[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Daniel Morgenstern\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":69},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,42],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":18,"enrollmentInfo":19,"targetDuration":4,"studyType":22,"phases":23,"briefSummary":25,"conditions":26,"keywords":4,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":30,"lastUpdatePostDateStruct":31,"startDateStruct":34,"completionDateStruct":36,"leadSponsor":38,"locationsCount":41},"100556022","a-pilot-study-investigating-upfront-adaptive-immunotherapy-approach-in-children-adolescent-and-young-adult-caya-patients-with-replication-repair-deficient-rrd-high-grade-gliomas-hgg-100556022",false,"NCT06519682","A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)","U-R-Immune Glioma (CA209-1245): A Pilot Study Investigating Upfront Adaptive Immunotherapy Approach in Children, Adolescent and Young Adult (CAYA) Patients With Replication-Repair Deficient (RRD) High-Grade Gliomas (HGG)","Inclusion Criteria:\n\n* 3.1.1 Age: Patients must be ≥12 months and ≤25 years of age at the time of signing informed consent\u002Fassent.\n\n3.1.2 Diagnosis: Patients must have a histologically confirmed diagnosis of glioblastoma.\n\n3.1.3 Proof of RRD: By tumor immunohistochemistry showing functional loss of mismatch repair gene expression (MLH1, MSH2, MSH6, PMS2), or based on prior germline testing confirming congenital mismatch repair deficiency (CMMRD) or Lynch syndrome. To be done locally. Results have to be available within four weeks of last surgery.\n\n3.1.4 Tumor Tissue Specimen: Provide a tumor tissue specimen for molecular profiling, including TMB analysis. Any tumor sequencing data if available at time of enrolment will be recorded for relevant pathogenic variants in the mismatch repair and polymerase-proofreading genes to suggest RRD. A specimen from the time of relapse\u002F progression while on the study is required as well, when applicable.\n\n3.1.5 Favorable immune markers: High PD1 and CD8 positivity as detailed in the lab manual. To be done locally. Results have to be available within 4 weeks of last surgery.\n\n3.1.6 Surgical and disease status: Patients should have had Gross total resection (GTR)\u002FNear Total Resection (NTR) as confirmed by the post-surgery scan. Patients are allowed a second look surgery to achieve NTR\u002FGTR provided no tumor directed systemic or radiation therapy has been administered before this second surgery. Patients should be able to start therapy within 4 weeks of last surgery.\n\n3.1.7 Allowable Prior Therapy: 3.1.7.1 Patients must have recovered from the acute toxic effects of all prior anti-cancer therapies (with the exception of alopecia and lymphopenia). Previous treatment with nivolumab and\u002For other anti- PD-1\u002FPD-L1 inhibitors for other prior tumors (other than high-grade glioma) will be permitted.\n\n3.1.7.2\n\nPrior Therapy: No prior therapy except surgery will be permitted for high grade glioma. If the patient was previously diagnosed and treated for another tumor (other than high grade glioma), the patients must have completed that treatment and have no active disease in order to be enrolled in this trial The following time periods apply for prior therapy for other tumors:\n\n* Cytotoxic chemotherapy: At least 21 days prior to initiation of protocol therapy from the last dose of cytotoxic or myelosuppressive chemotherapy; at least 42 days if prior nitrosourea (such as lomustine, CCNU).\n* Hematopoietic growth factors: At least 7 days prior to initiation of protocol therapy from the last dose of short-acting growth factor; at least 14 days for long-acting.\n* Anti-cancer agents not known to be myelosuppressive: At least 7 days prior to initiation of protocol therapy from the last dose.\n* Interleukins, interferons, and cytokines (other than hematopoietic growth factors): At least 21 days prior to initiation of protocol therapy from the last dose.\n* Antibodies: At least 21 days prior to initiation of protocol therapy from the last dose and toxicity related to prior antibody therapy must be recovered to Grade ≤1.\n* Radiotherapy: At least 14 days prior to initiation of protocol therapy from local radiotherapy; at least 150 days from total body irradiation (TBI), craniospinal radiotherapy, or radiation to\n\n  ≥50% of the pelvis; at least 42 days from other substantial bone marrow radiation.\n* Radiopharmaceutical therapy (e.g., 131I-MIBG): At least 42 days prior to initiation of protocol therapy from systemically administered radiopharmaceutical therapy.\n* Autologous stem cell infusion including boost infusion: At least 42 days prior to initiation of protocol therapy.\n* Cellular therapy: At least 42 days prior to initiation of protocol therapy from any type of cellular therapy.\n\n3.1.8 Performance Status: Lansky play score ≥50 if ≤16 years of age; Karnofsky performance scale ≥50 if \\>16 years of age. See Appendix A. Patients unable to walk due to paralysis but who are using a wheelchair will be considered ambulatory for the purpose of assessing the performance score.\n\n3.1.9 Organ Function: 3.1.9.1\n\nAdequate bone marrow function defined as:\n\n* peripheral absolute neutrophil count (ANC) ≥750\u002Fmm3 (0.75x109\u002FL)\n* platelet count ≥75,000\u002Fmm3 (75x109\u002FL), transfusion independent, defined as not receiving platelet transfusions at least 7 days prior to initiation of protocol therapy 3.1.9.2\n\nAdequate renal function defined as:\n\n-creatinine clearance or radioisotope GFR ≥60 mL\u002Fmin\u002F1.73 m2; OR serum creatinine based on age\u002Fgender 3.1.9.3\n\nAdequate liver function defined as:\n\n* bilirubin (sum of conjugated and unconjugated) ≤1.5 x upper limit of normal (ULN) for age\n* ALT (SGPT) ≤135 U\u002FL (i.e., 3 x ULN). For the purposes of this study, the ULN for ALT (SGPT) is 45 U\u002FL 3.1.9.4\n\nAdequate pulmonary function defined as:\n\n-no evidence of dyspnea at rest, no exercise intolerance due to pulmonary insufficiency, and pulse oximetry ≥92% while breathing room air 3.1.9.5\n\nAdequate cardiac function defined as:\n\n* no signs or symptoms of heart failure in a patient who has no history of congestive heart failure, no prior exposure to cardiotoxic drugs, and no radiotherapy to the heart; OR\n* shortening fraction of ≥27% or ejection fraction of ≥50% by echocardiogram 3.1.9.6\n\nAdequate pancreatic function defined as:\n\n-serum lipase ≤ ULN at screening 3.1.9.7\n\nViral Infection:\n\n* Human immunodeficiency virus (HIV): Infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to initiation of protocol therapy are eligible.\n* Hepatitis B virus (HBV): Patients with evidence of chronic infection with undetectable viral load are eligible. Suppressive therapy, if indicated, is allowed.\n* Hepatitis C virus (HCV): Infected patients currently on treatment with undetectable viral load are eligible. Patients with a history of infection must have been treated and cured.\n\nNote: Routine screening for HBV, HCV or HIV status prior to enrollment is not required.\n\n3.1.9.8 Informed Consent: All patients and\u002For their parents or legally authorized representatives must have the ability to understand and the willingness to sign, provide a thumbprint (e.g.., for illiterate patients), or use an authorized method to duly document the informed consent in line with the local IRB\u002FIEC requirements and the regulations in force). Assent, where appropriate, will be obtained according to local regulations.\n\nExclusion Criteria:\n\n* 3.2.1\n\nConcomitant Medications:\n\n* Corticosteroids: Patients requiring systemic corticosteroids or other forms of immunosuppressive therapy within 7 days prior to initiation of protocol therapy are not eligible.\n* Following initiation of protocol therapy, systemic corticosteroids or other forms of immunosuppressive therapy are permitted if administered for the treatment of toxicity, tumor flare, or pseudo-progression and can be tapered. In most cases protocol therapy must be held until the dose is tapered to 10 mg\u002Fday prednisone or equivalent. The Protocol Principal Investigator must be consulted prior to resuming treatment.\n* Physiologic corticosteroids up to 5 mg\u002Fday prednisone or equivalent are permitted.\n* Topical, ocular, intra-articular, intra-nasal, and inhaled corticosteroids are permitted.\n* Patients with CNS tumors receiving steroids must be able to discontinue these at least 7 days prior to initiation of protocol therapy.\n* Anti-cancer agents: Patients who are currently receiving other anti-cancer agents are not eligible.\n* Other investigational agents: Patients who are currently receiving or have received any other investigational agent within 14 days prior to initiation of protocol therapy are not eligible.\n\n3.2.2\n\nCNS Tumor Bulk: Patients with CNS tumors with any of the following characteristics on imaging are not eligible:\n\n* Tumor with any evidence of uncal herniation or mass effect leading to severe midline shift\n* Tumor that in the opinion of the local investigator, shows significant mass effect after initial surgery or after second-look surgery.\n\n3.2.3 Uncontrolled Intercurrent Illness: Patients with uncontrolled intercurrent illness including, but not limited to, ongoing active infection, symptomatic congestive heart failure (New York Heart Association Class III or IV), unstable angina pectoris, cardiac arrhythmia, or psychiatric illness\u002Fsocial situations that would limit compliance with study requirements are not eligible.\n\n3.2.4 Pregnant and\u002For Breastfeeding: The study agents have the potential for teratogenic or abortifacient effects. Females of reproductive potential must have a negative serum pregnancy test within 72 hours prior to initiation of protocol therapy. Additional pregnancy tests (serum or urine) should be obtained during study participation in accordance with local standards and guidelines.\n\nMales or females of reproductive potential may not participate unless they have agreed to use an effective method of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry, for the duration of treatment, and as follows:\n\n●Females receiving nivolumab must continue an effective method of contraception for a period of 5 months after the last dose of nivolumab.\n\nShould a female patient become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform the investigator immediately.\n\nDue to the unknown but potential risk for AEs in nursing infants secondary to treatment of the mother with the study agents, breastfeeding must be discontinued if the mother is treated on study.\n\nNote: Females of reproductive potential are defined as those who are past the onset of menarche and are not surgically sterile (i.e., bilateral salpingectomy, bilateral oophorectomy, or complete hysterectomy).\n\n3.2.5 Autoimmune Disease: Patients with a history of autoimmune disease (such as autoimmune thyroid disease or inflammatory bowel disease) that has required systemic treatment within 2 years prior to initiation of protocol therapy are not eligible.\n\n* Asymptomatic laboratory abnormalities (e.g., ANA, rheumatoid factor, altered thyroid studies) will not render a patient ineligible in the absence of a diagnosis of an autoimmune disorder.\n* Patients with atopy-related conditions such as asthma, allergic rhinitis, or atopic dermatitis are not excluded.\n* Replacement therapy (e.g., thyroxine, insulin, or physiological corticosteroid replacement therapy) is not considered a form of systemic treatment.\n\n3.2.6 Interstitial Lung Disease: Patients with history of interstitial lung disease or pneumonitis are not eligible.\n\n3.2.7 Transplant: Patients who have received previous solid organ transplant or allogenic stem cell transplant are not eligible.\n\n3.2.8 Adverse Reaction to Study Agent(s): Patients with previous Grade 4 life-threatening reaction or other adverse reaction that in the opinion of the investigator would preclude retreatment with nivolumab, and\u002For other PD-1\u002FPD-L1 antibodies are not eligible.\n\n3.2.9 Compliance: Patients who in the opinion of the investigator may not be able to comply with the safety monitoring requirements of the study are not eligible.\n\n3.2.10 Treatment Start: Patients unable to start study protocol treatment within 14 days from the enrollment date or within 4 weeks of surgery (whichever is earlier).\n\n3.3 Specific Criteria for Domain 2 3.3.1 Proceeding from Domain 1 to Domain 2 For patients already enrolled on the study, the following exclusion criteria specifically apply prior to proceeding to Domain 2.\n\n3.3.1.1 Specific Exclusion Criteria\n\n* Surgery: Patient who cannot have surgery\u002Fbiopsy at recurrence\u002Fprogression on Domain 1 will be discontinued from the study.\n* CNS Tumor Bulk: Patients with CNS tumors with any of the following characteristics on imaging post-surgery\u002Fbiopsy at progression\u002Frecurrence on Domain 1 are not eligible:\n\n  * Tumor \\>= 5cm in the longest dimesion.\n  * Tumor with any evidence of uncal herniation or mass effect leading to severe midline shift\n  * Tumor that in the opinion of the local investigator, shows significant mass effect","ALL","12 Months","25 Years",{"count":20,"type":21},20,"ESTIMATED","INTERVENTIONAL",[24],"NA","This is open label, multicentre, single arm, pilot study of upfront nivolumab in patients with RRD-glioblastoma with favorable immune\u002Fgenomic biomarkers. The purpose of the study is to use upfront immune checkpoint inhibitor (ICI) to delay\u002Favoid radiation for patients with RRD-glioblastoma with favorable clinical (Gross total resection (GTR) or near total resection (NTR)) and biological (RRD, hypermutation, immune activation) biomarkers. At progression, patients will be undergoing surgery\u002Fbiopsy and will get a combination of radiation + ICI followed by maintenance ICI. This model will allow us to additionally study the evolution tumor in response to ICI. The study will have two domains.",[27,28],"High Grade Glioma","Replication Repair Deficient","RECRUITING","2025-08-22",{"date":32,"type":33},"2025-08-29","ACTUAL",{"date":35,"type":33},"2024-12-06",{"date":37,"type":21},"2029-08",{"name":39,"class":40},"Daniel Morgenstern","OTHER",1,{"id":43,"slug":44,"hasResults":11,"nctId":45,"briefTitle":46,"officialTitle":47,"acronym":48,"eligibilityCriteria":49,"healthyVolunteers":11,"sex":16,"minAge":50,"maxAge":18,"enrollmentInfo":51,"targetDuration":4,"studyType":22,"phases":53,"briefSummary":55,"conditions":56,"keywords":58,"overallStatus":29,"whyStopped":4,"lastUpdateSubmitDate":61,"lastUpdatePostDateStruct":62,"startDateStruct":64,"completionDateStruct":66,"leadSponsor":68,"locationsCount":41},"100545412","early-phase-1-pilot-study-of-vinblastine-and-tovorafenib-in-pediatric-patients-with-recurrentprogressive-raf-altered-low-grade-gliomas-100545412","NCT06381570","Pilot Study of Vinblastine and Tovorafenib in Pediatric Patients With Recurrent\u002FProgressive RAF Altered Low Grade Gliomas","VICTORY: A Pilot Study to Investigate Safety and Efficacy of Weekly Combination of Intravenous Vinblastine With Oral Type II RAF Inhibitor Tovorafenib in Pediatric Patients With Recurrent\u002FProgressive RAF Altered Low Grade Gliomas","VICTORY","Inclusion Criteria:\n\n1. Age\n\n   a) Patients must be less than or equal to 25 years of age at the time of enrollment.\n2. Study Group\n\n   a) Progressive\u002FRecurrent LGG (non-NF1) with documented BRAF or CRAF alteration as identified through molecular assays as routinely performed at CLIA or other similar certified laboratories.\n3. Diagnosis\n\n   1. All patients must have pathological confirmation of low-grade glioma with BRAF or CRAF alteration.\n   2. Patient must have progressive or recurrent LGG.\n   3. Must have at least 1 measurable lesion, as defined by RANO-LGG criteria.\n   4. Eligible histologies will include all tumors considered low-grade glioma or low-grade astrocytoma (WHO grade I and II) by WHO classification of Tumors of the Central Nervous system -5th edition revised with exception of subependymal giant cell astrocytoma.\n4. Prior Therapy\n\n   1. Must have received at least 1 line of systemic therapy prior (at least a vinca alkaloid and\u002For single agent carboplatin and\u002For a MEK or BRAF inhibitor) and have documented evidence of radiographic progression.\n   2. Patients must have fully recovered from the acute toxic effects (≤ Grade I) of all prior anticancer chemotherapy and have undergone the following washout periods, as applicable.\n\n   i. Myelosuppressive chemotherapy: At least 21 days after the last dose of myelosuppressive chemotherapy (42 days if prior nitrosourea) ii. Radiation therapy (XRT): Radiation therapy to the measurable lesion(s) must be completed at least 6 months prior to administration of combination therapy. Patients who have documented radiographic progression less than 6 months from radiotherapy in 1 or more measurable lesions are eligible. At least 2 weeks after the last dose fraction of XRT to the non-target lesion.\n\n   iii. Investigational agent or any other anticancer therapy not defined above: At least four weeks prior to planned start of combination therapy, or five half-lives, whichever is shorter.\n\n   iv. Patients must have recovered from acute effects of any prior surgery. v. Chronic toxicities from prior anticancer therapy must be stable as per Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 Grade ≤ 2, except ongoing retinopathy which must be ≤ Grade 1.\n5. Performance Level\n\n   a) Karnofsky (those 16 years and older) or Lansky (those younger than 16 years) performance score of at least 50. Patients who are unable to walk because of paralysis, but who are able to sit in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score.\n6. Tumor Tissue Sample Confirmation that an archival tumor tissue sample is available. If an archival tumor tissue sample is not available, a fresh biopsy should be performed at baseline. Submission of tumor tissue and a blood sample are mandatory and must be submitted within 14 days from enrollment onto the study and prior to initiation of treatment. Biopsy may be either at initial diagnosis or recurrence.\n7. Organ function\n\n   a) Adequate bone marrow function defined as: i. Absolute neutrophil count ≥ 1000\u002Fmm3 ii. Platelet count (unsupported) ≥ 100 x 109\u002FL (transfusions allowed per institutional guidelines; last transfusion \\> 2 weeks prior to enrollment) iii. Hemoglobin (unsupported)≥ 10.0 g\u002FdL (transfusions allowed per institutional guidelines; last transfusion \\> 4 weeks prior to enrollment) iv. Hematopoietic growth factors: At least 14 days after the last dose of a long-acting growth factor (e.g., Neulasta®) or 7 days for short-acting growth factor.\n\n   b) Adequate hepatic and renal function defined as: i. Total bilirubin ≤ 1.5 x upper limit of normal (ULN) for age (patients with documented Gilbert's disease may be enrolled with sponsor approval and total bilirubin ≤ 2 x ULN) ii. Serum glutamic-pyruvic transaminase (SGPT)\u002Falanine aminotransferase (ALT) ≤ 2.5 x ULN iii. Serum glutamic-oxaloacetic transaminase (SGOT)\u002Faspartate transaminase (AST) ≤ 2.5 x ULN iv. Serum creatinine within normal limits or estimated glomerular filtration rate\n\n   ≥ 60 ml\u002Fmin\u002F1.73 m2 based on local institutional practice for determination. c) Thyroid functions tests within institutional normal range. Patients on a stable dose of thyroid replacement therapy for a minimum of 3 weeks before starting therapy are eligible.\n\n   d) Adequate cardiac function defined as: i. Left ventricular ejection fraction (LVEF) of ≥ 50% as measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scan, or fractional shortening (FS) ≥ 25% (Tissot et al., 2018) as measured by ECHO, within 14 days before enrollment (while not receiving medications for cardiac function). If normal practice at the institution is to provide the LVEF result as a range of values, then the upper value of the range will be used to determine the result.\n\n   ii. QTc (by Fridericia's formula) \\\u003C 470ms as measured by electrocardiogram (ECG) within 14 days before enrollment (while not receiving medications for cardiac function).\n\n   e) Adequate central nervous system (CNS) function defined as: i. Patients with seizures should be stable and not have experienced a significant increase in seizure frequency within 14 days prior to enrollment.\n\n   ii. Patients with neurologic deficits should have deficits that are stable for a minimum of 14 days prior to enrollment.\n\n   iii. Patients receiving steroids for tumor-associated symptoms must be on a stable dose (e.g., no initial\u002Floading dose, no increase or decrease) for 14 days prior to enrollment.\n8. Study specific\n\n   1. Baseline ophthalmology assessment within 28 days of study enrollment.\n   2. MRI assessment within 28 days of study enrollment. MRI done for clinical indication but within the window for study would be permitted as baseline.\n   3. Ability to comply with treatment, laboratory monitoring, and required clinic visits for the duration of study participation.\n   4. Willingness of male and female patients with reproductive potential to use double effective birth control methods, defined as one used by the patient and another by his\u002Fher partner, for the duration of treatment and for 180 days following the last dose of study drug. Effective birth control methods are described in Appendix H.\n   5. Ability to swallow tablets or liquid, or gastric access via a nasal or gastric tube.\n   6. Patient is able to start treatment within 14 working days of screening.\n   7. Parent\u002Fguardian of child or adolescent patient has the ability to understand, agree to, and sign the study ICF and applicable pediatric assent form before initiation of any protocol related procedures; patient has the ability to give assent, as applicable, at the time of parental\u002Fguardian consent.\n\nExclusion Criteria:\n\n* Patients meeting any of the following criteria are to be excluded from study participation:\n\n  1. Patient's tumor has additional previously known activating molecular alterations, other than BRAF or CRAF.\n  2. Known or suspected diagnosis of neurofibromatosis Type 1 (NF-1) via genetic testing or current diagnostic clinical criteria.\n  3. History of any major disease, other than the diagnosis of LGG, that might interfere with safe protocol participation.\n  4. Patient with a history or current evidence of central serous retinopathy (CSR), retinal vein occlusion (RVO), or ophthalmopathy present at baseline who would be considered a risk factor for CSR or RVO. Ophthalmological findings secondary to long-standing optic pathway glioma (such as visual loss, optic nerve pallor, or strabismus) will NOT be considered a significant abnormality for the purposes of this study.\n  5. Major surgery within 14 days (2 weeks) prior to enrollment (does not include central venous access, cyst fenestration or cyst drainage, or ventriculoperitoneal shunt placement or revision).\n  6. Clinically significant active cardiovascular disease, or history of myocardial infarction, or deep vein thrombosis\u002Fpulmonary embolism within 6 months prior to enrollment, ongoing cardiomyopathy, or current prolonged QT interval corrected for heart rate by Fridericia's formula (QTcF) interval \\> 470 ms based on triplicate ECG average.\n  7. Concomitant medications that are strong inhibitors or inducers of CYP2C8 or CYP3A4 within 14 days before initiation of therapy. Concomitant medications that are substrates of BCRP with a narrow therapeutic index within 14 days before initiation of therapy\n  8. Current enrollment in any other investigational treatment study. Participation on a concurrent observational or bio-sampling study is allowed.\n  9. Active systemic bacterial, viral, or fungal infection.\n  10. Nausea and vomiting ≥ National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) 5.0 Grade 2 (for those not controlled by supportive care), malabsorption requiring supplementation, or significant bowel or stomach resection that would preclude adequate absorption of tovorafenib.\n  11. Patient has CTCAE v5.0 Grade 3, creatine phosphokinase (CPK) elevation (\\> 5 × ULN - 10 × ULN).\n  12. Patients who are neurologically unstable despite adequate treatment (e.g., uncontrolled seizures).\n  13. Pregnancy or lactation.\n  14. History of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome or Stevens Johnsons syndrome (SJS). Patients with hypersensitivity to the investigational medicinal product or to any drug with similar chemical structure or to any other excipient present in the pharmaceutical form of the investigational medicinal product.\n  15. Other unspecified reasons that, in the opinion of the investigator, make the patient unsuitable for enrollment.","0 Weeks",{"count":52,"type":21},57,[54],"EARLY_PHASE1","This is a Pilot, multicenter, open-label study of patients less than or equal to 25 years, with recurrent or progressive LGG harboring a CRAF or BRAF alteration, including BRAF V600 mutations and KIAA1549: BRAF fusions. Patients with BRAF or CRAF alterations will be identified through molecular assays as routinely performed at Clinical Laboratory Improvement Amendments (CLIA) of 1988 or other similarly certified laboratories.\n\nThe study will be conducted in two sequential phases:\n\nPhase A: A Feasibility (combination dose finding) phase, followed by Phase B: An Efficacy phase. The maximum tolerated dose (MTD)\u002FRecommended Phase 2 Dose (RP2D) of the combination as determined in Phase A would be the dose used in Phase B. The patients on Phase A who were below the MTD\u002FRP2D would be eligible for intra-patient dose escalation to MTD\u002FRP2D subject to criteria outlined later",[57],"Low-grade Glioma",[59,60],"RAF altered","non-NF1","2025-05-12",{"date":63,"type":33},"2025-05-15",{"date":65,"type":33},"2024-03-21",{"date":67,"type":21},"2029-03-21",{"name":39,"class":40},""]