| Eligibility |
Inclusion Criteria:
1. Participants who understand and voluntarily sign the written ICF, and are willing and
able to comply with all trial requirements.
2. Male or female, aged = 18 years at the time of signing the ICF.
3. Participants with a histologically confirmed diagnosis of NMIBC (Ta, T1 and/or Tis).
4. Participants with high risk NMIBC who have been diagnosed by cystoscopy, urine
cytology, and histopathology within 8 weeks prior to the first dose administration and
have failed or intolerant to BCG treatment after TURBT surgery, and are not suitable
or willing to undergo radical cystectomy.
5. BCG-failure include BCG refractory, recurrence or relapsing after BCG treatment, BCG
unresponsive and BCG intolerant.
6. All tumors should have no visible tumors after transurethral bladder tumor resection
(TURBT). If meeting the requirements for secondary resection, secondary resection need
to be done. It is recommended to perform secondary resection if the following
conditions are met: the first TURBT is insufficient, there is no muscle tissue in the
first resection specimen (excluding low-grade [Ta G1] tumors and pure in situ
cancers), T1 stage tumors, and high-grade [G3] tumors (excluding pure in situ
cancers); Secondary resection is recommended to be performed 2-6 weeks after the first
resection; Participants undergoing secondary resection must meet the requirement of no
visible tumors after surgery.
7. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.
8. Expected survival =3 months.
9. Sufficient hematology and terminal organ function were met within 4 weeks prior to the
first s treatment, for example, having sufficient bone marrow reserves and organ
function:
- Hematology (hematopoietic growth factor treatment or blood transfusion should not
be given within 2 weeks prior to the treatment of study drug): 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, Aspertate
aminotransferase (AST) and alanine transaminase (ALT) =3×ULN
- Coagulation function: International normalized ratio (INR) or prothrombin time
(PT) =1.5×ULN; Activated partial thromboplastin time (aPTT) =1.5×ULN
10. Women with fertility should agree to use contraceptive measures (such as intrauterine
devices (IUDs), contraceptives, or condoms) during the study period and within 6
months after the end of the study; Within 7 days prior to enrollment in the study, the
serum or urine pregnancy test was negative and must be a non lactating patient; Men
should agree to patients who must use contraceptive measures during the study period
and within 6 months after the end of the study period. Note: A female subject with
fertility is defined as a female subject who has not reached a postmenopausal state
after menarche (continuous amenorrhea for at least 12 months, with no other clear
cause other than menopause), and has not undergone surgery (i.e. bilateral
ovariectomy, fallopian tube resection, and/or hysterectomy) or other causes determined
by the researcher (such as underdeveloped Mullerian tubes) leading to permanent
infertility.
Exclusion Criteria:
Patients meeting one or more of the following criteria will be excluded:
1. The diagnosis is confirmed as muscle invasive bladder cancer (T2-T4).
2. Patients with concurrent upper and lower urinary tract epithelial carcinoma, lymph
node metastasis, or distant metastasis.
3. Pregnant and lactating female patients.
4. Having major surgery within 4 weeks prior to the first dose of the study drug, or
anticipate the need for major surgery rather than diagnosis after enrolling the study.
5. In addition to immediate instillation therapy after TURBT surgery, anti-tumor drug
treatments such as chemotherapy, radiation therapy, biological therapy, endocrine
therapy, targeted therapy, immunotherapy, etc. have been received within 4 weeks prior
to the first dose of the study drug (excluding nitroso urea, mitomycin C, oral
fluorouracil, small molecule targeted drugs, and traditional Chinese medicine with
anti-tumor indications). Nitrso urea or mitomycin C is within 6 weeks prior to the
first use of the study drug, and oral fluorouracil and small molecule targeted drugs
are within 2 weeks prior to the first use of the study drug or within 5 half-lives of
the drug (whichever is longer). Traditional Chinese medicine with anti-tumor
indications is within 2 weeks prior to the first dose of the study drug.
6. Patients who have received systemic corticosteroids (prednisone>10mg/day or equivalent
doses of similar drugs) or other immunosuppressive treatments within 14 days prior to
the first dose of the study drug; Excluding the use of local, ocular, intra-articular,
intranasal, and inhaled corticosteroids for treatment; Short term use of
corticosteroids for preventive treatment (such as preventing contrast agent
allergies).
7. Taking live attenuated vaccines within 4 weeks prior to the first dose of the study
drug, or it is expected that live attenuated vaccines will be vaccinated during the
study period.
8. Participants who have previously received oncolytic virus therapy (such as T-vec,
T3011, etc.), gene therapy, cell therapy, and tumor vaccines.
9. Participants have a history of splenectomy or organ transplantation.
10. Participants with the malignant tumors other than the disease treated in this study,
except for the following:
- Malignant tumors that have undergone treatment with the aim of cure, at least
more than 5 years from the drug treatment, have no known active diseases, and
have a low potential risk of recurrence;
- Fully treated non-melanoma skin cancer or malignant freckle like nevi with no
evidence of disease;
- In situ cancer with sufficient treatment and no evidence of disease.
11. 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 gross hematuria.
12. Indwelling ureteral stent or having a history of bladder ureteral reflux disease.
13. Major cardiovascular diseases, such as New York Heart Association heart disease (grade
II or higher), myocardial infarction within the first three months of enrollment,
unstable arrhythmia or unstable angina.
14. Having the history of autoimmune diseases, including but not limited to myasthenia
gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid
arthritis, inflammatory bowel disease, vascular thrombosis associated with
antiphospholipid syndrome, Wagner's granulomatosis, Sjogren's syndrome, Guillain Barre
syndrome, multiple sclerosis, vasculitis, or glomerulonephritis. Except for patients
with hypothyroidism or diabetes who have good control of alternative treatment.
15. Persistent or active infections exist, and drug treatment and control are still not
ideal; Including but not limited to: active pulmonary tuberculosis, non negative AIDS
virus (HIV) antibody, positive hepatitis B surface antigen (HBsAg), hepatitis B virus
deoxyribonucleic acid (HBV DNA) quantity = the lower limit of the laboratory test in
the research center, hepatitis C virus antibody (HCV Ab) positive and hepatitis C
virus RNA quantity = the lower limit of the laboratory test in the research center.
16. Participants who require oral or intravenous use of anti herpesvirus drugs during the
study period (including but not limited to acyclovir, valaciclovir, penciclovir,
famciclovir, ganciclovir, foxinkane, cedofovir, etc.) (excluding local use such as
topical use).
17. Participants with the history of allergic reactions to HSV-1, IL-12, or anti PD-1
antibodies and similar biological components, or those known to have allergic
reactions to any component of T3011.
18. Fever above 38.5 ? with no explained reason during the screening period, washout
period/baseline period, or on the day of administration (the researcher determines
that fever caused by tumors can be included), according to the researcher's judgment,
may affect the patient's participation \in this trial or interfere with the evaluation
of efficacy.
19. In the period of recurrent herpes simplex virus infection, there are corresponding
clinical manifestations, such as lip herpes, herpetic keratitis, herpetic dermatitis,
genital herpes, etc.
20. Participants who have previously developed non infectious pneumonia/interstitial
pneumonia or are intolerant to immunotherapy drugs (including but not limited to anti
PD-1/PD-L1 antibodies) (including but not limited to developing = grade 3 immune
related adverse events [irAEs]) (excluding endocrine related irAEs that can be stably
controlled through hormone replacement therapy).
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