Please select the eligibility criteria that correspond to the clinical trial below.
Title: BRIM 3: A Randomized, Open-Label, Controlled, Multicenter, Phase III Study in Previously Untreated Patients With Unresectable Stage IIIC or Stage IV Melanoma With V600E BRAF Mutation Receiving Vemurafenib (RO5185426) or Dacarbazine
Brief Summary: This randomized, open-label study evaluated the efficacy, safety and tolerability of vemurafenib (RO5185426) as compared to dacarbazine in previously untreated patients with metastatic melanoma. Patients were randomized to receive either vemurafenib 960 mg orally twice daily or dacarbazine 1000 mg/m2 intravenously every 3 weeks. Study treatment was continued until disease progression or unacceptable toxicity occurred. The data and safety monitoring board recommended that patients in the dacarbazine group be allowed to cross over to receive vemurafenib, and the protocol was amended accordingly on January 14, 2011, as both overall survival and progression-free survival endpoints had met the prespecified criteria for statistical significance in favor of vemurafenib.


Options:
A: Inclusion Criteria:

* Participants with histologically confirmed melanoma, either unresectable stage IIIc or stage IV metastatic melanoma, as defined by the American Joint Committee on Cancer 7th edition. Unresectability of stage IIIc disease must have confirmation from a surgical oncologist
* Participants must be naïve to treatment for locally advanced unresectable or metastatic disease (ie, no prior systemic anti-cancer therapy for advanced disease; stage IIIc and IV). Prior adjuvant immunotherapy (including ipilimumab) is allowed
* Documentation of BRAF V600 mutation-positive status in melanoma tumor tissue (archival or newly obtained tumor samples) using the cobas 4800 BRAF V600 mutation test
* Measurable disease per RECIST v1.1
* Eastern Clinical Oncology Group performance status of 0 or 1
* Consent to provide archival for biomarker analyses
* Consent to undergo tumor biopsies for biomarker analyses
* Life expectancy greater than or equal to (≥) 12 weeks
* Adequate hematologic and end organ function

Exclusion Criteria:

* History of prior rapidly accelerated fibrosarcoma or mitogen-activated protein kinase pathway inhibitor treatment
* Palliative radiotherapy within 14 days prior to the first dose of study treatment
* Major surgery or traumatic injury within 14 days prior to first dose of study treatment
* Active malignancy other than melanoma that could potentially interfere with the interpretation of efficacy measures. Participants with a previous malignancy within the past 3 years are excluded except for participants with resected basal cell carcinoma or squamous cell carcinoma of the skin, melanoma in-situ, carcinoma in-situ of the cervix, and carcinoma in-situ of the breast
* History of or evidence of retinal pathology on ophthalmological examination that is considered a risk factor for neurosensory retinal detachment, retinal vein occlusion, or neovascular macular degeneration
* Uncontrolled glaucoma with intraocular pressure
* Serum cholesterol ≥ Grade 2
* Hypertriglyceridemia ≥ Grade 2
* Hyperglycemia (fasting) ≥ Grade 2
* History of clinically significant cardiac dysfunction
* Participants with active central nervous system (CNS) lesions (including carcinomatous meningitis) are excluded. However, participants are eligible if:

  1. All known CNS lesions have been treated with stereotactic therapy or surgery, AND
  2. There has been no evidence of clinical and radiographic disease progression in the CNS for ≥ 3 weeks after radiotherapy or surgery
* Current severe, uncontrolled systemic disease
* History of malabsorption or other condition that would interfere with absorption of study drugs
* Pregnant, lactating, or breast feeding women
B: Inclusion Criteria:

* adult patients \>/=18 years of age
* histologically confirmed metastatic melanoma (Stage IV, AJCC)
* patients must have completed and failed at least one prior standard of care regimen (e.g. DTIC, temozolomide, etc.)
* BRAF V600E positive mutation (by Roche CoDx BRAF mutation assay)
* measurable disease by RECIST criteria
* negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion

Exclusion Criteria:

* active CNS metastases on CT/MRI within 28 days prior to enrollment
* history of or known carcinomatous meningitis
* previous treatment with BRAF (sorafenib allowed) or MEK inhibitor
* cardiac dysrhythmias \>2 NCI CTCAE or treatment with drugs with dysrhythmic potential
* uncontrolled hypertension(\>150/100mmHg) despite optimal medical therapy
* infectious disease including HIV, HBV and HCV
C: Inclusion Criteria:

* adults, \>/=18 years of age
* metastatic melanoma, stage IIIC or IV (AJCC)
* treatment-naïve (no prior systemic anticancer therapy)
* positive for BRAF V600E mutation
* measurable disease by RECIST criteria
* negative pregnancy test and, for fertile men and women, effective contraception during treatment and for 6 months after completion

Exclusion Criteria:

* active central nervous system metastases
* history of carcinomatous meningitis
* severe cardiovascular disease within 6 months prior to study drug administration
* previous malignancy within 5 years prior to study, except for basal or squamous cell carcinoma of the skin, melanoma in-situ, or carcinoma in-situ of the cervix
D: Inclusion Criteria:

* written informed consent for the study
* ≥ 18 years of age
* histologically or cytologically confirmed diagnosis of cutaneous or unknown primary melanoma (excluding uveal/choroidal and mucosal melanoma; although acral melanoma is included) belonging to one of the following AJCC 8th edition TNM stages:

  1. Tx or T1-4 AND
  2. N1b, or N1c, or N2b, or N2c, or N3b, or N3c AND/OR
  3. M1a or M1b

Patients are eligible for this trial either at presentation for primary melanoma with concurrent regional nodal and/or in-transit metastasis and/or oligometastasis; AND/OR at the time of clinical detected nodal and/or in-transit and/or oligometastatic recurrence; and may belong to any of the following groups:

Primary melanoma with clinically apparent regional lymph node metastases; Clinically detected recurrent melanoma at the proximal regional lymph node(s) basin; Clinically detected primary melanoma involving multiple regional nodal groups; Clinical detected nodal melanoma (if single site) arising from an unknown primary; In-transit and/or satellite metastases with or without regional lymph node involvement; Distant skin and/or in-transit and/or satellite metastases with or without regional lymph node involvement; Oligometastatic lung disease with or without regional lymph node involved permitted if deemed resectable at baseline NOTE: Determination of resectability must be made at baseline to be eligible for this neoadjuvant study.

* measurable disease based on RECIST 1.1
* must provide tumor tissue from a newly obtained core, punch, incisional or excisional tumor biopsy
* 0 or 1 on the ECOG Performance Scale
* Demonstrate adequate organ function on screening labs obtained within 14 days of registration
* negative serum pregnancy test (females of childbearing potential)
* females of non-childbearing potential must be ≥45 years of age and has not had menses for \>1 year; if amenorrhoeic for \<2 years without history of a hysterectomy and oophorectomy must have an FSH value in the postmenopausal range; post-hysterectomy, post-bilateral oophorectomy, or post-tubal ligation (documented hysterectomy or oophorectomy)
* male subjects should agree to use an adequate method of contraception

Exclusion Criteria:

* Patients with uveal and/or mucosal melanoma histology are excluded (Patients with melanoma of unknown histology are permitted to enroll after discussion with Principal Investigator)
* Is currently participating in or has participated in a study of an investigational agent or using an investigational device within 4 weeks of the first dose of treatment.
* Is receiving systemic immunosuppression with either corticosteroids (\>10mg daily prednisone equivalent) or other immunosuppressive medications) for active autoimmune disease: history of active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids (\>10mg daily prednisone or equivalent) or systemic immunosuppressive agents
* ≥ CTCAE grade 3 immune-related AE (irAE) experienced with prior immunotherapy (except, non-clinically significant lab abnormalities (elevations in lipase, amylase not associated with clinically significant disease etc.) even if ≥ CTCAE grade 3 may enroll if resolved at this time, or, development of autoimmune disorders of Grade ≤ 3 may enroll if the disorder has resolved to Grade ≤ 1)
* received prior chemotherapy, targeted small molecule therapy, or radiation therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., ≤ Grade 1 or at baseline) from adverse events due to a previously administered agent (except ≤ Grade 2 neuropathy)
* autoimmune disorders of Grade 4 while on prior immunotherapy
* active (i.e., symptomatic or growing) central nervous system (CNS) and/or leptomeningeal metastases (CNS lesions that are treated and deemed stable (repeat imaging study done at least 2 weeks prior to first dose of study treatment) are NOT permitted to enroll even if other inclusion criteria are met and patients are neurologically asymptomatic)
* known additional malignancy that is progressing or requires active treatment (except, basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy)
* invasive cancer diagnosed and treated less than 2 years prior to current presentation (other indolent malignancies that are not progressing and/or deemed to require active therapy are not exclusionary)
* evidence of interstitial lung disease or active, non-infectious pneumonitis
* active infection requiring systemic therapy
* history or current evidence of any condition, therapy, or laboratory abnormality determined to be significant, in the opinion of the treating investigator
* known psychiatric or substance abuse disorders that would interfere with study compliance
* is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the trial
* had a live vaccine within 30 days of initiating protocol therapy
* received prior therapy with an IDO inhibitor, anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137 and/or combination (including nivolumab, pembrolizumab or ipilimumab/nivolumab). Prior treatment with ipilimumab or interferon alfa is allowed.
* history of allergic or hypersensitivity reaction to components or excipients of Dostarlimab (TSR-042) and TSR-022, interferon alfa or ipilimumab
* known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
* known history of or screening test that is positive for hepatitis B virus (HBV; eg, HBsAg reactive or HBV DNA detected) or hepatitis C virus (HCV; HCV antibody positive and/or HCV RNA quantitative is detected). Hepatitis C antibody - positive subjects who received and completed treatment for hepatitis C that was intended to eradicate the virus may participate if hepatitis C RNA levels are undetectable. Hepatitis B positive subjects who received and completed treatment for hepatitis B that was intended to eradicate the virus may participate if hepatitis B DNA levels are undetectable.

Answer: C