Patients must have histologically or cytologically confirmed stage IV or unresectable stage III BRAF V600E or BRAF V600K mutant melanoma Patients must have unresectable stage III or stage IV disease Patients must have pathologically confirmed melanoma that is either stage IV or unresectable stage III; patients may have primaries of cutaneous, mucosal or unknown origin; patients with uveal (ocular) primary are not eligible Patients with unresectable or metastatic stage III B/C or IV melanoma. Patients enrolled under this version of the protocol must also have progressed on prior anti-PD-1 therapy, according to RECIST 1.1 criteria. Patients who progressed within 3 months of treatment start are excluded. Subjects must have histologically confirmed metastatic melanoma with measurable (by RECIST v1.1), stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease that is accessible for injection. Stage IV melanoma for which surgery is not recommended. Histologically-confirmed diagnosis of advanced (unresectable Stage III) or metastatic (Stage IV) melanoma excluding mucosal, or ocular melanoma (or a histologically or cytologically-documented locally-advanced or metastatic solid malignancy in Parts 4 and 5) Participants must have histologically or cytologically confirmed stage IV melanoma or recurrent stage IIIc melanoma following primary treatment of surgery and prior treatment or consideration of adjuvant therapy Participants must have a clinical indication for resection of metastatic melanoma; patients will be informed about other treatment options for stage IV melanoma including Braf inhibitors and antibodies to CTLA-4 Participants must have histologically or cytologically confirmed stage IV uveal melanoma Has a histologically confirmed diagnosis of unresectable stage III or metastatic melanoma not amenable to local therapy Have histologically- or cytologically-confirmed unresectable stage III or stage IV melanoma not amenable to local therapy Histologically confirmed Stage IV (metastatic) or unresectable Stage IIIc (locally advanced) melanoma Histologically confirmed unresectable stage III or stage IV melanoma (American Joint Committee on Cancer [AJCC] 7th edition classification); cutaneous melanoma and mucosal melanoma will be eligible American Joint Committee on Cancer (AJCC) (2009) stage IV cutaneous melanoma or stage III cutaneous or acral melanoma that is judged inoperable; patients with a history of uveal or mucosal melanoma are not eligible Histologic or cytologic diagnosis of cutaneous melanoma that is considered unresectable (stage III) or metastatic (stage IV); ocular and mucosal melanoma is excluded Unresectable Stage III or Stage IV melanoma. All patients must be either stage IIIb/c or stage IV melanoma according to the American Joint Committee on Cancer (AJCC) (7th edition) and have histologically confirmed melanoma that is felt to be surgically unresectable in order to be eligible\r\n* All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible\r\n* Patients must not have received prior anticancer treatment for metastatic disease (for example, but not limited to, systemic, local, radiation, radiopharmaceutical)\r\n* Exceptions: Surgery for melanoma and/or post-resection brain radiotherapy (RT) if central nervous system (CNS) metastases and/or prior treatment with adjuvant IFN\r\n* All patients must have their disease status documented by a complete physical examination and imaging studies within 4 weeks prior to the first dose of study drug; imaging studies must include computerized tomography (CT) scan of neck, chest, abdomen, pelvis, and all known sites of resected disease in the setting of stage IIIb/c or stage IV disease, and brain magnetic resonance imaging ([MRI], brain CT allowable if MRI is contraindicated)\r\n* The complete set of baseline radiographic images must be available before treatment initiation Participants must have histologically confirmed Stage III (unresectable) or Stage IV melanoma, per the AJCC staging system Patients with histologically confirmed unresectable stage III or stage IV metastatic melanoma, who have not been previously treated with a SEMA4D antibody and have had prior anti-PD1/PDL1 inhibitors with documented progression; patient may have or not have prior anti-CTLA4 treatments Participants must be newly diagnosed, treatment-naive with histologically confirmed stage IIIC unresectable melanoma or stage IV melanoma Have a histologically or cytologically confirmed diagnosis of unresectable stage III or IV melanoma; patient may not have a diagnosis of uveal or mucosal melanoma Histologically or cytologically confirmed diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to curative local therapy Have unresectable (stage III) or advanced (stage IV) melanoma Have unresectable stage III or stage IV melanoma Histologically or cytologically confirmed malignant melanoma at Screeningthat is unresectable/unresected Stage IIIB, IIIC, IIID or IV. Patients with unresectable mucosal melanoma may be enrolled after consultation with the Medical Monitor. Patients must have received and failed or refused available therapy for unresectable/unresected Stage III or IV melanoma. Diagnosis of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy Histologic or cytologic confirmation of unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy Failure to confirm histologically or cytologically unresectable stage III or metastatic melanoma (stage IV) not amenable to local therapy Subjects who are ipilimumab naive with progressive unresectable stage III or stage IV melanoma; eligible patients may have had prior adjuvant therapy, but not including ipilimumab, and been treated with up to 3 prior treatments for metastatic melanoma (eg, chemotherapy, other biologic or targeted therapy or IL-2) Histologic or cytologic confirmation of stage III or stage IV melanoma Patients who have unresectable stage III through stage IV metastatic melanoma that have not received prior PD-1 directed therapy (Arm A) or that have progressed despite prior PD-1 directed therapy (Arm B) CAPMATINIB INCLUSION CRITERIA: Unresectable stage III or stage IV melanoma by clinical or radiographic criteria CERITINIB INCLUSION CRITERIA: Unresectable stage III or stage IV melanoma by clinical or radiographic criteria REGORAFENIB INCLUSION CRITERIA: Unresectable stage III or stage IV melanoma by clinical or radiographic criteria ENTRECTINIB INCLUSION CRITERIA: Unresectable stage III or stage IV melanoma by clinical or radiographic criteria Subjects with metastatic or unresectable stage IIIb/c of IV melanoma for whom treatment with pembrolizumab is indicated and who have at least one cutaneous, subcutaneous tumor or palpable lymph node amenable to intratumoral injection. AJCC stage III or IV completely resectable melanoma identified before surgery Patients with metastatic, surgically unresectable melanoma or newly diagnosed melanoma patients of any stage unable to receive or complete standard therapy The subject must have clinical stage III or resectable stage IV MEL; subject’s may not have a diagnosis of uveal or mucosal melanoma Patient must have a histologically or cytologically confirmed diagnosis of unresectable stage III or IV melanoma; patient may not have a diagnosis of uveal melanoma Histological/cytological diagnosis of melanoma. AJCC stage IV (any T, any N, M1), metastatic, progressive, refractory, melanoma. Patients with stage IB or II cutaneous melanoma A history of AJCC stage IIIB/C or stage IV melanoma but no current clinical evidence of metastatic disease Participants must have histologically confirmed unresectable stage III or stage IV melanoma Treatment of unresectable stage III or stage IV melanoma with a tyrosine kinase inhibitor within prior 4 months; sorafenib for purposes of eligibility will not be considered acceptable prior therapy More than 3 prior systemic therapies for unresectable stage III or stage IV melanoma Histologically confirmed locally advanced unresectable (stage III) or stage IV pancreatic ductal adenocarcinoma (PDAC) Patients must have unresectable stage III or stage IV melanoma; patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive Diagnosis of stage IV melanoma Melanoma cohort only: histologic proof of surgically unresectable stage IV malignant melanoma Pathologically confirmed, clinically evident (by physical examination or radiographic imaging) stage IIIB, IIIC, and IV M1a and b cutaneous melanoma (anatomic stages T1-4b N1a and T1-4b N2a not included); the current diagnosis may be the patient’s first diagnosis of melanoma or recurrent melanoma after previous diagnosis of an earlier stage melanoma Histologic or cytologic diagnosis of cutaneous melanoma, mucosal melanoma, or melanoma of unknown primary that is considered unresectable (stage III) or metastatic (stage IV) Patients must have primary cutaneous melanoma that belong to one of the following American Joint Commission on Cancer (AJCC) stages (2009 AJCC Melanoma Staging System):\r\n* Stage IIIB\r\n** T1-4b N1a M0\r\n** T1-4b N2a M0\r\n** T1-4b N1b M0\r\n** T1-4b N2b M0\r\n** T1-4b N2c M0\r\n* Stage IIIC\r\n** T1-4b N1b M0\r\n** T1-4b N2b M0\r\n** T1-4b N2c M0\r\n** Any T N3 M0\r\n* Stage IV \r\n** M1a\r\n** M1b\r\n** NOTE: patients with stage IV melanoma must have normal lactate dehydrogenase (LDH) and either distant skin, subcutaneous, lymph node, or lung metastases, but no other visceral metastases in order to be eligible; for patients with resected stage IV melanoma, LDH within the institutional upper limit of normal (ULN) must be documented within 4 weeks prior to randomization Unresectable stage III or IV validated by clinical criteria (including recurrent melanoma), or patients with multiple skin/soft tissue metastases of melanoma that may be resectable but are judged to have a future recurrence risk exceeding 70% (e.g., large adenopathy, distant skin metastases or multiple in-transit melanoma metastases); tumor deemed amenable to biopsy (excisional, incisional, or core, with at least 100 mm^3 tumor volume per biopsy date) and fine-needle aspiration (FNA) biopsy\r\n* NOTE: optimally, patients will have tumor approachable for three serial biopsies during the trial; for patients with only one or two tumors approachable for biopsy, available tumor blocks from prior biopsies can serve as the pretreatment sample, but only if formalin-fixed tumor tissue is available and adequate to provide at least 20 unstained slides with sufficient tumor for analysis\r\n* NOTE: patients with unresectable advanced stage III or IV melanoma (including recurrent melanoma) are only eligible if they have failed at least one other first-line systemic therapy (other than adjuvant therapy); exceptions to this requirement are those patients who have refused and/or are ineligible for other systemic therapies\r\n* NOTE: v-raf murine sarcoma viral oncogene homolog B inhibitor (BRAFi) should be considered for all ‘unresectable” or metastatic melanoma with BRAFV600E mutation; for low burden in-transit disease patients may enter trial without prior systemic therapy\r\n** Stage IV no evidence of disease (NED) is excluded by this criterion Patients must have unresectable stage III or stage IV melanoma, either initial presentation or recurrent, that is of cutaneous origin or unknown primary origin and that is histologically diagnosed Patients must have unresectable metastatic stage IV melanoma or stage III intransit or regional nodal disease, and in the opinion of the institutional Principal Investigator (PI) is an acceptable candidate for ACT with high dose IL-2 (aldesleukin) Patients must have unresectable metastatic stage IV melanoma or stage III in-transit or regional nodal disease and in the opinion of the principal investigator (PI) or treating co-investigator is an acceptable candidate for ACT Histologic diagnosis of unresectable stage III or IV melanoma\r\n* All melanomas regardless of primary site of disease will be allowed Completely surgically resected stage IIIb/c/d or stage IV melanoma within 12 weeks of participation in study. Patients must have advanced (stage III-IV) or recurrent histologically confirmed USPC Have unresectable Stage III or Stage IV melanoma, as per AJCC staging system not amenable to local therapy Have advanced, unresectable (Stage III) or metastatic (Stage IV) melanoma; Histologically-confirmed (1) NSCLC, (2) bladder cancer, (3) castrate-resistant prostate cancer which are metastatic, or (4) stage 3C or stage 4 melanoma. Untreated or previously received one treatment regimen for measurable unresectable stage III or stage IV melanoma (American Joint Committee on Cancer [AJCC] 2010) (for BRAF wild-type, and regardless of human leukocyte antigen [HLA] type); untreated or previously received up to two treatment regimens for measurable unresectable stage III or stage IV melanoma (AJCC 2010) (for BRAF mutant, and regardless of HLA type; If 2 prior regimens, one should be a BRAF inhibitor); this does not include any therapies given in the adjuvant setting Unresectable Stage III or Stage IV melanoma (AJCC 2010) Subjects who are ipilimumab naïve with progressive unresectable stage III or stage IV melanoma who are either treatment naïve or may have been treated with up to 3 prior treatments for melanoma (e.g. chemotherapy, biologic or targeted therapy or interleukin [IL]-2) Histologic or cytologic confirmation of stage III or stage IV melanoma Stage IV melanoma or stage III melanoma that is unlikely to be cured by surgery Participants with BRAFV600 mutation-positive, cutaneous melanoma (either pathologic Stage IIC or Stage III according to AJCC Staging Criteria version 7 that has been completely resected Histologically confirmed Stage IIb, IIc, III melanoma Histologically confirmed melanoma that is considered surgically incurable with either: \r\n* Stage IIIc melanoma including locally relapsed, satellite, in-transit lesions or bulky draining node metastasis\r\n* Stage IV melanoma (M1a, M1b, or M1c) Histologic diagnosis of unresectable III or stage IV metastatic melanoma The patient must have a pathologically confirmed (by histology or cytology) diagnosis of melanoma, which is currently Stage 3 (unresectable) or Stage 4 disease. Patients must have histologically confirmed metastatic melanoma with measurable, stage III (lymph node or in transit lesions) or stage IVA, IVB, or IVC disease. Naive or any number of prior systemic therapeutic regimens for unresectable stage III or stage IV melanoma, except prior BRAF or MEK inhibitor agents; this includes chemotherapy, immunotherapy, biochemotherapy, or investigational treatments; patients may also have received therapies in the adjuvant setting Patients must have histologically or cytologically confirmed stage IIIB/C or stage IV oligometastatic melanoma; oligometastatic melanoma is defined as three or fewer areas of resectable disease excluding central nervous system and bone involvement; patients with cutaneous, mucosal, acral, ocular or unknown primary melanomas are eligible for enrollment; for patients with stage IV disease with distant lymph nodes (stage M1a), a maximum of three separate lymph node sites fit the definition of oligometastatic disease; resectable tumors are defined as having no significant vascular, neural or bony involvement; only cases where a complete surgical resection with tumor-free margins can safely be achieved are defined as resectable Subject with stage IIIB to IVM1c melanoma for whom surgery is not recommended Completely resected Stage III melanoma Patients must have Stage IIIB, IIIC or IV melanoma, which is unresectable/unresected or histologically confirmed diagnosis of metastatic malignant melanoma. Histologic or cytologic proof of surgically unresectable stage IV malignant melanoma - including that of uveal and mucosal origin\r\n* Note: biopsy can be of locoregional disease in setting of clinically evident stage IV disease; a biopsy of the primary tumor alone does not fulfill this requirement Diagnosis of locally advanced, unresectable or metastatic cutaneous melanoma or unknown primary melanoma (AJCC Stage IIIB, IIIC, or IV) Patients must have histologically confirmed melanoma with BRAF^V600 mutation; patients must have stage IIIC or stage IV disease Histologically confirmed stage III (unresectable) or stage IV melanoma Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III mucosal or cutaneous melanoma are eligible Diagnosis of locally advanced, unresectable or metastatic cutaneous or melanoma of unknown primary AJCC Stage IIIC or IV (uveal and mucosal melanoma are excluded) Unresectable stage III/IV melanoma Histologically confirmed Stage III (unresectable)/Stage IV melanoma Patients with a history of stage III melanoma (any primary melanoma with locoregional nodal/subcutaneous disease) treated with surgical resection who subsequently have disease recurrence meeting the criteria for stage IIIC disease Completely resected histologically confirmed high-risk [Stage IIIa (LN metastasis more than 1 mm), IIIb or IIIc cutaneous melanoma determined to be V600E/K mutation positive by a central laboratory. Patients presenting with initial resectable lymph node recurrence after a diagnosis of Stage I or II melanoma are eligible. Stage IIIc or Stage IV BRAF V600E/K cutaneous melanoma Histologically confirmed stage IV melanoma including brain metastasis Patients must have histologically or cytologically confirmed melanoma stage III/IV, unresectable Histologic/cytologic proof of stage IV malignant melanoma not amenable to surgery For Melanoma Subjects: Have histologically or cytologically confirmed diagnosis of unresectable Stage III or metastatic (Stage IV) melanoma not amenable to local therapy, and irrespective of PD-L1 status Complete and adequate resection of Stage III melanoma with histologically confirmed melanoma metastatic to lymph node Unresectable stage lll or IV, histologically confirmed diagnosis of one of the following solid tumors: Patient must have histologically or cytologically confirmed diagnosis of stage III melanoma inoperable/not amenable to local treatment or stage IV melanoma. Unresectable Stage III or IV disease Histologically confirmed surgically incurable and unresectable Stage IIIC or Stage IV (AJCC) melanoma Patients with histologically documented diagnosis of advanced stage IV or unresectable stage III melanoma are eligible Patients must have a histologically confirmed diagnosis (by either primary surgical specimen or biopsy for recurrence) of advanced stage (stage III or IV) or recurrent endometrioid endometrial cancer Patients with histologically proven melanoma with metastasis that is unresectable Stage III or Stage IV. This will include bulky stage III and M1-3. Patients with melanoma with documented metastases to the brain are eligible. Previously treated or untreated, unresectable Stage III or Stage IV malignant melanoma Histologically or cytologically documented advanced NSCLC who have Stage IIIB/Stage IV disease, or recurrent disease following radiation therapy or surgical resection or advanced, unresectable (Stage III) or metastatic (Stage IV) melanoma; Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic) and determined to be BRAF V600E or V600K mutation-positive (cohort A) or mutation-negative (cohorts B and C) Patients must have histologically confirmed recurrent stage III or stage IV melanoma (AJCC 7th edition classification); cutaneous melanoma, ocular or mucosal melanoma will be eligible Histologically confirmed stage IV or unresectable stage III melanoma with documented BRAF V600 mutation Histologically confirmed cutaneous melanoma that is either Stage IIIc (unresectable) or Stage IV (metastatic), and determined to be BRAF V600E or V600K mutation-positive by the local laboratory. Subjects with ocular or mucosal melanoma are not eligible Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma metastases (i.e., AJCC Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases) Unresectable Stage III or Stage IV melanoma Histologic diagnosis of melanoma with in transit metastasis stage IIIB, IIIC, or IV Unresectable stage III or stage IV M1a/M1b/M1c melanoma including patients with uveal melanoma Histologic diagnosis of unresectable stage IIIC or stage IV melanoma that is BRAF V600 mutation positive Patients must have pathologically confirmed stage IV or unresectable stage III melanoma; patients must not have disease that is suitable for local therapy, administered with curative intent Phase I: Diagnosis of primary pathologic stage 0–III cutaneous malignant melanoma Phase II: Diagnosis of primary pathologic stage 0–III cutaneous malignant melanoma Have been diagnosed within one month with a pathologically confirmed advanced cancer who have an average of < 2 year (y) life expectancy (primary stage IV hepatobiliary, esophageal, colorectal, glioblastoma, gastric, pancreatic, melanoma, head and neck, or stage III or IV lung or pancreatic cancers) and are being treated at one of the participating hospital sites and speak English or Spanish Participants must have histologically confirmed malignancy that is metastatic or currently unresectable; eligible malignancies include:\r\n* Adenocarcinoma of the pancreas (locally advanced or metastatic)\r\n* Colorectal (stage IV)\r\n* Non-small cell lung cancer (currently unresectable stage III or stage IV) Patients must have histologically or cytologically confirmed diagnosis of unresectable, stage III or metastatic melanoma Melanoma tumor that meets indications for a groin SLN biopsy with a >= 10% risk of having metastasis to the draining lymph node (i.e. stage IB to stage IIIC melanoma of the lower body below the umbilicus) Subjects must be diagnosed with histologically proven stage IV (metastatic) melanoma or stage III with bulky disease which may or may not be amenable for surgery and are receiving therapy at present Subjects with unresectable Stage III or IV melanoma who are either refractory or intolerant to, or have refused standard therapy for treatment of metastatic melanoma