Please select the eligibility criteria that correspond to the clinical trial below.
Title: A Single-Arm, Multicenter Phase 2 Study of BGB-A317 in Patients With Previously Treated PD-L1+ Locally Advanced or Metastatic Urothelial Bladder Cancer
Brief Summary: This was a single-arm, multicenter, Phase 2 study to evaluate the efficacy and safety of the anti- programmed cell death-1(PD-1) monoclonal antibody BGB-A317 in participants with PD-L1+, locally advanced or metastatic Urothelial Bladder Cancer (UBC) who have progressed during or following a platinum-containing regimen


Options:
A: Inclusion Criteria:

* Patients with histologically or cytologically documented, unresectable, Stage IV transitional cell carcinoma of the urothelium who have not been previously treated with first-line chemotherapy.
* Patients eligible or ineligible for cisplatin-based chemotherapy. Cisplatin ineligibility is defined as meeting 1 of the following criteria: • Creatinine clearance (calculated or measured) \<60 mL/min calculated by Cockcroft-Gault equation (using actual body weight) or by measured 24-hour urine collection for determination • Common Terminology Criteria for Adverse Events (CTCAE) Grade ≥2 audiometric hearing loss • CTCAE Grade ≥2 peripheral neuropathy • New York Heart Association ≥Class III heart failure.
* Tumor PD-L1 status, with Immunohistochemical (IHC) assay confirmed by a reference laboratory, must be known prior to randomization.

Exclusion Criteria:

* Prior exposure to immune-mediated therapy, including but not limited to, other anti cytotoxic T-lymphocyte-associated protein 4 (CTLA 4), anti-PD-1, anti-PD-L1, or anti-PD-L2 antibodies, including therapeutic anticancer vaccines. Prior local intervesical chemotherapy or immunotherapy is allowed if completed at least 28 days prior to the initiation of study treatment.
* History of allogenic organ transplantation that requires use of immunosuppressive agents.
* Active or prior documented autoimmune or inflammatory disorders. The following are exceptions to this criterion: • Patients with vitiligo or alopecia • Patients with hypothyroidism (eg, following Hashimoto syndrome) stable on hormone replacement • Any chronic skin condition that does not require systemic therapy • Patients without active disease in the last 3 years may be included but only after consultation with AstraZeneca • Patients with celiac disease controlled by diet alone may be included but only after consultation with AstraZeneca.
* Brain metastases or spinal cord compression unless the patient's condition is stable and off steroids for at least 14 days prior to the start of study treatment. Patients with suspected or known brain metastases at screening should have an MRI (preferred)/CT, preferably with IV contrast to access baseline disease status.
* Active infection including tuberculosis, hepatitis B, hepatitis C, or human immunodeficiency virus (HIV).
* Current or prior use of immunosuppressive medication within 14 days before the first dose of investigational product (IP). The following are exceptions to this criterion: • Intranasal, inhaled, topical steroids, or local steroid injections (eg, intra articular injection) • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent • Steroids as premedication for hypersensitivity reactions (eg, CT scan premedication).
* Receipt of live attenuated vaccine within 30 days prior to the first dose of IP. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of IP.
B: For more information regarding BMS clinical trial participation, please visit www.BMSStudyConnect.com

Inclusion Criteria:

* Subjects with histologically or cytologically confirmed locally advanced or metastatic disease of the following tumor types:
* Triple Negative Breast Cancer
* Gastric Cancer
* Pancreatic Cancer
* Small Cell Lung Cancer
* Bladder Cancer
* Ovarian Cancer
* Subjects must have measurable disease
* Eastern Cooperative Oncology Group (ECOG) of 0 or 1
* Adequate hematological and organ function as confirmed by laboratory values

Exclusion Criteria:

* Active brain metastases or leptomeningeal metastases
* Subjects with active, known or suspected autoimmune disease
* Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment
* Prior therapy with experimental anti-tumor vaccines; any T cell co-stimulation or checkpoint pathways, such as anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, including Ipilimumab; or other medicines specifically targeting T cell is also prohibited
C: Inclusion Criteria:

* Participants with histologically documented locally advanced (tumor \[T\] 4b, any node \[N\]; or any T, N 2-3) or metastatic (M1, Stage IV) urothelial or non-urothelial carcinoma of the urinary tract
* Participants with measurable and/or non-measurable disease according to RECIST v1.1
* Participants must have progressed during or following treatment with at least one prior (and not more than 3) treatments for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
* If available, a representative formalin-fixed paraffin-embedded (FFPE) tumor specimen block should be submitted
* Eastern cooperative oncology group (ECOG) performance status 0, 1 or 2

Exclusion Criteria:

* Treatment with more than three prior lines of systemic therapy for inoperable, locally advanced or metastatic urothelial or non-urothelial carcinoma of the urinary tract
* Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 4 weeks prior to study treatment initiation

  1. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were not on active drug in that prior trial are eligible
  2. Participants who were in another clinical trial with therapeutic intent within 4 weeks of study treatment initiation but were in the follow-up phase of that prior trial and had stopped receiving active drug 4 or more weeks before study treatment initiation are eligible
* Malignancies other than the one studied in this protocol within 5 years prior to Cycle 1, Day 1
* Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol
* Significant renal disorder indicating a need for renal transplant
D: Key Inclusion Criteria:

1. Participants with histologically or cytologically documented locally advanced or metastatic transitional cell carcinoma (TCC) of the urothelium
2. Disease progression during or following treatment with at least one platinum-containing regimen for inoperable locally advanced or metastatic urothelial carcinoma or disease recurrence
3. Participants must submit archival tumor tissue for determination of program death ligand-1 (PD-L1) expression and other biomarker analyses. PD-L1 expression will be assessed centrally, and participants who are tested as PD-L1 high are eligible.
4. Participants must have at least one measurable lesion as defined per RECIST version 1.1 assessed by the investigator
5. Male or female, aged ≥18 years on day of signing informed consent
6. Participants have voluntarily agreed to participate by giving written informed consent
7. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
8. Life expectancy ≥12 weeks
9. Participant must have adequate organ function as indicated by the following screening laboratory values obtained within 7 days prior to the first study treatment

   1. Absolute neutrophil count (ANC) ≥1.5×109/L
   2. Platelets ≥100×109/L
   3. Hemoglobin ≥9 g/dL or ≥5.6 mmol /L (Note: Criteria must be met without a transfusion within 14 days of obtaining the sample)
   4. Calculated creatinine clearance ≥ 30 milliliter (mL)/min (Cockcroft-Gault formula, see Appendix 5)
   5. Serum total bilirubin ≤ 1.5 X upper limit of normal (ULN) (total bilirubin must be \<4 X ULN for participants with Gilbert's syndrome)
   6. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 X ULN OR ≤ 5 X ULN for participants with liver metastases
10. Female participants are eligible to enter and participate in the study if they are of:

    1. Non-childbearing potential (ie, physiologically incapable of becoming pregnant), including any female who i) Has had a hysterectomy ii) Has had a bilateral oophorectomy (ovariectomy) iii) Has had a bilateral tubal ligation iv) Is post menopausal (total cessation of menses for ≥1 year)
    2. Childbearing potential, has a negative serum pregnancy test at screening (within 7 days before the first investigational product administration), not be breast feeding, and agree to remain abstinent (refrain from heterosexual intercourse) or uses adequate contraceptive methods that result in a failure rate of \<1% per year before study entry and throughout the study until 120 days after the last investigational product administration
11. Male participants are eligible to participate in the study if they are vasectomized or agree to use contraception during the study treatment period and for at least 120 days after the last dose of study drug

Key Exclusion Criteria:

1. History of severe hypersensitivity reactions to other humanized monoclonal antibodies
2. Prior active malignancy within 2 years prior to Cycle 1 Day 1.
3. Prior therapies targeting PD-1 or PD-L1.
4. Active brain or leptomeningeal metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments.
5. Participants with active autoimmune diseases or history of autoimmune diseases that may relapse should be excluded.
6. Participants should be excluded if they have conditions requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration.
7. Has history of interstitial lung disease or non-infectious pneumonitis except for those induced by radiation therapies
8. With severe chronic or active infections (including tuberculosis infection, etc) requiring systemic antibacterial, antifungal or antiviral therapy within 14 days prior to first dose of study drug.
9. With uncontrollable pleural effusion, pericardial effusion or ascites requiring pleurocentesis or abdominal tapping less than 4 weeks
10. Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within the previous 3 months, unstable arrhythmias, or unstable angina
11. Known history of Human Immunodeficiency Virus (HIV)
12. Participants with untreated chronic hepatitis B or chronic hepatitis B virus (HBV) carrier with HBV deoxyribonucleic acid (DNA) ≥500 IU/mL (or 2.5 × 103 cps/mL), or active hepatitis C should be excluded. Participant with inactive hepatitis B surface antigen (HBsAg) carrier, active HBV infection with sustained anti-HBV suppression (HBV DNA \<500 IU/mL or 2.5 × 103 cps/mL) and participants whose hepatitis C has been cured (hepatitis C virus \[HCV\] ribonucleic acid \[RNA\] is lower than detection limit) can be enrolled
13. Underlying medical conditions that, in the investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity determination or adverse events (AEs)
14. Prior chemotherapy, radiotherapy, immunotherapy or any investigational therapies (including Chinese herbal medicine and Chinese patent medicines) used to control cancer within 2 weeks of Cycle 1 Day 1. AEs associated with these therapies must be Grade 0-1, baseline or stabilized (except for alopecia)
15. Prior allogeneic stem cell or solid organ transplant
16. Administration of a live or attenuated vaccine within 4 weeks prior to study drug administration
17. Major surgical procedure other than for diagnosis within 28 days prior to study drug administration

NOTE: Other protocol defined Inclusion/Exclusion criteria may apply.

Answer: D