Histological or cytological evidence of urothelial cancer of the bladder, urethra, ureter, or renal pelvis; differentiation with variant histologies (e.g., squamous cell differentiated) will be permitted provided that the predominant histology is urothelial carcinoma
Cohort A2: Transitional cell carcinoma of the urothelium including the bladder, urethra, renal pelvis, and ureter.
Have locally advanced (on TNM staging: T4b and any N, or any T and N2-3) or metastatic transitional cell carcinoma of the urothelium, including of the urinary bladder, urethra, ureter, and/or renal pelvis. The diagnosis must be histologically or cytologically confirmed.
Have histologically or cytologically confirmed locally advanced or metastatic transitional cell carcinoma of the urothelium (renal pelvis, ureter, urinary bladder or urethra)
Histologically confirmed muscle-invasive UC (also termed transitional cell carcinoma) of the bladder or upper urinary tract (i.e., renal pelvis or ureters)
Subject has histologically confirmed diagnosis of any one of the following cancers: (A) urothelial cancer (transitional cell cancer of the bladder, ureter or renal pelvis), (B) melanoma, or (C) squamous cell carcinoma of the head and neck.
Subjects with primary TCC of the ureter, urethra, or renal pelvis without TCC of the bladder are not allowed
(Part 2 only) Cohort 3: Have histologically or cytologically confirmed diagnosis of metastatic or locally advanced TCC of the urinary tract (bladder, urethra, ureter, renal pelvis) (T3b-T4 N0 M0, Tany N1-N3 M0, or Tany Nany M1) and are not candidates for surgery.
Patients with concurrent upper urinary tract (i.e. ureter, renal pelvis) non-invasive urothelial carcinoma
Cohort D: unresectable or metastatic urothelial carcinoma (urethra, bladder, ureters, or renal pelvis)
Have histologically or cytologically documented locally advanced unresectable or metastatic/recurrent urothelial carcinoma (including renal pelvis, ureters, urinary bladder, and urethra);
Histologically documented, locally advanced (T4b, any N; or any T, N 2?3) or metastatic urothelial carcinoma (mUC) (M1, stage IV) (also termed TCC or UCC of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra). Patients with mixed histologies are required to have a dominant transitional cell pattern. Locally advanced bladder cancer must be inoperable on the basis of involvement of pelvic sidewall or adjacent viscera (clinical stage T4b) or bulky nodal metastasis (N2?N3)
Dose Escalation, Renal insufficiency and CPI-Treated Expansion cohorts: Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
PRE-CHEMORADIATION SAMPLE COLLECTION: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
STUDY TREATMENT: Patients must have histologically proven primary carcinoma of the bladder or urethra or lower ureter (adenocarcinoma or transitional or squamous-cell carcinoma)
Histological or cytological evidence urothelial (transitional cell) carcinoma of the renal pelvis, ureter, bladder or urethra
Subject has histologically confirmed diagnosis of any one of the following cancers: urothelial cancer (transitional cell cancer of the bladder, ureter, urethra or renal pelvis), melanoma, squamous cell carcinoma of the head and neck, ovarian cancer, NSCLC (squamous, adenosquamous, or large cell), esophageal (squamous and adenocarcinoma) or gastric cancer, synovial sarcoma or MRCLS.
Histological or cytological evidence of transitional cell carcinoma or carcinoma in situ of the urothelium involving the bladder or prostatic urethra following treatment with BCG with the recommendation to proceed for cystectomy; minor histologic variants (< 50% overall) are acceptable; diagnosis must be within 1 year of study entry
Patients must have a histologically confirmed diagnosis of metastatic, progressive urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis
UROTHELIAL CARCINOMA EXPANSION COHORT: Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis from a CLIA-certified laboratory, with measurable disease by RECIST (version 1.1) including lymphadenopathy and visceral metastatic disease
Concurrent extra-vesical (i.e., urethra, ureter, or renal pelvis) non-muscle invasive transitional cell carcinoma of the urothelium
Histologically documented metastatic or surgically unresectable urothelial carcinoma; may include primary site from ureters, upper tract, renal pelvis, and bladder.
Documented urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra meeting all of the following criteria
Histological or cytological proof of urothelial carcinoma of the urethra, bladder, ureters, or renal pelvis
Histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis
Patients must have histologically or cytologically documented locally advanced/inoperable or metastatic urothelial bladder carcinoma (UBC), including renal pelvis, ureters, urinary bladder, and urethra\r\n* Note: mixed histology tumors allowed if predominant histology is urothelial carcinoma\r\n* Note: small cell or neuroendocrine carcinoma is not allowed if predominant
For the dose expansion part: Patients with histologically confirmed, locally advanced or metastatic urothelial carcinoma (transitional cell carcinoma) including urinary bladder, renal pelvis, ureters, urethra who are not candidates for or refuse standard therapy or whose disease progressed and for which standard anticancer treatment is no longer effective.
Histologically confirmed urothelial carcinoma of the bladder, ureter, urethra, or renal pelvis by the enrolling institution; patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the enrolling institution
Must have had invasive urothelial cancer at high risk of recurrence originating in the bladder, ureter, or renal pelvis
Participants must have stage IV, locally advanced or metastatic (T4b, any N; or any T, N2-3) urothelial bladder cancer or TCC arising in another location of the urinary tract, including urethra, ureter, and renal pelvis; the diagnosis must be histologically or cytologically confirmed; mixed histologies are permitted as long as TCC is the major component (i.e. > 50% of the pathologic specimen); pure or predominant squamous cell carcinomas or adenocarcinomas are not permitted
Cytologically or histologically confirmed evidence of transitional cell carcinoma of bladder, renal pelvis, ureter or urethra
Has a histologically or cytologically confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial carcinoma of the renal pelvis, ureter [upper urinary tract], bladder, or urethra. Both transitional cell and mixed transitional/non- transitional cell histologies are allowed, but transitional cell carcinoma must be the predominant histology.
Have histologically or cytologically confirmed, locally advanced or unresectable or metastatic urothelial (transitional cell) carcinoma of the bladder, urethra, ureter, or renal pelvis.
Have received prior systemic taxane therapy for transitional cell carcinoma (TCC) of the bladder, urethra, ureter, or renal pelvis in any setting (neoadjuvant, adjuvant, metastatic).
Histologically or cytologically confirmed urothelial carcinoma of the renal pelvis, ureter, urinary bladder, or urethra that is transitional cell or mixed transitional/nontransitional (predominantly transitional) cell type.
Histologically confirmed Transitional Cell Carcinoma of the Urothelium (TCCU) (i.e., cancer of the bladder, renal pelvis, ureter, or urethra). Subjects with Urothelial Carcinoma with squamous differentiation or mixed cell types are eligible.
Has histopathologically confirmed transitional cell carcinoma of the urothelium (bladder, urethra, or renal pelvis) with documented disease progression after 1-3 prior lines of systemic therapy
Histologically-confirmed diagnosis of urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra, that is transitional cell, or mixed transitional/non-transitional (predominantly transitional) cell type.
Histologically or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra.
benign low grade transitional cell carcinoma of the bladder
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified laboratory (lab)
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any CLIA certified lab
Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid; confirmation may be obtained from any CLIA certified lab
Histologically or cytologically confirmed urothelial carcinoma (confirmed at the enrolling institution) of the bladder, ureter, urethra, or renal pelvis; patients with mixed histologies are required to have a predominant urothelial component as reviewed by the pathologist at the treating institution
Evidence of metastatic or surgically unresectable transitional cell carcinoma of the urothelium involving the bladder,urethra,ureter or renal pelvis
Histologically- or cytologically-confirmed diagnosis of advanced/unresectable (inoperable) or metastatic urothelial cancer of the renal pelvis, ureter, bladder, or urethra (transitional cell and mixed transitional/non-transitional cell histologies)
Histologically or cytologically documented locally advanced or metastatic UBC (including renal pelvis, ureters, urinary bladder, and urethra)
Histologically- or cytologically-confirmed diagnosis of urothelial cancer of the renal pelvis, ureter, bladder, or urethra, that is transitional cell or mixed transitional/non-transitional (predominantly transitional) cell type
Patients must have locally advanced or metastatic predominantly urothelial carcinoma of the bladder, ureter, or urethra that is not amenable to curative surgical treatment
Patients must have histologically confirmed predominantly urothelial carcinoma of the bladder, ureter, or urethra
Histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, urethra)
Part B1 only: Patients with histological or cytological diagnosis of NSCLC, HNSCC, melanoma, urothelial bladder carcinoma (including renal pelvis, ureters, urinary bladder, and urethra), gastric or squamous cell carcinoma of the uterine cervix who progressed on or are intolerant to standard therapy, for which no standard therapy is available, or who decline standard therapy.
Histologically- or cytologically-confirmed diagnosis of locally advanced/unresectable (inoperable or not amenable to surgical treatment) and/or metastatic transitional cell urothelial cancer of the renal pelvis, ureter, urinary bladder, or urethra
Subjects with UC (including renal pelvis, ureter, bladder, urethra) after prior platinum-based therapy, or
Expansion Cohort 2: Subjects with UC with transitional cell histology (including renal pelvis, ureter, bladder, urethra) who have progressed on or after platinum-containing chemotherapy
Expansion Cohort 3: Subjects with UC with transitional cell histology (including bladder, renal pelvis, ureter, urethra) who are ineligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease
Expansion Cohort 4: Subjects with UC with transitional cell histology (including bladder, renal pelvis, ureter, urethra) eligible for cisplatin-based chemotherapy and have not received prior systemic chemotherapy for inoperable, locally advanced, or metastatic disease
Expansion Cohort 5: Subjects with UC with transitional cell histology (including renal pelvis, ureter, urinary bladder, urethra) who have radiographically progressed on or after one prior immune check-point inhibitor (anti-PD1 or anti-PD-L1) as the most recent therapy for the treatment of inoperable, locally advanced, or metastatic disease.
Subjects must have a pathologic diagnosis of advanced/metastatic urothelial cancer (carcinoma of the bladder, ureter, and/or renal pelvis) and must have failed at least 1 line of prior therapy in the metastatic/unresectable setting
Patients must have a histologically confirmed diagnosis of urothelial carcinoma of the bladder, urethra, ureter, or renal pelvis; confirmation may be obtained from any Clinical Laboratory Improvement Amendments (CLIA) certified lab or
Patient must have a histologically confirmed diagnosis of non-transitional cell carcinoma of the bladder, urethra, ureter, or renal pelvis including but not limited to squamous cell, neuroendocrine, adenocarcinoma including urachal and sarcomatoid; confirmation may be obtained from any CLIA certified lab
Patients in the expansion portion must have:\r\n* Histologically confirmed diagnosis of metastatic:\r\n** Urothelial carcinoma of the bladder, urethra, ureter, renal pelvis, OR\r\n** Clear cell renal cell carcinoma OR\r\n** Adenocarcinoma of the bladder OR\r\n** Non-resectable squamous cell carcinoma of the penis OR\r\n** Squamous cell carcinoma of the bladder AND\r\n* Patients with urothelial cancer or renal cell carcinoma must have progressive metastatic disease defined as new or progressive lesions on cross-sectional imaging; patients must have at least:\r\n** One measurable site of disease (according to RECIST criteria) or bone disease by NaF PET/CT
Participants must have histologically documented metastatic or locally inoperable advanced urothelial carcinoma (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3, or M1 disease. NOTE: Aberrant differentiation such as squamous, glandular (adenocarcinoma), and micropapillary are eligible unless the tumor is considered a pure histological variant according to the pathology report. Participants with small cell histology are not eligible.
UC Cohort (CIT-Treated): Participants with histologically confirmed incurable advanced transitional cell carcinoma of the urothelium (including renal pelvis, ureters, urinary bladder, and urethra) previously treated with anti-PD-L1/PD-1 with or without anti-CTLA-4 (investigational or approved)
Patients with pre-operative histologic confirmation of a bladder lesion other than transitional cell carcinoma
Stage IV, locally advanced or metastatic urothelial bladder cancer or transitional cell carcinoma arising in another location of the urinary tract, including urethra, ureter, and renal pelvis
Histologically documented, locally advanced (T4b, any N; or any T, N2-3) or metastatic urothelial carcinoma (mUC) (M1, Stage IV) (also termed transitional cell carcinoma [TCC] or urothelial cell carcinoma [UCC] of the urinary tract; including renal pelvis, ureters, urinary bladder, and urethra)