All patients must be receiving standard of care androgen deprivation treatment (surgical castration versus LHRH agonist or antagonist treatment); subjects receiving LHRH agonist or antagonist must continue treatment throughout the time on this study
Previous hormonal therapy, such as LHRH agonists (e.g., leuprolide, goserelin, buserelin, triptorelin) or LHRH antagonist (e.g. degarelix), anti-androgens (e.g., flutamide, bicalutamide, cyproterone acetate), estrogens (e.g., diethylstilbestrol [DES]), or surgical castration (orchiectomy)
Prior androgen deprivation (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least  days prior to study enrollment and given for =<  days duration\r\n* For example: Patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a . mg sustained release dose of leuprolide acetate is given ( month duration), then the expected duration of such a dose would be  days after the injection date; for a . mg leuprolide ( month duration), the discontinuation date would be  days after the injection date\r\n* Please note: Finasteride or dutasteride must be stopped before treatment but should not determine eligibility
Prior androgen deprivation therapy (luteinizing hormone-releasing hormone [LHRH] agonist and/or non-steroidal anti-androgen) is allowed if discontinued at least  days prior to Step  registration and given for =<  days duration\r\n* For example: patients on prior LHRH analogs (post-prostatectomy), the discontinuation date should be calculated based on the expected duration of the sustained release injection, not simply the injection date of the drug; for instance, if a . mg sustained release dose of leuprolide acetate is given ( month duration), then the expected duration of such a dose would be  days after the injection date; for a . mg leuprolide ( month duration), the discontinuation date would be  days after the injection date \r\n* Please note: finasteride or dutasteride must be stopped before treatment starts but prior usage will not affect eligibility
Prior therapy with a toll-like receptor (TLR) agonist, excluding topical agents.
Cohort B Safety Run-In (Ribociclib + PDR + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least  weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Expansion Cohort B (Ribociclib + PDR + Fulvestrant): Men are eligible, as long as on a GnRH agonist for at least  weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Men are eligible, as long as on a GnRH agonist for at least  weeks prior to study entry; men MUST remain on the GnRH agonist for the duration of protocol treatment
Subjects must not have received any previous androgen deprivation therapy (LHRH agonist or LHRH antagonist) or cytotoxic therapy for prostate cancer in the metastatic setting\r\n* Exceptions\r\n** Patients may have received no more than  days of anti-androgen (e.g. bicalutamide) in the metastatic setting prior to the start of study treatment.
A history of prior treatment with IL-, ipilimumab or prior cytotoxic T-lymphocyte antigen  (CTLA) inhibitor or agonist
Serum testosterone <  ng/dL. Subjects must continue primary androgen deprivation with an LHRH analogue (agonist or antagonist) if they have not undergone orchiectomy
Patients who have had chemotherapy, hormonal therapy (except LHRH agonist or antagonist), immunotherapy, radioisotope therapy, or RT within  days prior to start of the study agents
Patients may have received one prior depot injection of LHRH agonist or LHRH antagonist (degarelix) within  days prior to study entry. Patients who have received any other prior hormonal therapy or any chemotherapy for prostate cancer will be excluded. (Patients who have discontinued finasteride or dutasteride or testosterone supplement for at least  weeks will be allowed to enroll).
Patients who have had >  LHRH agonist or antagonist depot injection or received depot injection >  days before study entry.
Use of systemic chemotherapeutic (including but not limited to taxanes), hormonal, biologic, or radionuclide therapy for treatment of metastatic prostate cancer (other than approved bone targeting agents and GnRH agonist/antagonist) or any other investigational agent within  weeks before day .
For castration-only Cohort C, patients must have developed castrate resistant prostate cancer after progressing on first line hormone therapy with either surgical castration or LHRH agonist or LHRH agonist plus an anti-androgen
A history of prior treatment with ipilimumab or prior CD agonist or cytotoxic T-lymphocyte antigen  (CTLA-) inhibitor or agonist
No history of prior treatment with ipilimumab or prior tumor necrosis factor receptor superfamily, member  (CD) agonist or cytotoxic T-lymphocyte-associated protein  (CTLA-) inhibitor or agonist
Hormonal therapies acting on the hypothalamic-pituitary-gonadal axis (i.e., LHRH agonist/antagonist) are permitted. No other hormonal therapy is permitted;
In case of women, both premenopausal and postmenopausal patients are allowed to be included in study; menopausal status is relevant for the requirement of LHRH agonist (examples for use in this study include but not limited to goserelin, leuprolide or locally available treatment) to be used concomitantly with alpelisib and letrozole/fulvestrant
Testosterone =<  ng/dL (documented at any time while on LHRH agonist or antagonists or s/p orchiectomy)
Prior treatment with anti-cytotoxic T-lymphocyte antigen  (CTLA) monoclonal antibodies or prior CTLA- inhibitor or agonist or prior clusters of differentiation (CD) agonist or prior interferon-alfa is not allowed; other forms of prior treatment for melanoma (e.g., aldesleukin [IL-], 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  weeks prior to randomization
There are two patient populations eligible for the study: those who have not started any therapy with LHRH agonist or antagonist (or orchiectomy) (Early Induction Group) and those who have already started therapy with LHRH agonist or antagonist (or orchiectomy) within the  days prior to registration (Late Induction Group); patients must be registered within  days of first injection of the LHRH agonist or antagonist (or orchiectomy)
Patients who have not yet started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) and will not have an LHRH agonist injection until after randomization (early induction group) must have radiographic assessments of all disease including bone scan (or positron emission tomography [PET] scan) within  days prior to registration; patients who have started androgen deprivation therapy (LHRH agonist/antagonist or orchiectomy) prior to registration (late induction group) must have radiographic assessments including bone scan (or PET scan) within  days prior to start of androgen deprivation therapy (if scans have not been obtained prior to LHRH agonist/antagonist or orchiectomy they must be done within  days prior to registration); all disease must be assessed and documented on the Baseline Tumor Assessment Form; NOTE: Androgen deprivation therapy does not include treatment with anti-androgens such as bicalutamide or flutamide or five alpha reductase inhibitors such as finasteride or dutasteride
In the late induction group, patients must have had no more than  days of prior castration (medical or surgical) for metastatic prostate cancer prior to registration; the start date of medical castration is considered the day the patient first received an injection of a LHRH agonist/antagonist (or orchiectomy), not an oral antiandrogen\r\n* If the method of castration was luteinizing hormone releasing hormone (LHRH) agonists (i.e., leuprolide or goserelin), the patient must be willing to continue the use of LHRH agonist and add bicalutamide or TAK- (according to randomization) during protocol treatment\r\n* If the patient was on an antiandrogen (e.g. bicalutamide, flutamide), the patient must be willing to switch over to bicalutamide or TAK- (according to randomization); there is no limit on how many days a patient may have been on an antiandrogen (e.g. bicalutamide, flutamide) or a five alpha reductase inhibitor (e.g. finasteride or dutasteride) prior to going on study and no washout is required\r\n* If the method of castration was LHRH antagonists (i.e. Degarelix), the patient must be willing to switch to an LHRH agonist during protocol treatment
Patient must not be known to have hypersensitivity to TAK-, to TAK- metabolites, to bicalutamide, or to LHRH agonist
Subjects must have undergone orchiectomy, or have ongoing LHRH analogue therapy prior to drug initiation. Subjects on LHRH analogues must remain on these agents for the duration of the study.
Once randomized at day , subject must maintain ADT with an LHRH agonist or antagonist during study treatment or have a history of bilateral orchiectomy (i.e., medical or surgical castration).
Patients are ineligible if they have a history of prior treatment with ipilimumab, bevacizumab, or prior tumor CD agonist or CTLA- 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- or PD-L as per current protocol eligibility, although they are not currently commercially approved in the front line setting
Pre-/peri-menopausal women can be enrolled if amenable to be treated with the luteinizing-hormone releasing hormone (LHRH) agonist, goserelin. Individuals must have commenced treatment with goserelin or an alternative LHRH agonist at least  weeks prior to first dose of study drug. If individuals have received an alternative LHRH agonist prior to study entry, they must switch to goserelin on or before Cycle  Day  (CD) for the duration of the study
Previous participation in tremelimumab or ipilimumab clinical trial or prior treatment with a CD agonist or CTLA- inhibitor or agonist
On an LHRH agonist for at least  days, if pre-/peri-menopausal, and willing to switch to goserelin (Zoladex ) at time of randomization.
Prior hormonal therapy, such as LHRH agonists (e.g., goserelin, leuprolide), antiandrogens (e.g., flutamide, bicalutamide), estrogens (e.g., diethylstilbestrol [DES]), or bilateral orchiectomy
Patients must have undergone orchiectomy, or have been on LHRH agonists or antagonists, for at least  months prior to study entry. Patients on LHRH agonists/antagonists must remain on these agents for the duration of the study.
Patients who have received androgen deprivation therapy for greater than  days (LHRH-agonist or antagonist) for the treatment of their newly diagnosed metastatic disease prior to enrollment are not eligible for this study
Histologically confirmed prostate adenocarcinoma with metastasis either starting or recently started on LHRH analogue therapy; (late induction permitted within  months of starting LHRH analogue therapy or antiandrogen); no minimum PSA requirement for patients with measurable disease
Patients who are being treated with a GNRH antagonist should be willing to switch to a LHRH analogue after registration
At least a  week interval from previous prostate cancer treatment other than LHRH agonist/antagonist therapy, bisphosphonates, denosumab to the start of protocol therapy
COHORT A: A history of prior treatment with ipilimumab or prior CD agonist or cytotoxic T-lymphocyte-associated antigen  (CTLA-) inhibitor or agonist
COHORT B: A history of prior treatment with ipilimumab or prior CD agonist or CTLA- inhibitor or agonist
Prior treatment with an OX agonist and -BB agonist (for Part B/B)
At least a  week interval from previous prostate cancer treatment other than LHRH agonist/antagonist therapy, bisphosphonates, or denosumab to enrollment
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD) agonist or cytotoxic T-lymphocyte antigen  (CTLA-) inhibitor or agonist
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD) agonist or CTLA- inhibitor or agonist
If a patient enters the trial on androgen suppression therapy (AST) that consists of both an LHRH agonist and an oral antiandrogen, both agents should be continued throughout the study; if an antiandrogen is stopped prior to study entry, it should be stopped  weeks before for nilutamide and flutamide and  weeks before for bicalutamide to ensure that a withdrawal phenomenon does not interfere with interpretation of efficacy results
A history of prior treatment with ipilimumab or prior cluster of differentiation (CD) agonist or cytotoxic T-lymphocyte-associated protein  (CTLA-) inhibitor or agonist
A history of prior treatment with ipilimumab or prior CD agonist or cytotoxic T-lymphocyte-associated protein  (CTLA) 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) or cytotoxic T-lymphocyte-associated protein  (CTLA-) 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).
Ongoing gonadal androgen deprivation therapy with LHRH analogues or orchiectomy. Patients, who have not had an orchiectomy, must be maintained on standard dosing of LHRH analogue therapy at appropriate frequency for the duration of the study
Willingness to discontinue LHRH analogue therapy and for the duration of the study
Ongoing use of an LH-RH agonist (or antagonist); patients who agree to stop LH-RH agonist therapy will be eligible but may need to wait until their required washout period is over; patients whose washout period is greater than  weeks will not be eligible; duration of washout period varies with the formulation of the LH-RH agonist being used and should be  weeks after the next dose would be scheduled; specifically:\r\n* For patients receiving a monthly formulations of LH-RH agonist,  weeks must pass from the last dose before eligibility;\r\n* For patients receiving a -month depot formulation of LH-RH agonist,  weeks must pass from the last dose before eligibility;\r\n* For patients receiving a - month depot formulation of LH-RH agonist,  weeks must pass from the last dose before eligibility;\r\n* For patients receiving a - month depot formulation of LH-RH agonist,  weeks must pass from the last dose before eligibility;\r\n* For patients with an annual LH-RH implant,  weeks must pass after removal of the implant before eligibility
Prior treatment with a human DR agonist.
Patients are excluded if they have a history of prior treatment with ipilimumab, cluster of differentiation (CD) agonist, cytotoxic T-lymphocyte antigen  (CTLA-) inhibitor or agonist or bavituximab
Last effective dose of LHRH agonist/antagonist expired >  months prior to study entry; for example, a patient receiving LHRH agonist injection every  months would be eligible provided their last injection was >  months prior to day  of protocol therapy; a patient receiving LHRH agonist injections every  months will be eligible provided last injection was >  months prior to day  of protocol therapy
Use of LHRH agonist or antagonist treatment within  months prior to randomization.
Any history of prior treatment with ipilimumab or prior CD agonist or cytotoxic T-lymphocyte-associated antigen- (CTLA-) inhibitor or agonist
First dose of LHRH agonist or antagonist no more than  months prior to date of study content
Other investigational agents in addition to LHRH agonist/antagonist are allowed (e.g. novel anti-androgens, androgen synthesis inhibitors)
Patients must have prior bilateral orchiectomy or be on continuous LHRH analogue therapy for the duration of study
Ongoing treatment with any systemic therapy intended for the treatment of prostate cancer (e.g., antiandrogen or LHRH agonist or antagonist)