Men are eligible, as long as on a GnRH agonist for at least 6 weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Prior treatment with anti?cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) therapeutic agents (e.g. ipilimumab)
A history of prior treatment with IL-2, ipilimumab or prior cytotoxic T-lymphocyte antigen 4 (CTLA4) inhibitor or agonist
Received any prior treatment with CD137 agonists or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors.
Patients are excluded if they have a history of prior treatment with ipilimumab or CTLA-4 inhibitor.
A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist
No history of prior treatment with ipilimumab or prior tumor necrosis factor receptor superfamily, member 9 (CD137) agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
Patients are excluded if they have a history of prior treatment with ipilimumab, CTLA-4 inhibitor or agonist, nivolumab, PD-1 or PD-L1 inhibitor
Prior treatment with anti-cytotoxic T-lymphocyte antigen 4 (CTLA4) monoclonal antibodies or prior CTLA-4 inhibitor or agonist or prior clusters of differentiation (CD)137 agonist or prior interferon-alfa is not allowed; other forms of prior treatment for melanoma (e.g., aldesleukin [IL-2], anti-tumor vaccine, chemotherapy) are allowed if given before the resection(s) that make(s) the patient eligible for this trial, but these must have been completed at least 4 weeks prior to randomization
Patients are ineligible if they have a history of prior treatment with ipilimumab, bevacizumab, or prior tumor CD137 agonist or CTLA-4 inhibitor or agonist; patients may be treatment naive or have had one prior systemic therapy for metastatic disease as outlined in the eligibility criteria; patients may have received PD-1 or PD-L1 as per current protocol eligibility, although they are not currently commercially approved in the front line setting
Previous participation in tremelimumab or ipilimumab clinical trial or prior treatment with a CD137 agonist or CTLA-4 inhibitor or agonist
COHORT A: A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) inhibitor or agonist
COHORT B: A history of prior treatment with ipilimumab or prior CD137 agonist or CTLA-4 inhibitor or agonist
Prior treatment with an OX40 agonist and 4-1BB agonist (for Part B1/B2)
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or CTLA-4 inhibitor or agonist
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD)137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor or agonist
A history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated protein 4 (CTLA4) inhibitor or agonist
Patients who have received prior therapy with a TLR agonist Patients who have received experimental vaccines or immune therapies other than PD-(L)1 or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (e.g., Imlygic®) should be discussed with the Medical Monitor to confirm eligibility. Note: (prior treatment with a topical TLR agonist (e.g. imiquimod) is permitted).
Prior treatment with a human DR5 agonist.
Patients are excluded if they have a history of prior treatment with ipilimumab, cluster of differentiation (CD)137 agonist, cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor or agonist or bavituximab
Any history of prior treatment with ipilimumab or prior CD137 agonist or cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) inhibitor or agonist