Relationship Between Tumor Mutation Burden and Predicted Neo-antigen Burden in Patients With Advanced Melanoma or Bladder Cancer Treated With Nivolumab or Nivolumab Plus Ipilimumab (CA209-260)

Inclusion Criteria

• Subjects must have signed and dated an IRB approved written informed consent in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care.
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory tests, tumor biopsies, and other requirements of the study.
• Pathologically confirmed locally advanced or metastatic disease per the treating institution's standard of care of the following tumor types

Subjects with histologically confirmed locally advanced/unresectable or metastatic melanoma who meet all of the following criteria:

i. Subjects have received any number of prior lines of therapy or may be treatment naïve ii. If the subject has been treated with a prior line of therapy, they must have had disease progression or be refractory to treatment

OR

b. Subjects with histologically or cytologically confirmed locally advanced/unresectable or metastatic urothelial carcinoma (including mixed histologies of urothelial carcinoma with elements of other subtypes) of the renal pelvis, ureter, bladder or urethra (referred to broadly in this protocol as "bladder cancer") who meet the following criteria: i. Subjects must have disease progression or refractory disease after their prior line of therapy. Subjects must have had at least 1 platinum based chemotherapy regimen for the treatment of metastatic or locally advanced unresectable disease. Subjects may have received any number of prior lines of therapy OR

ii. Subjects with disease recurrence within 1 year of a platinum based neoadjuvant or adjuvant therapy for bladder cancer.

OR

iii. The subject actively refuses chemotherapy for the treatment of metastatic or locally advanced disease considered as standard treatment for this disease stage (i.e. a patient who has relapsed >1 year after treatment with neoadjuvant or adjuvant chemotherapy), despite being informed by the investigator about the treatment options. The subject's refusal must be documented.

• Subjects must have measurable disease by CT scans or MRI per RECIST 1.1 criteria. Radiographic tumor assessment must be performed within 28 days prior to first dose of study drug.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Age ≥ 18 years.
• Subjects must consent to allow for the acquisition of tumor sample prior to starting treatment on study (in most cases patients will require a tumor biopsy). This biopsy site may be the only site of measurable disease if the site is > 2 cm. The biopsy site must, in the opinion of the investigator, be likely to yield acceptable tumor sample for core biopsies as described in Appendix 4. It is also acceptable if tumor sample is obtained by excision biopsy or during surgery (i.e. if procedure was previously planned), provided the tumor sample can be processed as described in Appendix 4. In the case that a patient had a tumor sample acquired prior to consenting to the study and this tumor sample is acceptable for processing as described in Appendix 4 (i.e. frozen sample stored) and the tumor sample was acquired within 60 days of starting treatment, this is acceptable and a new biopsy will not be required.
• Willingness to adhere to the study visit schedule and prohibitions as specified in this protocol.
• Expected survival of at least 4 months.
• At the time of day 1 of the study, patients must have completed chemotherapy, targeted therapy, investigational therapy, other immunotherapy, radiation therapy or major surgery (requiring general anesthesia) at least 28 days before administration of the first dose of nivolumab. Patients undergoing minor surgical procedures and biopsies that do not require general anesthesia may begin receiving study therapy if sufficiently recovered as determined by the treating investigator. Patients may have received prior focal radiotherapy for pallia