CV301 Combined With PD-1/L1 Blockade in Patients With Locally Advanced or Metastatic Urothelial Bladder Cancer

Inclusion Criteria

• Age ≥ 18 years at date of ICF signature having the ability to comply with protocol.
• Histologically or cytologically documented locally advanced (T4b, any N; or any T, N 2-3) or metastatic (M1, Stage IV; or metastatic recurrence after locoregional treatment) UC (including renal pelvis, ureters, urinary bladder, urethra)
• Patients with mixed histologies were required to have a dominant transitional cell pattern.
• Locally advanced bladder cancer that was inoperable on the basis of involvement of the pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2-N3).
• Life expectancy ≥ 12 weeks.
• Measurable disease, as defined by RECIST v1.1. Previously irradiated lesions cannot be counted as target lesions unless there has been demonstrated progression in the lesion since radiotherapy and no other lesions are available for selection as target lesions.
• Demonstrate adequate organ function.
• For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception (i.e., one that results in a low failure rate [ 7 days prior to baseline imaging.
• Hormone-replacement therapy or oral contraceptives.
• Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to screening given that all AEs related to prior treatment have resolved to baseline or Grade 1.
• Active central nervous system (CNS) metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments or Leptomeningeal disease.
• Uncontrolled tumor-related pain:
• Patients requiring pain medication must be on a stable regimen at trial entry.
• Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to trial entry.
• Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) could be considered for loco-regional therapy if appropriate prior to enrollment.
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)

a. Patients with indwelling catheters (e.g., PleurX) are allowed.

• Uncontrolled hypercalcemia (>1.5 mmol/L ionized calcium or Ca >12 mg/dL or corrected serum calcium >ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy or denosumab:
• Patients who are receiving bisphosphonate therapy or denosumab specifically to prevent skeletal events and who did not have a history of clinically significant hypercalcemia are eligible.
• Patients who are receiving denosumab prior to enrollment have to be willing and eligible to receive a bisphosphonate instead while in the trial.
• Malignancies other than urothelial carcinoma within 3 years prior to Day 1, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, or ductal carcinoma in situ treated surgically with curative intent) or localized prostate cancer treated with curative intent and no intent for further treatment or incidental prostate cancer (T1/T2b, Gleason score ≤7 undergoing active surveillance and treatment naive).
• Pregnant and lactating women.
• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins, or aminoglycoside antibiotics or egg products, poxvirus-based vaccinations, or beef or bovine meat.
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or