Eastern time. Each investigator or group of investigators at a clinical si te must obtain IRB approval for this protocol and submit IRB approval a nd supporting documentation to the CTSU Regulatory Office before they can enroll pati ents. Study centers can check the status of their registration packets by querying the Regulatory Support System (RSS) site registration status page of the CTSU member web site by entering credentials at https://www.ctsu.org. Requirements for protocol number site registration: • CTSU IRB Certification • CTSU IRB/Regulatory Approval Transmittal Sheet • IRB-approved consent form (if applicable) • CTSU RT Facilities Inve ntory Form (If applicable) NOTE: Per NCI policy all institutions that participate on protocols with a radiation therapy component must participate in the Radiological Physics Ce nter (RPC) monitoring program. If this form has been previously submitted to CTSU it does not need to be resubmitted unless updates have occurred at the RT facility. Patient enrollment will be facilitated usi ng the Oncology Patient Enrollment Network (OPEN). OPEN is a web-based registrati on system available on a 24/7 basis. All site staff will use OPEN to enroll patient s to this study. It is integrated with the CTSU Enterprise System for regulatory and roster data and, upon enrollment, initializes the patient position in the Rave database. OPEN can be accessed at https://open.ctsu.org or from the OPEN tab on the CTSU members’ side of the website at https://www.ctsu.org . Prior to accessing OPEN site staff should verify the following:  All eligibility criteria have been met within the protocol stated timeframes. Site staff should use the registration forms provided on th e CITN or CTSU web site as a tool to verify eligibility.  All patients have signed an appr opriate consent form and HIPAA authorization form (if applicable). Access requirements for OPEN: NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 27  Site staff will need to be registered with CTEP and have a valid and active CTEP- IAM account. This is the same account (use r id and password) used for the CTSU members' web site.  To perform registrations, the site user must have been assigned the 'Registrar' role on the CITN roster. Note: The OPEN system will provide the site with a printable confirmation of registration and treatment information. Pleas e print this confirmati on for your records. Further instructional informa tion is provided on the OPEN tab of the CTSU members’ side of the CTSU website at https://www.ctsu.org or at https://open.ctsu.org . For any additional questions contact the CT SU Help Desk at 1-888-823-5923 or ctsucontact@westat.com . Data collection for this study will be done excl usively through Medidata Rave. Access to the trial in Rave is granted through the iMed idata application to all persons with the appropriate roles in RSS. To access iMedidata/ Rave the site user must have an active CTEP IAM account ( https://eapps-ctep.nci.nih.gov/iam ). In addition, site users that are a member of the CITN must have the Rave roles (Rave CRA, Read-Only, Site Investigator) in RSS at the enrolling site. Upon initial site registration a pproval for the study in RSS, all persons with Rave roles assigned on the CITN roster will be sent a study invitation e-mail from iMedidata. To accept the invitation, site users mu st log into the Select Login (https://login.imedidata.com/selectlogin) using their CTEP-IAM user name and password, and click on the “accept” link in the u pper right corner of the iMedidata page. Please note, site users will not be able to access the study in Rave until all required Medidata and study specific trainings are comp leted. Trainings will be listed in the upper right pane of the iMedidata screen. Users who have not previously activated th eir iMedidata/Rave a ccounts will receive a separate invitation from iMedidata to ac tivate their account. Account activation instructions are located on the CTSU website, Rave tab unde r the Rave resource materials (Medidata Account Activation and Study Invitation Acceptance). Additional information on iMedidata/Rave is available on the CTSU website under the Rave tab at www.ctsu.org/RAVE/ or by contacting the CTSU Help Desk at 1-888-823-5923 or by e- mail at ctsucontact@westat.com . 5. TREATMENT PLAN 5.1 Agent Administration Patients with surgically incurable stage III or IV melanoma and tissue amenable to serial biopsy will undergo pretreat ment tumor biopsy and receive a 3-month course of INCB024360 administered as a twice daily continuous dosing oral regimen. The NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 28 MELITAC 12.1 vaccine has 3 components: 12-M P peptides, Peptide-tet, and Montanide ISA-51 VG vaccine adjuvant, which will be prepared together as an emulsion for administration. Three (3) mL of emulsion will be prepared. Two (2) mL of this emulsion will be administered, with 1 mL at each of 2 vaccine sites. At each site, half of each dose (0.5 mL) will be injected subcutaneously and half (0.5 mL) w ill be injected intradermally. The remaining 1 mL of the prepared emulsion will be discarded. On day 21, a week 3 tumor biopsy will be collected and the effects of inhibitor alone on the tumor microenvironment will be evaluated by comparing the pretreatment tumor biopsy to the day 21 tumor biopsy, assessing changes in IHC and gene signatures. Note: The biopsy on day 21 is mandatory. For pa tients with only one or two tumors approachable for biopsy, available tumor bl ocks from prior biopsies can serve as the pretreatment sample. Also on day 21, a vaccination regimen with MELITAC 12.1 multipeptide vaccine will begin, with vaccines administered on days 21, 28, 35, 56, 77, and 98 (Weeks 3, 4, 5, 8, 11, and 14. MELITAC 12.1, will be administered intradermally/subcutaneously at a fixed dose of 2.0 ml for 6 vaccinations. On day 42, tumor will be biopsied and the effect of continued INCB024360 plus vaccine on the tu mor microenvironment will be evaluated by comparing the week 3 tumor biopsy to the week 6 tumor biopsy, assessing changes in IHC and gene signatures. Patients will receive 3 weeks of INCB 024360, followed by continued INCB024360 plus 6 vaccinations with MELITAC 12.1. Patients who have disease progression while receiving anti-PD1 or anti-PD L-1 antibody treatment will be allowed to enroll and receive INCB024360 within 2-6 weeks of last antibody treatment administration. Patients enrolled within the 6 week window will be enrolled in Cohort B and administered INCB024360 orally at a dose of 100 mg twice da ily continuously up to day 98 (3 months) plus vaccines. Patients who enroll in the study after confirmed disease progression on anti-PD1/PDL-1 after 6 weeks of receiving the last dose of antibody will be enrolled in Cohort A and receive 300 mg BID of INCB024360 plus vaccines. Patients that show response at 3 months will be considered fo r additional INCB024360. As a lead-in to ensure safety and tolera bility of the combination of INCB024360 and MELITAC 12.1, the first 3 patients enrolled in the study will be at the dose of 300 mg bid staggering each patient’s enrollment by at le ast 2 weeks so that the first patient will receive 2 doses of the vaccine in comb ination with INCB024360 before the second patient starts the combination of agents. Enrollment will be halted afte r the first 3 patients are enrolled to allow for observation of any toxicity before opening further enrollment. The next nine patients will receive eith er 300 mg bid of INCB024360 or 100 mg bid (Table 5.1 ). For patient safety, if a Dose Limiting Toxicity (DLT) occurs in the first three patients treated at the 300 mg BID dose level of INCB024360 + MELITAC 12.1 vaccine, the subsequent 9 patients will be treated with the dose of either 300 mg BID or 100 mg of INCB024360 + MELITAC 12.1. If two DLTs occur in the first 6 patients treated at the NCI Protocol #: CITN-04 Version Date: 27 Jan 2016 29 300 mg dose of INCB024360 + MELITA C 12.1 the study will be stopped. Treatment will be administered on an outpatient basis.