1.5×10^9/L. PLT count ≥75×10^9/L. Hemoglobin (HGB) ≥90 g/L.
    • Renal function Creatinine clearance ≥60 mL/min (based on Cockcroft-Gault equation for calculation)
    • Hepatic function Serum total bilirubin (TBIL) ≤1.5×ULN. Asparate aminotransferase (AST) and alanine transaminase (ALT) ≤2.5×ULN Serum ALB ≥30 g/L.
    • Coagulation function International normalized ratio (INR) or prothrombin time (PT) ≤1.5×ULN. Activated partial thromboplastin time (aPTT) ≤1.5×ULN.
    • For women of childbearing potential (WOCBP), the serum pregnancy test prior to the first dose must be negative and the potential participant must promise to use medically acceptable and effective methods of contraception. after signing the ICF until at least 6 months after the last dose.
    • Male participants of child-bearing potential must agree to use medically acceptable and effective methods of contraception after signing the ICF until at least 6 months after the last dose; in addition, male potential participants must agree not to donate sperm during this period.
    • Participants who understand and voluntarily sign the written ICF and are willing and able to comply with all trial requirements.
    • 1 Male or female aged 18 years or older when signing the ICF
    • 2 Patients with histologically confirmed high-risk NMIBC (Ta HG, T1, and/or CIS) who have not responded to BCG therapy after TURBT and are temporarily unwilling to undergo radical cystectomy are eligible. All visible papillary tumors must be resected, and significant CIS should also be resected or fulgurated. All pathological specimens must show predominantly urothelial (transitional cell) carcinoma features with <50% variant components (e.g., sarcomatoid, squamous, etc.); however, neuroendocrine and small cell atypia must be excluded. Patients with BCG-unresponsive NMIBC (? Persistent or recurrent CIS with or without recurrent Ta/T1 (non-invasive papillary lesions/tumor invading the subepithelial connective tissue layer) disease within 12 months of adequate BCG therapy;? High-grade Ta/T1 disease recurring within 6 months of adequate BCG therapy;? High-grade T1 disease as first assessed after the induction course of BCG therapy) are eligible. During the study, patients must voluntarily comply with study-mandated cystoscopy, urine cytology, and random biopsies.
    • 3 All toxic reactions from previous radiotherapy, chemotherapy or other treatments have recovered to ≤ Grade 1 (CTCAE 5.0) (except for alopecia); for subjects with other anti-tumor treatment-related toxicities > Grade 1 during the screening period, the investigator and the sponsor will discuss and decide whether to enroll.
    • 4 Eastern Cooperative Oncology Group (ECOG) performance status score was 0-2.
    • 5 Expected survival ≥ 24 weeks
    • 6 Laboratory test values must meet the following requirements (no hematopoietic growth factor therapy, blood transfusion, coagulation factor/PLT transfusion, or albumin [ALB] transfusion within 2 weeks prior to screening blood collection): a) Hematology: Absolute neutrophil count (ANC) ≥1.5 × 109/L. Platelet count (PLT) ≥75 × 109/L. Hemoglobin (HGB) ≥90 g/L. b) Renal function: Creatinine clearance ≥60 mL/min (calculated using the Cockcroft-Gault formula). c) Liver function: Serum total bilirubin (TBIL) ≤1.5 × ULN. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN. Serum ALB ≥30 g/L. d) Coagulation function: International Normalized Ratio (INR) or prothrombin time (PT) ≤1.5 × ULN. Activated partial thromboplastin time (aPTT) ≤1.5×ULN.
    • 7 For women of childbearing potential (WOCBP), the serum pregnancy test result before the first dose of the study drug must be negative and the patient must commit to taking medically recognized effective contraceptive measures for at least 6 months after signing the ICF and after the last dose.
    • 8 Male subjects of reproductive potential agree to take medically approved effective contraceptive measures for at least 6 months after signing the ICF and until the last dose; in addition, male subjects must agree not to donate sperm during this period.
    • 9 Understand and voluntarily sign the written ICF and are willing and able to comply with all trial requirements
    Exclusion criteria
    • Participants meeting any of the following criteria will not be allowed to participate in this study:
    • Participants meet the following criteria:
    • Concurrent or prior history of muscle-invasive (muscularis propria) or metastatic bladder cancer.
    • Urothelial carcinoma of the upper genitourinary tract or prostatic urethra within 24 months prior to investigational product.
    • Having received chemotherapy, biotherapy, endocrine therapy, targeted therapy, immunotherapy, investigational product or other anti-neoplastic therapies within 4 weeks prior to investigational product.
    • Having received radiotherapy within 2 weeks prior to investigational product.
    • Planning to receive any anti-neoplastic therapy other than the investigational products during this study.
    • A history of allergic reactions to HSV-1, IL-12, or anti-PD-1 antibodies or biological components similar to them, or known allergic reactions to any component of the T3011 formulation.
    • A history of brain metastasis or imaging-confirmed brain metastasis , leptomeningeal disease, or spinal cord compression.
    • Concurrent or prior history of other malignancies than that treated in this study.
    • History or evidence of high-risk cardiovascular diseases, including but not limited to:
    • Serious cardiac rhythm or conduction abnormalities.
    • Acute myocardial infarction, unstable angina, or stroke, etc., developing within 6 months prior to the first dose of the investigational products.
    • Coronary angioplasty or stenting within 6 months prior to the first dose of the investigational products.
    • New York Heart Association (NYHA) criteria-defined cardiac function > Class II; echocardiogram-documented cardiac valve morphological abnormalities (Grade ≥2).
    • Left ventricular ejection fraction (LVEF) lower limit of normal (LLN) of the study site, or 50% if no LLN is set at the site.
    • Poorly controlled blood pressure .
    • The following prior or concurrent immune disorders that in the investigator's opinion would pose unpredictable risks to the participants:
    • Immune-related pneumonia or other immune-related adverse reactions of Grade ≥3 developing with prior immunotherapy (including but not limited to PD-1/PD-L1).
    • Concurrent active immune diseases requiring treatment with systemic immunosuppressants (excluding autoimmune diseases not requiring intervention such as vitiligo and diseases treatable by other alternative drugs such as hypothyroidism that is treated with thyroid hormone replacement therapy originally), or concurrent immune diseases requiring treatment with systemic immunosuppressants that have the potential to recurrence (e.g., systemic lupus erythematosus).
    • Other concurrent diseases require treatment with systemic immunosuppressants.
    • Unexplainable fever >38.5℃ during the screening or on the day of treatment (fever judged as tumor-induced by the investigator is eligible for enrollment) that in the investigator's opinion will affect the participation in this trial or interfere with the efficacy assessment.
    • The following persistent or active infections: human immunodeficiency virus (HIV) antibody-positive, hepatitis B surface antigen [HBsAg] positive with HBV DNA level ≥2000 IU/mL, hepatitis C virus (HCV) antibody positive with detectable HCV RNA, and other active infections requiring systemic treatment.
    • Prior history of splenectomy or organ transplantation.
    • Having previously received treatment with oncolytic virus (e.g., T-VEC, CG0070).
    • Requiring oral or intravenous use of anti-herpes virus drugs, including but not limited to acyclovir, valaciclovir, penciclovir, famciclovir, ganciclovir, foscarnet, and cidofovir (except for those to be used locally, such as topically), during the study.
    • Participants with known psychiatric disorders that may affect compliance in trial or with poor compliance.
    • Participants with a history of drug abuse (including "recreational use") or substance abuse (including alcohol) within one year prior to signing ICF.
    • Being pregnant or breast feeding, or planning to become pregnant or give birth during this trial.
    • Having received any live attenuated vaccine within 4 weeks prior to investigational product or planning to receive such vaccines during the study.
    • Having undergone a major surgery.
    • Any diseases that at the investigator's discretion may confound the trial results, interfere with the participation in the entire trial, and/or would make participating in the trial not in the participant's best interest, or a medical history with treatment or laboratory abnormalities, or any other circumstances that would make it inappropriate for the participant to be enrolled.
    • 1Patients met the following criteria: a) Current or previous history of muscle-invasive (muscularis propria) or metastatic bladder cancer. b) Urothelial carcinoma of the upper urinary tract (kidney, renal collecting system, ureter) or prostatic urethra (including urethral CIS) within 24 months prior to study drug administration. c) Receipt of chemotherapy, biological therapy, endocrine therapy, targeted therapy, immunotherapy, investigational drug, or other anti-cancer treatment within 4 weeks prior to study drug administration (excluding TURBT instillation administered ≥14 days prior to study drug administration). d) Receipt of radiotherapy within 2 weeks prior to study drug administration.
    • 2Patients plan to receive anti-tumor treatment other than study drugs during the study
    • 3Patients with a history of allergic reaction to HSV-1, IL-12, or anti-PD-1 antibodies and similar biological components, or patients with known allergic reaction to any component of the T3011 formulation.
    • 4Patients with a history of brain metastases or brain metastases confirmed by imaging examinations, leptomeningeal disease, and spinal cord compression.
    • 5Patients with current or previous malignancies other than those treated in this study are excluded: a) malignancies that have been treated with curative intent, ≥5 years after the first dose of study drug, with no known active disease and a low potential risk of recurrence; b) adequately treated non-melanoma skin cancer or lentigo maligna with no evidence of disease; c) other carcinoma in situ that has been adequately treated and has no evidence of disease.
    • 6Those with a history or evidence of high-risk cardiovascular disease
    • 7Patients with the following immune diseases, which the investigator determines will pose unforeseen risks to the patient: a) Previous immune-related pneumonitis or other immune-related adverse reactions of Grade 3 or higher following immunotherapy (including but not limited to PD-1/PD-L1). b) Current active immune diseases requiring systemic immunosuppressant therapy, or immune diseases that may relapse and require systemic immunosuppressant therapy. c) Other diseases currently requiring systemic immunosuppressant therapy.
    • 8Unexplained fever > 38.5°C during the screening period or on the day of dosing (patients with fever caused by tumors are eligible for inclusion in the study if the investigator determines it is caused by the tumor) may affect the subject's participation in the study or interfere with the evaluation of the efficacy of the study, as determined by the investigator.
    • 9Currently have the following persistent or active infections: positive human immunodeficiency virus (HIV) antibodies, positive hepatitis B surface antigen [HBsAg] with HBV DNA titer ≥2000 IU/ml, positive hepatitis C virus (HCV) antibodies and HCV RNA, or other active infections requiring systemic treatment.
    • 10History of splenectomy or organ transplantation.
    • 11Previous oncolytic virus therapy.
    • 12Patients who need to take anti-herpes virus drugs orally or intravenously during the study, including but not limited to acyclovir, valacyclovir, penciclovir, famciclovir, ganciclovir, Fuxin Kane, cidofovir, etc. (except for topical use).
    • 13Patients currently suffering from known psychiatric disorders that may affect trial compliance or patients with poor compliance.
    • 14The patient has a history of drug use or substance abuse within one year before signing the ICF.
    • 15Are pregnant or breastfeeding, or plan to become pregnant or give birth during this trial
    • 16Patients who have received live attenuated vaccines within 4 weeks before study medication or plan to receive such vaccines during the study.
    • 17Patients who have undergone major surgery within 4 weeks before the study drug or are still recovering from the surgery or plan to undergo major surgery during the study

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Carolinas
    Myrtle Beach, SC, United States, 29572
    Investigator
    Neal Shore
    Status
    Recruiting
    Condition(s) Treated at Site
    Bladder