A Phase I/II Study of JL19001 Injection Alone or in Combination With BCG in Subjects With High Risk Non-Muscle Invasive Bladder Cancer.

Обзор

Phase Ia, an open-label, sequential, dose escalation study to evaluate the tolerability and safety of JL19001 Injection alone in subjects with high risk NMIBC. The investigators plan to test 3 dose levels, 100, 200, and 400 μg in the Phase Ia study. A traditional 3 + 3 dose escalation design will be used. Eligible subjects will be sequentially enrolled and will be observed for DLT(s) during the DLT monitoring period (Day 1 \~ 21).

Вмешательства

• Препарат JL19001 Injection
  JL19001 Injection (100, 200, or 400 μg) will be administrated weekly for 6 consecutive weeks during induction treatment period, and then weekly for 3 consecutive weeks at month 3, 6, 9, 12, 18, 24, 30 and 36 during extension treatment period until disease progression, occurrence of unacceptable toxicity, withdrawal of informed consent, lost to follow-up, death, other reasons for withdrawal from treatment, or the end of treatment, whichever occurs earlier.

Первичные конечные точки

• Number of participants with reported Dose-limiting toxicity (DLT) [Срок оценки: Within 21 days after the first administration]
• Rate of adverse events [Срок оценки: Up to 3 years]
• Determine the recommend dose for combination for JL19001 injection [Срок оценки: Up to Month 36]

Вторичные конечные точки (11)

• Determination of JL19001 concentrations [Срок оценки: From the first administration to Week 6.]
• Detect anti-JL19001 antibodies in serum [Срок оценки: Up to 3 years]
• Determination of lymphocyte cell counts (cells/μL) in blood. [Срок оценки: From the first administration to Week 6.]
• Determination of CD8 T cell counts (cells/μL) in blood [Срок оценки: Time Frame: From the first administration to Week 6.]
• Determination of NK cell counts (cells/μL) in blood [Срок оценки: From the first administration to Week 6.]
• Radical cystectomy rate [Срок оценки: Up to 3 years.]
• Disease-free rate [Срок оценки: Up to 3 years.]
• Duration of complete response [Срок оценки: Up to 3 years.]
• Duration of disease-free survival [Срок оценки: Up to 3 years.]
• Time to cystectomy [Срок оценки: Up to 3 years.]
• Time to progression [Срок оценки: Up to 3 years.]

Критерии участия

Критерии включения

• Subjects should voluntarily sign the informed consent, and agree to comply with all protocol-specified procedures .
• Male or female patients ≥18 years of age at the time of signing the ICF.
• Life expectancy ≥ 2 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2.
• Previous pathological biopsy was diagnosed as high-risk NMIBC.
• Cystoscopy showed complete resection of the lesion or the residual lesion is only CIS within 6 weeks prior to initial administration; For T1 lesions, postoperative pathological results must show the presence of bladder muscle layer.
• After fully understanding the benefits, risks, and alternatives of radical cystectomy, the subject voluntarily chooses not to undergo the surgery; or the subject is deemed unsuitable for radical cystectomy by the researcher
• Subjects with fertility and their partner should use contraception during the study treatment period and within 12 weeks after the end of the study treatment period. Non-surgical sterilized female subjects of reproductive age must be negative for serum HCG within 7 days prior to initial administration and must be non-lactating.

Критерии исключения

• 1\. Individuals who are allergic to any component of the investigational product.

2\. Received surgical treatment or radiotherapy for bladder lesions within 2 weeks prior to initial administration

3\. Any of the following clinical laboratory values During the screening period Hematology:absolute neutrophil count (ANC) < 1.5 ×109/L, platelets < 100 × 109/L, Hemoglobin<90 g/L(Within 14 days prior to screening, no whole blood transfusion, component blood transfusion, or drugs such as colony stimulating factors \[For example: Granulocyte Colony-Stimulating Factor,Granulocyte-Macrophage Colony-Stimulating Factor,Erythropoietin,Thrombopoietin\] have been administered.) renal function:Creatinine> 1.5×upper limit of normal(ULN)or Creatinine Clearance≥ 60mL/min(Calculate according to the Cockcroft-Gault formula); liver function(No history of liver protection treatment within 7 days prior to screening examination):Aspartate Aminotransferase > 2.5 × ULN;Alanine Aminotransferase > 2.5 × ULN;Total Bilirubin > 1.5× ULN; ECG examination: QT interval corrected by Fridericia (QTcF) > 450ms for males, QTcF > 470ms for females; Coagulation function: Activated Partial Thromboplastin Time > 1.5 × ULN; International Normalized Ratio > 1.5 × ULN; Prothrombin Time > 1.5 × ULN;

4\. History of or evidence of muscle-invasive, locally advanced, metastatic and/or extravesical bladder cancer (inclusive of the prostatic urethra).

5\. There are contraindications to cystoscopy and/or urethroscopy, such as urethral stricture, urinary tract infection (UTI) (referring to symptomatic infection with positive urine culture), gross hematuria, and small bladder capacity, etc;

6\. Bladder dysfunction during the screening period, such as severe urinary incontinence or overactive bladder (OAB); bladder perforation detected during the screening period through cystoscopy or imaging examination;

7\. During the screening period, if upper urinary tract tumors are detected during an upper urinary tract examination, or tumors in the prostatic urethra are detected during cystoscopy, or other malignant tumors are found within 5 years of the first dose, with the exception of skin basal cell carcinoma, squamous cell carcinoma, and cervical carcinoma in situ that have achieved complete remission or been effectively controlled through treatment, as well as Stage I/II cancers that have received adequate treatment, or stable prostate cancer that is under active monitoring in complete remission or well-managed through androgen therapy

8\. Symptomatic congestive heart failure, New York Heart Association (NYHA) class III or IV heart failure, or other severe cardiac dysfunction, which the investigator deems clinically significant.

9\. Severe/unstable angina pectoris, or myocardial infarction within 6 months prior to study entry.

10\. History or evidence of uncontrollable central nervous system disease.

11\. Past medical history or examination suggests active tuberculosis within 1 year prior to initial administration;

12\. Severely infected people who need to be controlled by antibiotics, antivirals or antifungals;

13\. Have a history of immunodeficiency, including HIV seropositivity, other acquired or congenital immunodeficiency diseases.

14\. The subject had received systemic glucocorticoid treatment within 2 weeks prior to the first administration of the test drug, except for the following situations: the hormone dose was ≤ 10mg/day in prednisone equivalent; local, inhaled, or intranasal use of glucocorticoids; and subjects with contrast medium allergy received prophylactic one-time use of glucocorticoids before undergoing imaging enhancement examination;

15\. History of active autoimmune disease;

16\. Active hepatitis B (HBe-Ag positive and HBV DNA>=500 IU/mL), hepatitis C (HCV antibody positive and HCV RNA higher than the lower limit of assay detection)

17\. Received any other anti-tumor treatments within 4 weeks prior to the first dose, including systemic chemotherapy, small molecule targeted therapy, radiotherapy, and Chinese herbal medicine with anti-tumor effects, except for immediate bladder instillation chemotherapy performed after TURBT ≥ 14 days before dosing; Received immune checkpoint inhibitor therapy and antibody therapy within 6 months prior to the first dose;

18\. The study is undergoing treatment in other clinical trials or has ended until less than 4 weeks after the first administration of the study;

19\. The presence of other serious physical or mental illness, abnormal laboratory tests, and other factors that may increase the risk of participating in the study or interfere with the study results; And any other conditions that the investigator deems inappropriate for participation in this study.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• West China Hospital of Sichuan University — Чэнду

Идентификаторы

NCT: NCT07483970 · JL19001-NMIBC-101 · 2025LP02620

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗