Genetic Analysis in Understanding Immunotherapy Resistance in Patients with Stage III-IV Melanoma

Inclusion Criteria

• ARM I: Patients with stage III or IV melanoma, with melanoma validated by histology or cytology
• ARM I: Patients may participate with primary cutaneous melanomas of unknown primary site
• ARM I: Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
• ARM I: Life expectancy of at least 6 months
• ARM I: Patients with active disease will be treated with either an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody (combined therapy regimens with any other agents are not allowed on this study)
• ARM I: Patient must have a measurable systemic lesion defined as greater than or equal to 10 mm based on PET CT/CT/MRI imaging; pretreatment PET CT/CT imaging must be performed =< 42 days prior to treatment initiation
• ARM I: Patients with target skin lesions must equal at least 10 mm when their longest diameters are aggregated; target skin lesions (5 maximum) must be at least 5 mm in their longest diameter to be considered measurable by caliper or ruler
• ARM I: Those patients with a failed biopsy attempt or those with disease that is not amenable to biopsy will still be eligible for enrollment and will only undergo blood draws during the study protocol. Likewise, if an initial blood draw is not feasible, patients will still be eligible for enrollment if only tissue is obtained
• ARM I: Both men and women of all races and ethnic groups are eligible for this trial
• ARM I: Ability to understand and the willingness to sign a written informed consent document
• ARM I: Patients with intra-cranial disease or disease involving the central nervous system are eligible
• ARM II: Patients with a current diagnosis of stage III or IV melanoma or a history of stage III or IV melanoma, with melanoma validated by histology or cytology
• ARM II: ECOG performance status of 0-2
• ARM II: Patients selected for future adjuvant anti-PD-1 antibody immunotherapy following resection of stage III or stage IV melanoma or patients who received prior adjuvant anti-PD-1 antibody immunotherapy for stage III or IV melanoma and have developed recurrent disease based on physical exam and/or CT/PET CT cross-sectional imaging
• ARM II: Those patients with a failed biopsy attempt or those with disease that is not amenable to biopsy will still be eligible for enrollment and will only undergo blood draws during the study protocol; of note, any tissue subjected to prior adjuvant radiation therapy will not be considered for further tissue sampling on this protocol. Likewise, if an initial blood draw is not feasible, patients will still be eligible for enrollment if only tissue is obtained. Of note, any tissue subjected to prior adjuvant radiation therapy will not be considered for further tissue sampling on this protocol
• ARM II: Both men and women of all races and ethnic groups are eligible for this trial
• ARM II: Ability to understand and the willingness to sign a written informed consent document
• ARM II: Patients with intra-cranial disease or disease involving the central nervous system are eligible
• RETROSPECTIVE SUBJECT SELECTION: Patients with stage III or IV melanoma, with melanoma validated by histology or cytology
• RETROSPECTIVE SUBJECT SELECTION: Patients with primary cutaneous melanomas of unknown primary site are eligible
• RETROSPECTIVE SUBJECT SELECTION: Patients were treated with either an anti-CTLA-4 antibody, an anti-PD-1 antibody, an anti-PD-L1 antibody, or a combination of an anti-CTLA-4 antibody/anti-PD-1 antibody (combined therapy regimens with any other agents are not allowed)
• RETROSPECTIVE SUBJECT SELECTION: Both men and women of all races and ethnic groups are eligible for this trial
• RETROSPECTIVE SUBJECT SELECTION: Patients with intra-cranial disease or disease involving the central nervous system are eligible

Exclusion Criteria

• ARM I: Patients with a history of a systemic autoimmune disease (e.g. systemic lupus erythematosus) requiring active therapy
• ARM I: Patients with a history of another malignancy within the last 5 years except for those patients felt by the treating physician to be cured of that malignancy
• ARM I: Patients with a diagnosis of a mucosal or ocular melanoma
• ARM I: Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who have had prior cytotoxic chemotherapy if less than 6 weeks prior to day of initial biopsy
• ARM I: Patients who have had prior interferon therapy if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who have had prior anti-CTLA-4 antibody or anti-PD-1 antibody or anti-PD-L1 antibody therapy if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who have had prior IL-2 therapy if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who have had prior BRAF inhibitor and/or MEK inhibitor therapy if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who have received an immunotherapy agent on a previous clinical trial protocol if less than 4 weeks prior to day of initial biopsy
• ARM I: Patients who are undergoing active steroid therapy if the dose exceeds physiologic steroid doses (equivalent of prednisone 10 mg orally [p.o.] daily or less)
• ARM I: Patients with ongoing or active infection
• ARM I: Pregnant patients
• ARM I: Patients with any laboratory test values or serious pre-existing medical condition, that in the opinion of the investigator, makes the patient unsuitable for the study
• ARM I: Patients unable to comply with the requirements of the study protocol
• ARM II: Patients with a history of a systemic autoimmune disease (e.g. systemic lupus erythematosus) requiring active therapy
• ARM II: Patients with a history of another malignancy within the last 5 years except for those patients felt by the treating physician to be cured of that malignancy
• ARM II: Patients with a diagnosis of a mucosal or ocular melanoma
• ARM II: Patients who have had prior cytotoxic chemotherapy if less than 6 weeks prior to day of initial biopsy
• ARM II: Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who have had prior interferon therapy if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who have had prior anti-CTLA-4 antibody or anti-PD-1 antibody or anti-PD-L1 antibody therapy if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who have had prior IL-2 therapy if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who have had prior BRAF inhibitor and/or MEK inhibitor therapy if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who have received an immunotherapy agent on a previous clinical trial protocol if less than 4 weeks prior to day of initial biopsy
• ARM II: Patients who are undergoing active steroid therapy if the dose exceeds physiologic steroid doses (equivalent of prednisone 10 mg p.o. daily or less)
• ARM II: Patients with ongoing or active infection
• ARM II: Pregnant patients
• ARM II: Patients with any laboratory test values or serious pre-existing medical condition, that in the opinion of the investigator, makes the patient unsuitable for the study
• ARM II: Patients unable to comply with the requirements of the study protocol
• RETROSPECTIVE SUBJECT SELECTION: Patients with a history of a systemic autoimmune disease (eg systemic lupus erythematosus) requiring active therapy
• RETROSPECTIVE SUBJECT SELECTION: Patients with a history of another malignancy within the 5 years prior to initiating treatment except for those patients felt by the treating physician to be cured of that malignancy at that time
• RETROSPECTIVE SUBJECT SELECTION: Patients with a diagnosis of a mucosal or ocular melanoma
• RETROSPECTIVE SUBJECT SELECTION: Patients who have undergone adjuvant locoregional radiation therapy if less than 4 weeks prior to biopsy or surgery
• RETROSPECTIVE SUBJECT SELECTION: Patients who had prior cytotoxic chemotherapy if less than 6 weeks prior to biopsy or surgery
• RETROSPECTIVE SUBJECT SELECTION: Patients who received any systemic cancer therapy if less than 4 weeks prior to biopsy or surgery
• RETROSPECTIVE SUBJECT SELECTION: Patients who were undergoing active steroid therapy if the dose exceeds physiologic steroid doses (equivalent of prednisone 10 mg po daily or less) at the time of initiating immunotherapy
• RETROSPECTIVE SUBJECT SELECTION: Patients with ongoing or active infection at the time of initiating immunotherapy
• RETROSPECTIVE SUBJECT SELECTION: Pregnant patients
• RETROSPECTIVE SUBJECT SELECTION: Patients with any laboratory test values or serious pre-existing medical condition, that in the opinion of the investigator, made the patient unsuitable for the study