Study of 2141-V11 in People With Non-muscle Invasive Bladder Cancer That Did Not Respond to Standard Treatment

If during Period 1 treatment, the treating physician notices recurrent disease in the bladder, the patient should undergo a biopsy or TURBT. If the pathology returns as HG Ta or CIS, the patient can resume treatment. If pathology returns as HG T1, the patient will be removed from treatment. If a high-grade recurrence occurs during period 2 or 3 treatments, the patient will be removed from treatment.

Cohort B is organized into two parts. Cohort B Part 1 is the completed safety assessment of fixed-dose intratumoral 2141-V11 (10 mg) monotherapy. Cohort B Part 2 is a randomized, open-label, pilot Phase II expansion employing a selection design to evaluate the clinical efficacy of intratumoral 2141-V11 (10 mg) in combination with intravesical gemcitabine (2000 mg in 100 mL) compared to intravesical gemcitabine monotherapy (2000mg in 100 mL) in subjects with BCG-naïve high-grade Ta NMIBC. Subjects will be randomized 1:1 to the combination arm or the gemcitabine monotherapy arm.

***Continuation of Inclusion/Exclusion Criteria

Known additional malignancy that has had progression or has required active treatment in the last three years. Exceptions include:

• Basal cell carcinoma of the skin
• Squamous cell carcinoma of the skin that has undergone potentially curative therapy
• In situ cervical cancer
• History of prostate cancer treated with definitive intent (surgical or radiation therapy), provided that the following criteria are met: stage T2N0M0 or lower with a Gleason score ≤7 and prostate-specific antigen (PSA) undetectable for at least 1 year while off androgen deprivation therapy, that was either treated with definitive intent or untreated in active surveillance that has been stable for the past year prior to study enrollment
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e., with use of disease-modifying agents, corticosteroids, or immunosuppressive agents). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Diagnosis of immunodeficiency, concurrent immune suppressive disease, or is receiving systemic corticosteroid therapy or any other form of immunosuppressive therapy within 4 weeks prior to the planned first dose of trial treatment. The use of physiologic doses of corticosteroids as replacement therapy (for adrenal or pituitary insufficiency, etc.) is acceptable. Topical and inhaled corticosteroids in standard doses are acceptable.
• Known contraindications to intravesical therapy:
• Febrile illness, symptomatic urinary tract infection, or persistent gross hematuria
• Traumatic catheterization or gross hematuria on day of treatment
• Active infection requiring systemic therapy, including active or intractable urinary tract infection within 4 weeks prior to the first dose of trial treatment
• Severe infection within 4 weeks prior to the first dose of trial treatment, including, but not limited to, hospitalization for complications of infection, bacteremia, or severe pneumonia
• History of (non-infectious) pneumonitis that required steroids or current pneumonitis
• History of Human Immunodeficiency Virus (HIV) infection (e.g., positive HIV-1/2 antibodies)
• Active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C [e.g., HCV RNA (qualitative) detected] infection; subjects with past/resolved Hepatitis B Virus (HBV) infection (defined as having a negative HBsAg and a positive antibody to Hepatitis B coreantigen) or Hepatitis C Virus (HCV) infection are eligible only if polymerase chain reaction (PCR) testing is negative for HBV DNA or HCV RNA, respectively (must be obtained within 28 days prior to treatment initiation) Pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment
• History of stroke or intracranial hemorrhage within 6 months prior to enrollment
• History of pulmonary embolism or any other thromboembolic event within 6 months prior to enrollment
• History of undergoing an allogeneic tissue/solid organ transplant
• History or current evidence of any condition, therapy, or laboratory abnormality that might interfere with the subject's participation for the full duration of the trial, interfere with the subject's ability to cooperate with the requirements of the trial, confound the results of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator