Patients must have histological or cytological confirmation of melanoma that is metastatic or unresectable and clearly progressive\r\n* NOTE: Any patient with BRAF V600 mutant melanoma (whether cutaneous, acral or mucosal primary) who meets the eligibility criteria is eligible for participation in this trial; patients with uveal melanoma are not eligible for this trial
Patients with ocular melanoma.
Ocular melanoma.
Ocular melanoma
Ocular melanoma
Uveal melanoma is excluded
Histopathologically confirmed diagnosis of metastatic or unresectable uveal melanoma or non-uveal melanoma harboring a GNAQ or GNA11 mutation; Note: For subjects with a diagnosis of uveal melanoma, documentation of mutation status for uveal melanoma will not be required prospectively given the high rate of GNAQ/11 mutations (> 90%) in this population
Melanoma (excluding uveal melanoma);
Subjects with melanoma or with a history of melanoma, invasive squamous cell carcinomas, or aphakia (due to contraindication for use of methoxsalen).
Patients with melanoma of cutaneous, mucosal or acral-lentiginous origin or of unknown primary
Melanoma
Has Ocular Melanoma
Patients with uveal melanoma will not be eligible as these tumors show low expression of GD3
Patients with ocular, mucosal and unknown primary melanoma will also be eligible
History of uveal melanoma
Metastatic melanoma eligible for {or currently o
Rapidly progressing multi-focal metastatic melanoma
Melanoma
Study subjects previously treated with one of the peptides used in this trial, melanoma protein vaccine, melanoma whole cell vaccines, or with Montanide are not eligible
Patients with primary ocular or mucosal melanoma are excluded
Patients with melanoma arising from uveal/ocular primary sites.
Prior melanoma vaccinations may be an exclusion criterion in the following circumstances:\r\n* Patients who have received, within the prior 5 years, melanoma vaccines or other vaccines containing an incomplete Freund’s adjuvant (IFA; such as montanide ISA-51).\r\n* Patients who have received any melanoma vaccine within the past 12 months.\r\n* Patients who have been vaccinated in the past with any of the melanoma peptides in the LPV7 vaccine included in this study.
Patients must have a diagnosis of metastatic melanoma which is measurable either clinically or radiologically
Patients with carcinomatosis meningitis or a history of ocular/uveal melanoma are excluded
Phase 2 Cohort: ocular melanoma
Participants must not have ocular melanoma
Patients must have completely resected (as per standard of care) melanoma of cutaneous origin in order to be eligible for this study; patients must be classified as stage IIB or IIC cutaneous melanoma using the American Joint Committee on Cancer eighth edition; patients with melanoma of mucosal or other non-cutaneous origin are not eligible; patients with melanoma of ocular origin are not eligible
Ocular melanoma
Patients whose primary diagnosis was ocular melanoma
Diagnosis of choroidal melanoma
Melanoma located on face or digits
Histologic diagnosis of metastatic uveal melanoma.
Histologically or cytologically confirmed malignant melanoma from skin, or mucosal melanoma (i.e. ocular melanoma subjects are not eligible)
Patients must have unresectable cutaneous, mucosal or ocular metastatic stage III/IV melanoma, and in the opinion of the institutional principal investigator (PI) is an acceptable candidate for adoptive cell therapy (ACT) with high dose interleukin-2 (IL-2); patients with ocular or mucosal metastatic melanoma may be included, as our prior experience indicates that TIL can be successfully propagated from these subtypes of melanoma metastases
CAPMATINIB EXCLUSION CRITERIA: Uveal melanoma
ENTRECTINIB EXCLUSION CRITERIA: Uveal melanoma
Inclusion criteria Part 1: Safety run-in\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN\n\n          -  ECOG performance status ? 1\n\n        Part 2: Biomarker cohort\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection\n\n          -  ECOG performance status ? 2\n\n        Part 3: Double-blind, randomized, placebo-controlled part\n\n          -  Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation\n\n          -  ECOG performance status ? 2\n\n        Exclusion Criteria:\n\n        Part 1: Safety run-in\n\n          -  Subjects with uveal or mucosal melanoma\n\n          -  Any history of CNS metastases\n\n          -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma\n\n          -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6\n             month\n\n          -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months\n\n          -  Radiation therapy within 4 weeks prior to start of study treatment\n\n          -  Active, known, suspected or a documented history of autoimmune disease\n\n        Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part\n\n          -  Subjects with uveal or mucosal melanoma\n\n          -  Clinically active cerebral melanoma metastasis\n\n          -  Prior systemic anti-cancer treatment for unresectable or metastatic melanoma\n\n          -  Prior loco-regional treatment for unresectable or metastatic melanoma in the last 6\n             month\n\n          -  Prior neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months\n\n          -  Radiation therapy within 4 weeks prior to start of study treatment\n\n          -  Active, known, suspected or a documented history of autoimmune disease\n\n        Other protocol-defined Inclusion/Exclusion may apply.
Histologically-confirmed primary uveal melanoma
Metastatic uveal melanoma
Histologic diagnosis of melanoma
Ocular melanoma
Metastatic uveal melanoma patients with bone-only disease
50% or less histologically or cytologically-proven ocular melanoma metastases in the parenchyma of the liver.
Patients with advanced melanoma defined as unresectable stage III or metastatic stage IV disease. Patients with acral or mucosal melanoma or patients with unknown primary melanoma are acceptable in Phase 1b but are excluded from Phase II. Patients with uveal melanoma are excluded from the study.
Patients must have metastatic melanoma, uveal melanoma or stage III in-transit or regional nodal disease (Turnstile I)
Histologic diagnosis of stage IV metastatic melanoma, with 1 melanoma lesion that can be safely irradiated in the opinion of the radiation oncologist (note: subjects with primary ocular and mucosal melanoma are permitted). Lesions may include, but are not limited to:
Melanoma of ocular primary
Patient with detectable c-kit JM mutation confirmed by DNA or RNA sequencing, which is expected to be mainly found after screening of mucosal or acral melanoma or melanoma on skin with chronic sun-induced damages (defined by a microscopically marked elastosis involving the skin surrounding their primary melanoma)
Measurable metastatic uveal melanoma
Histologic diagnosis of metastatic melanoma
Patients with uveal/ocular melanoma are excluded
Histologically confirmed melanoma of cutaneous primary; metastatic melanoma from unknown primary are allowed
Patients with melanoma of mucosal or ocular primary
Mucosal melanoma and uveal melanoma are not allowed
Has primary ocular melanoma
Histologically or cytologically confirmed uveal melanoma that is metastatic or unresectable; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of diagnosis will be performed at the participating site
Measurable metastatic ocular melanoma
No prior anti-cancer treatment for melanoma (except surgery for the melanoma lesion(s) and/or except for adjuvant radiation therapy (RT) after neurosurgical resection for central nervous system (CNS) lesions)
History of uveal melanoma
Subjects must not have primary uveal or mucosal melanoma, history or evidence of melanoma associated with immunodeficiency states or history of other malignancy within the past 3 years.
For Phase 2 expansion cohorts: Subjects with NSCLC, melanoma (checkpoint inhibitor naïve, primary refractory melanoma, relapsed melanoma), transitional cell carcinoma of the GU tract, SCCHN, ovarian cancer, MSI high CRC, RCC, DLBCL, and TNBC.
Ocular melanoma is excluded.
Patients must have completely resected melanoma of cutaneous origin or of unknown primary in order to be eligible for this study; patients must be classified as stage IIIA (N2a), IIIB, IIIC, or stage IV melanoma; patients with non-ulcerated T1b N1a disease are not eligible; patients with melanoma of mucosal or other non-cutaneous origin are eligible; patients with melanoma of ocular origin are not eligible; patients with a history of brain metastases are ineligible
For melanoma: Uveal melanoma or LDH >1.1 x ULN
Subjects with melanoma:
Subject must not have primary ocular or mucosal melanoma, or history or evidence of melanoma associated with immunodeficiency states (eg, hereditary immune deficiency, organ transplant, or leukemia).
Patients are excluded if they have known involvement of melanoma within the gastrointestinal tract
Histologic or cytologic documentation of metastatic or Stage IIIc unresectable melanoma, with BRAFV600 mutation as assessed by BRAFV600 Mutation Test. Origin of the primary tumor may be of skin, mucosal, or acral locations but not of uveal origin. Participants having an unknown primary tumor may be eligible if uveal melanoma can be ruled out
Uveal or ocular melanoma
Ocular or uveal melanoma
Subjects with ocular melanoma
Histologically or cytologically confirmed diagnosis of unresectable or metastatic malignant melanoma, including cutaneous, ocular, mucosal and unknown primary tumour.
Prior adjuvant melanoma therapy is permitted; any number of previous treatments for melanoma is permitted.
Uveal or ocular MEL
Patients must have measurable metastatic melanoma
Primary uveal or mucosal melanoma
Diagnosis of non-cutaneous melanoma or melanoma with unknown primary origin
The patient has uveal melanoma.
Mucosal melanoma and uvueal melanoma.
Patients with ocular melanoma.
Eligibility for pheresis: (Turnstile 1) Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease. A diagnosis of uveal melanoma can be made clinically without primary tissue evaluation, based on history and records. A prior history of brachytherapy to the eye is sufficient clinical support for a diagnosis of uveal melanoma.
Patient has uveal melanoma
Patients diagnosed with advanced melanoma
Desmoplastic or neurotropic melanoma.
Subungual melanoma
Primary ocular or mucosal melanoma
Mucosal or ocular melanoma
Histologic confirmation of advanced (metastatic or unresectable) uveal melanoma; if uveal melanoma has been diagnosed clinically and/or by gene expression profiling, patients may be included following discussion with the principal investigator
Metastatic histologically or cytologically confirmed uveal melanoma with pathologic confirmation at a participating center that is judged to be progressive in the opinion of the treating physician; for the dose escalation portion of the trial only, patients with non-uveal melanoma harboring a GNAQ or GNA11 mutation will also be eligible
Histopathologic documentation of melanoma concurrent with the diagnosis of metastatic disease
Melanoma
Uveal and mucosal melanoma
Ocular melanoma
Patients with metastatic uveal melanoma
Group 4: Patients with NRAS mutated melanoma
Uveal or mucosal melanoma
Ocular melanoma
Known mucosal or ocular melanoma or the presence of unresectable in-transit metastases.
Prior systemic anti-cancer treatment and radiotherapy for melanoma; prior surgery for melanoma is allowed.
Patients must have metastatic histologically or cytologically confirmed uveal melanoma; (if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma); pathologic confirmation of diagnosis will be performed at Columbia University, Memorial Sloan-Kettering Cancer Center (MSKCC) or Vanderbilt University Medical Center
Measurable metastatic melanoma with available autologous TIL
Uveal melanoma with biopsy proven metastatic disease
Patients who have a diagnosis for which a PD-(L)-1 inhibitor has been approved must have previously received treatment with one of these therapies. a. Melanoma Dose Expansion: Patients must have histologically confirmed metastatic melanoma (ocular melanoma not included) which has progressed on or after treatment with a PD-(L)1 inhibitor.
Has a history of ocular melanoma
Histological or cytological confirmed melanoma that is metastatic or unresectable; patients must have measurable disease (at least one measurable lesion) as defined by Response Evaluation Criteria In Solid Tumors (RECIST) criteria; NOTE: all sites of disease must be evaluated within 4 weeks prior to registration to treatment; patients must have a history of melanoma of one of the following subtypes: \r\n* Acral (as defined as occurring on the palms, soles, or subungual sites)\r\n* Melanoma arising from the vagina and/or vulva\r\n* Melanoma arising on other mucosal surface (not vagina or vulva)
Patients must not have ocular melanoma
Prior therapy for melanoma except surgery
Histologic diagnosis of melanoma.
Ocular Melanoma
Melanoma of uveal origin
Patients must have histologically or cytologically confirmed metastatic or locally recurrent uveal melanoma; because histologic or cytologic confirmation of primary uveal melanoma is not always possible, confirmation of the clinical diagnosis of uveal melanoma by the treating investigator is allowed; clinical diagnosis of uveal melanoma is often made by an ophthalmologist, not by tissue diagnosis; if an ophthalmologist diagnosed and treated a patient for uveal melanoma in the past, it is sufficient for a clinical diagnosis
Primary Ocular Melanoma
All melanomas, except ocular/uveal melanoma, regardless of primary site of disease will be allowed; mucosal melanomas are eligible.
Patients with carcinomatosis meningitis or a history of ocular/uveal melanoma are excluded.
Clinical diagnosis of primary uveal melanoma involving the posterior uveal tract in the study eye
Planned enucleation or brachytherapy of the study eye due to uveal melanoma
Uveal melanoma in the study eye originating in the anterior uveal tract (iris)
Histologically or cytologically confirmed diagnosis of advanced or metastatic cutaneous melanoma that is determined to be BRAFV600 wild type and either NRAS wild type or NRAS mutation type. Note: Subjects with a melanoma of unknown primary origin may be allowed to enrol if all other types of melanoma (e.g., uveal, mucosal, or acral) can be reasonably ruled out.
Patients must have metastatic histologically or cytologically confirmed uveal melanoma; if histologic or cytologic confirmation of the primary is not available, confirmation of the primary diagnosis of uveal melanoma by the treating investigator can be clinically obtained, as per standard practice for uveal melanoma; pathologic confirmation of metastatic disease will be performed at Memorial Sloan Kettering (MSK) or at a participating site
Uveal Melanoma with liver metastasis
Part A2 & B (RCC, NSCLC, HCC, and uveal melanoma): Have measurable disease as defined by RECIST v1.1.
Patients must have histologically or cytologically confirmed metastatic uveal melanoma
Melanoma of ocular origin
Are at risk for melanoma due to having a first degree relative with a history of melanoma and/or at least 3 second or third degree relatives on the same side of the family with a history of melanoma and/or
AIMS 1 AND 2: Healthy individuals with pigmented lesions or a partially biopsied melanoma or cutaneous melanoma metastasis whose treatment plan includes excision
Patient must not have melanoma
Histopathologically confirmed diagnosis of metastatic or unresectable malignant melanoma arising from skin. Ocular melanoma subjects are not eligible.
Primary ocular or mucosal melanoma.