A Trial to Evaluate CSF ctDNA and Safety of Plixorafenib Alone or With Retifanlimab in Patients With BRAF-altered Glioma

Inclusion Arm A Only: * Patient must have received prior BRAF and/or MEK inhibitor therapy. 1. Prior RAF dimer disruptor or pan-RAF inhibitor not allowed 2. Prior immunotherapy allowed * The following intervals from previous treatments should have elapsed prior to enrollment: a. BRAFi/MEKi should be stopped 2 weeks prior to surgery * Patients must be maintained on a stable or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. No maximum dose. Topical and inhaled steroid treatment is allowed. Inclusion Arm B Only: * Patient must have received prior BRAF and/or MEK inhibitor therapy. 1. Prior RAF dimer disruptor or pan-RAF inhibitor allowed, 2. Prior immunotherapy not allowed (anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-CTLA-4 antibody or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathway). * The following intervals from previous treatments should have elapsed prior to first infusion: a. BRAFi/MEKi should be stopped 7 days prior to first retifanlimab infusion and at least 2 weeks prior to surgery. * Patients must be maintained on a stable (\<4mg daily dexamethasone) or decreasing dose of systemic corticosteroid regimen (no increase for 5 days) prior to screening MRI. Topical and inhaled steroid treatment is allowed. Inclusion Both Arms: * Histologic diagnosis of a primary CNS tumor with documented BRAF-V600E mutation by a CLIA approved DNA or RNA-based sequencing test (NGS or RNAseq). Immunohistochemistry alone is insufficient. * Karnofsky performance status ≥ 70. * Patient is 18 years of age or older. * Measurable disease by RANO 2.0 criteria on screening MRI. Leptomeningeal disease allowed. * Willing to submit archival tumor sample if available. * The following intervals from previous treatments should have elapsed prior to either day of surgery (for Arm A) or first infusion of Retifanlimab (for Arm B): * 12 weeks from the completion of radiation. * 8 weeks from an anti-VEGF therapy * 4 weeks from a nitrosourea chemotherapy * 2 weeks or 5 half-lives from any investigational (not FDA-approved) agents or FDA-approved non-nitrosourea chemotherapy (whichever is shorter) * Patients must have the following organ and marrow function: * Absolute neutrophil count \>1,000/mcL * Platelets \>100,000/mcL * Hemoglobin \> 9 g/dL * Total bilirubin \< 1.5 x institutional upper limit of normal (ULN) OR total bilirubin \>1.5 × ULN with direct bilirubin \< 1.5 × ULN; * AST (SGOT) and ALT (SGPT) \< 2.5 x institutional ULN * PT or PTT \< 1.5 x institutional ULN * Creatinine ≤ 1.5 x institutional ULN OR * Estimated glomerular filtration rate (eGFR) ≥50 mL/min/1.73 m2 calculated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation * Patient must be able to provide written informed consent. * All adverse events related to prior therapies (chemotherapy; radiotherapy; surgery) must have resolved to Grade 1 or baseline except for * Alopecia (Grade ≤2) * Sensory neuropathy (Grade ≤2) * Lymphopenia (Grade \<2) * Other adverse events that have resolved to Grade ≤2 that, according to the clinical judgment of the investigator, do not constitute a safety risk to the participant. * Ability to swallow and retain orally administered medications, including a liquid suspension. * Female participants of childbearing potential (defined as all females who have experienced menarche and who are not postmenopausal or surgically sterile) must have a negative serum pregnancy test prior to study start. Surgical sterility (methods inclusive of hysterectomy, bilateral salpingectomy, and bilateral oophorectomy) or post-menopausal state (amenorrhea for ≥24 months without an alternative medical cause and FSH ≥30 mIU/mL) must be confirmed. Female participants of childbearing potential must agree to use highly effective contraception or practice true abstinence (defined as refraining from heterosexual intercourse during the entire specified period) and not to donate ova from screening through 30 days after the last dose of plixorafenib or 120 days after last dose of retifanlimab. Highly effective contraception is defined as 1) intrauterine device, 2) abstinence, or 3) combined estrogen and progesterone or progesterone only containing implants, injectables, transdermal, or intravaginal contraceptives. * Male participants must also be documented to be surgically sterile or agree to use adequate contraception and not to donate sperm from screening until 30 days after the last dose of plixorafenib or 120 days after last dose of retifanlimab. * Patients must have no concurrent malignancy except curatively treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix, breast, or bladder. Patients with other malignancies must be disease-free for \> 2 years. * Life expectancy equal or greater than six months. Exclusion Criteria Exclusion Arm A Only: * Prior RAF dimer disruptor or pan-RAF inhibitor. Exclusion Arm B Only: * Prior immunotherapy (of note prior RAF dimer-disruptor or pan-RAF inhibitor is allowed). * Known history of clinically significant autoimmune disease that, in the opinion of the investigator, may be exacerbated by immune checkpoint blockade (e.g., multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease), with the following exceptions: Subjects with type I diabetes mellitus, hypothyroidism only requiring hormone replacement, skin disorders (such as vitiligo, psoriasis or alopecia) not requiring systemic treatment (subjects with a history of flares requiring systemic treatment are excluded), or other autoimmune conditions not expected to recur in the absence of an external trigger are permitted to enroll. * Daily systemic steroids \> 4mg daily dexamethasone or equivalent. * Have received a live vaccine within 28 days before the planned start of study treatment. Exclusion Both Arms: * Current use of any other standard or investigatio