[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"leadSponsorName\":\"Nader Sanai\",\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:":119},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,4,0,[8,44,74,96],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":4,"eligibilityCriteria":15,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":18,"targetDuration":4,"studyType":21,"phases":22,"briefSummary":24,"conditions":25,"keywords":27,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":32,"lastUpdatePostDateStruct":33,"startDateStruct":36,"completionDateStruct":38,"leadSponsor":40,"locationsCount":43},"100584008","early-phase-1-clinical-trial-of-bms-986504-in-recurrent-gbm-patients-100584008",false,"NCT06883747","Clinical Trial of BMS-986504 in Recurrent GBM Patients","A Phase 0\u002F1 Study of BMS-986504, a MTA Cooperative PRMT5 Inhibitor in Recurrent Glioblastoma Participants With MTAP Deleted Tumors Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With PK-Triggered Expansion Cohort","Inclusion Criteria:\n\n* Participants with the diagnosis of glioblastoma by the 2021 WHO criteria, who have progressed on or following previous tumor-directed therapy, which must have included a maximal safe resection (biopsy allowed if it was deemed unsafe to resect) and fractionated radiotherapy (RT).\n* Patients with archival tissue demonstrating MTAP loss\u002Fdeletion confirmed through NGS will be qualified for Phase 0 portion of the study.\n* Participants must have measurable disease preoperatively, defined as at least 1 contrast-enhancing lesion, with 2 perpendicular measurements of at least 1 cm.\n* Participants who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \\[CTCAE\\] Grade ≤ 1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to Day 1. A washout period of at least 21 days is required between the last chemotherapy dose and Day 1 (provided the participant did not receive RT).\n* Age ≥ 18 at time of consent\n* Have a performance status (PS) of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) scale\n* Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):\n\n  * Adequate Bone Marrow Function: Absolute neutrophil count ≥ 1,500\u002FmcL; Platelets (at time of surgery) ≥ 100,000\u002FmcL; Hemoglobin ≥ 9.0 g\u002FdL (participants may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.)\n  * Adequate Hepatic Function: Total Bilirubin ≤ 1.5 X ULN; Participants with Gilbert's syndrome with a total bilirubin ≤ 2.0 times ULN and direct bilirubin within normal limits are permitted; AST (SGOT) ≤ 3 X institutional ULN; ALT (SGPT) ≤ 3 X institutional ULN\n  * Adequate Renal Function: Estimated glomerular filtration rate (eGFR) ≥ 60 mL\u002Fmin\u002F1.73 m2 by Chronic Disease Epidemiology Collaboration (CKD-EPI) equation; Serum creatinine ≤ 1.5 X ULN or estimated creatinine clearance \\>\u002F= 60 mL\u002Fmin (calculated using Institutional standard method)\n  * Coagulation Function: INR ≤ 1.5 X ULN\n* Ability to swallow oral medications without crushing or chewing.\n* Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.\n* For females of reproductive potential: use of highly effective contraception for at least 28 days prior to treatment and agreement to use such a method during study participation and for an additional 7 months after the end of treatment administration.\n* Females of child-bearing potential must agree not to breastfeed starting at screening, throughout the study period and for 7 months after final study drug administration.\n* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and avoid sperm donation for the duration of the study and for an additional 4 months after the end of treatment administration.\n* Agreement to adhere to Lifestyle Considerations throughout study duration.\n* Willingness and ability to comply with scheduled visits, treatment plans, laboratory tests and other procedures.\n* Participant understands the informed consent document and has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.\n\nExclusion Criteria:\n\n* Inability to undergo MRI brain with intravenous (IV) contrast\n* Known active systemic bacterial infection (IV antibiotics or fever \\> 38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \\[for example, hepatitis B surface antigen positive\\]. Screening of viral infection is not required for enrollment.\n* Cardiovascular abnormalities including:\n\n  * LVEF \\\u003C 50%\n  * History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation \\> 480 msec, except for right bundle branch block.\n  * Uncontrolled\u002Fsymptomatic or significant cardiovascular conditions within 6 months prior to enrollment, including but not limited to any of the following: Cardiac angioplasty or stenting, unstable angina pectoris, myocardial infarction, stroke\u002Ftransient ischemic attack, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, New York Heart Association (NYHA) class III-IV congestive heart failure, pericarditis, atrial fibrillation or other arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).\n* Symptomatic or radiographic leptomeningeal disease.\n* Known other concurrent severe and\u002For uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risks, contraindicate patient participation in the clinical study or compromise compliance with the protocol (e.g., Celiac disease, Crohn's disease, gastric bypass, malabsorption, chronic pancreatitis, chronic active hepatitis, active untreated or uncontrolled fungal, bacterial or viral infections, etc.).\n* With the exception of alopecia, any unresolved toxicities from prior therapy greater than National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE v5.0) Grade 1 at the time of starting study treatment and patients with chronic Grade 2 unresolved toxicities may be eligible following discussion with the Principal Investigator.\n* Treatment with another investigational drug or other intervention within 5 half-lives of the investigational product whichever is longer.\n* Prior treatment with another PRMT5 inhibitor.\n* Known allergic reactions to components of BMS-986504: microcrystalline cellulose, croscarmellose sodium, colloidal silicon dioxide, magnesium stearate, polyvinyl alcohol, titanium dioxide, polyethylene glycol\u002Fmacrogol, and talc.\n* Use of strong inhibitors and strong inducers of CYP3A4\u002FP-gp. Consider using alternative medications, per Investigator judgment.\n* Concurrent use of medications known to prolong the QT interval (e.g., certain antiarrhythmics, antibiotics, antipsychotics, and antidepressants) unless discontinued for an appropriate washout period as determined by the investigator.\n* Participants who have received live\u002Fattenuated vaccine within 30 days of anticipated first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted on study without restriction.","ALL","18 Years",{"count":19,"type":20},12,"ESTIMATED","INTERVENTIONAL",[23],"EARLY_PHASE1","This is an open-label, multi-center, Phase 0\u002F1 dose-escalation trial designed to enroll up to 12 total recurrent glioblastoma (rGBM) participants with confirmed MTAP loss\u002Fdeletion in their archival or pretreatment biopsy tissue, who are scheduled for surgical resection. MTAP loss\u002Fdeletion will be determined by next-generation sequencing (NGS). The trial will include a dose escalation design to evaluate the pharmacokinetics (PK) and safety and tolerability of BMS-986504 (MRTX1719). The trial will be composed of a Phase 0 component and an Expansion Phase 1 component. Participants with tumors demonstrating a positive PK response in the Phase 0 component of the study will be eligible to enroll into the the Phase 1 component that will include 21-day cycles of therapeutic dosing of BMS-986504.",[26],"Glioblastoma WHO Grade IV",[28,29,30],"MTAP loss","MTAP deletion","MTAP del","RECRUITING","2026-06-22",{"date":34,"type":35},"2026-06-25","ACTUAL",{"date":37,"type":35},"2025-04-28",{"date":39,"type":20},"2027-09-28",{"name":41,"class":42},"Nader Sanai","OTHER",1,{"id":45,"slug":46,"hasResults":11,"nctId":47,"briefTitle":48,"officialTitle":49,"acronym":4,"eligibilityCriteria":50,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":51,"targetDuration":4,"studyType":21,"phases":53,"briefSummary":54,"conditions":55,"keywords":57,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":66,"lastUpdatePostDateStruct":67,"startDateStruct":69,"completionDateStruct":71,"leadSponsor":73,"locationsCount":43},"100630236","early-phase-1-bgb-58067-in-newly-diagnosed-glioblastoma-patients-with-mtap-deleted-tumors-100630236","NCT07485049","BGB-58067 in Newly Diagnosed Glioblastoma Patients With MTAP-Deleted Tumors","A Phase 0\u002F2 Study of BGB-58067, an MTA Cooperative PRMT5 Inhibitor, in Newly Diagnosed Glioblastoma Patients With Methylthioadenosine Phosphorylase (MTAP) Deleted Tumors Scheduled for Resection to Evaluate Central Nervous System (CNS) Penetration With Pharmacodynamic (PD)-Triggered Expansion Cohorts","Inclusion Criteria:\n\n* 1\\. Suspected newly diagnosed glioblastoma according to 2021 WHO criteria who have not received any tumor directed intervention other than biopsy.\n* 2\\. Has measurable disease (preoperatively), defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.\n* 3\\. Age ≥ 18 at time of consent.\n* 4\\. Has a performance status of ≤ 2 on the ECOG scale.\n* 5\\. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):\n\n  1. Adequate Bone Marrow Function Absolute neutrophil count ≥ 1500\u002FμL (≥ 1.5 x 109\u002FL) Platelets (at time of surgery) ≥ 100,000\u002FμL (≥ 100 x 109\u002FL) Hemoglobin ≥ 9.0 g\u002FdL or ≥ 5.6 mmol\u002FL (Criteria must be met without erythropoietin dependency and without pRBC transfusion within prior 2 weeks.)\n  2. Adequate Hepatic Function Total Bilirubin ≤ 1.5x ULN (Participants with Gilbert's syndrome with a total bilirubin ≤ 3x ULN and direct bilirubin ≤ 1.5x ULN will be permitted.) AST (SGOT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \\\u003C 5x ULN will be permitted) ALT (SGPT) ≤ 2.5x institutional ULN (Participants with liver metastases with ALT \\\u003C 5x ULN will be permitted.)\n  3. Adequate Renal Function eGFR ≥ 60 mL\u002Fmin\u002F1.73 m2 (Calculated as individualized eGFR using the CKD-EPI formula \\[2021\\]) If measured or calculated GFR (e.g., creatinine clearance; mGFR) is required or used: ≥ 60 mL\u002Fmin\n  4. Adequate Metabolic Function Albumin ≥ 2.8 g\u002FdL\n  5. Adequate Coagulation INR or PT and aPTT ≤ 1.5x ULN\n* 6\\. For females of childbearing potential:\n\n  1. Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first dose of study treatment); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy.\n  2. Must use a highly effective method of contraception (with a failure rate of \\\u003C1% per year and low user dependency) for at least 28 days prior to treatment, and agree to use such a method during study participation and for an additional 6 months after final study drug administration.\n  3. Agrees not to breastfeed starting at screening, during study participation, and for 6 months after final study drug administration.\n  4. Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for 6 months after final study drug administration.\n* 7\\. For females of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.\n* 8\\. For males:\n\n  1. Agrees not to donate sperm starting at screening, during study participation, and for 3 months after final study drug administration.\n  2. Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agrees to remain abstinent starting at screening, during study participation, and for 3 months after final study drug administration.\n\nOR Must use a male condom and their female partner must use an additional highly effective method of contraception (with a failure rate of \\\u003C1% per year and low user dependency) starting at screening, during study participation, and for 3 months after final study drug administration.\n\n* 9\\. Agrees to adhere to protocol defined Lifestyle Considerations throughout study duration.\n* 10\\. Able and willing to comply with scheduled visits, treatment plans, laboratory tests and other procedures.\n* 11\\. Understands the informed consent document and has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.\n\nExclusion Criteria:\n\n* 1\\. Unable to undergo MRI of the brain with intravenous (IV) contrast.\n* 2\\. Has a known active systemic bacterial infection (on IV antibiotics or has fever \\> 38.5°C at time of initiating study treatment) or fungal infection, or has a detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \\[e.g., hepatitis B surface antigen positive\\]). NOTE: Screening of viral infection is not required for enrollment.\n* 3\\. Has cardiovascular abnormalities including:\n\n  1. LVEF \\\u003C 50%\n  2. History of prolonged QTc, or QT interval corrected for heart rate using Fridericia's formula (QTcF) prolongation \\> 480 msec, except for right bundle branch block.\n  3. Uncontrolled\u002Fsymptomatic or significant cardiovascular conditions within 6 months prior to enrollment, including but not limited to any of the following: cardiac angioplasty or stenting, unstable angina pectoris, myocardial infarction, stroke\u002Ftransient ischemic attack, coronary artery bypass graft surgery, symptomatic peripheral vascular disease, New York Heart Association (NYHA) class III or IV congestive heart failure, pericarditis, atrial fibrillation or other arrhythmias (e.g., ventricular tachycardia, ventricular fibrillation, or Torsades de Pointes).\n* 4\\. Has symptomatic or radiographic leptomeningeal disease.\n* 5\\. Has other known concurrent severe psychiatric and\u002For uncontrolled medical condition that, in the investigator's judgment, would cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol.\n* 6\\. Has received prior treatment with another investigational drug or other intervention within 5 half lives of the investigational product, whichever is longer.\n* 7\\. Has received prior treatment with another PRMT5 inhibitor.\n* 8\\. Has known allergic reactions to components of BGB-58067.\n* 9\\. Patients who require ongoing treatment with a strong CYP3A or CYP2C8 inhibitor or inducer, ≤ 5 half-lives or ≤ 14 days, whichever is shorter or known. Consider using alternative medications, per Investigator judgment.\n* 10\\. Has received a live\u002Fattenuated vaccine within 30 days of anticipated first treatment. The use of inactivated seasonal influenza vaccines (e.g., Fluzone®) will be permitted.\n* 11\\. Is pregnant or breastfeeding.",{"count":52,"type":20},78,[23],"This is an open-label, multi-center, Phase 0\u002F2 trial designed to enroll up to 78 total participants with suspected newly diagnosed glioblastoma (nGBM) who are scheduled for surgical resection to accrue at least 14 participants in Arm A and 10 participants in Arm B. The trial will evaluate the pharmacokinetics (PK), pharmacodynamics (PD), and safety of BGB-58067.\n\nThe study is composed of a Phase 0 and expansion Phase 2 component. The Phase 0 primary endpoint will be suppression of symmetric dimethylarginine (SDMA) in tumor tissue measured by immunohistochemistry (IHC). The Phase 2 primary endpoint will be 12-month overall survival rate (OS12).\n\nThe Phase 0 secondary endpoint will be to characterize the PK of BGB-58067 in tumor tissue, plasma, and cerebrospinal fluid (CSF). The Phase 2 secondary endpoints will include assessing the safety profile of BGB-58067 and evaluating clinical efficacy of BGB 58067 using overall survival (OS) and the 6-month progression-free survival rate (PFS6) estimated by Kaplan-Meier (K-M) methods.",[56],"Glioblastoma (GBM)",[58,59,60,61,62,63,64,65],"MTAP-Deleted","MGMT Methylation","Methylthioadenosine Phosphorylase","O6-Methylguanine-DNA Methyltransferase","PRMT5 Inhibitor","PRMT5i","Newly Diagnosed Glioblastoma","Newly Diagnosed Grade 4 Glioma","2026-05-11",{"date":68,"type":35},"2026-05-14",{"date":70,"type":35},"2026-05-07",{"date":72,"type":20},"2028-11",{"name":41,"class":42},{"id":75,"slug":76,"hasResults":11,"nctId":77,"briefTitle":78,"officialTitle":79,"acronym":4,"eligibilityCriteria":80,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":81,"targetDuration":4,"studyType":21,"phases":83,"briefSummary":85,"conditions":86,"keywords":4,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":88,"lastUpdatePostDateStruct":89,"startDateStruct":91,"completionDateStruct":93,"leadSponsor":95,"locationsCount":43},"100511519","phase-2-abemaciclib-in-newly-diagnosed-meningioma-patients-100511519","NCT05940493","Abemaciclib in Newly Diagnosed Meningioma Patients","A Phase 2 Multicenter, Double-blind, Randomized-controlled Study of Abemaciclib (CDK4 and 6 Inhibitor) in Newly Diagnosed RB-proficient Grade 3 Meningioma Participants","Inclusion Criteria:\n\n* Participants with newly diagnosed intracranial WHO Grade 3 meningioma; or,\n* Participants with previous lower grade meningioma and histopathologically confirmed newly transformation to Grade 3.\n* Plan to receive or have received upfront standard of care radiation therapy (RT) for the newly diagnosed WHO Grade 3 meningioma.\n* No prior treatment for Grade 3 meningioma other than surgical resection or biopsy and upfront RT. If previously diagnosed with a lower grade meningioma, no prior treatment other than surgical resection or biopsy and no prior RT.\n* Ability to understand and the willingness to sign a written informed consent document (personally or by the legally authorized representative, if applicable).\n* Participant has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative\\[s\\], and assent, if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally document and witnessed, ideally via an independent trusted witness. Participant must be willing and able to comply with scheduled visits, treatment plans, laboratory tests and other procedures.\n* Age ≥18 years at time of consent.\n* Have a performance status (PS) of ≤2 on the Eastern Cooperative Oncology Group (ECOG) scale.\n* Ability to swallow oral medications.\n* Participant has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):\n\n  * Adequate Bone Marrow Function: absolute neutrophil count ≥1,500\u002FmcL, platelets ≥100,000\u002FmcL, and hemoglobin ≥8.0 g\u002FdL (individual may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator; initial treatment must no begin earlier than the day after any erythrocyte transfusion).\n  * Adequate Hepatic Function: total bilirubin ≤1.5x ULN (individuals with Gilbert's syndrome with a total bilirubin ≤2.0x ULN and direct bilirubin within normal limits are permitted), AST\u002FSGOT ≤3x ULN, and ALT\u002FSGPT ≤3x ULN.\n* Confirmed negative serum pregnancy test (β-hCG) before starting study treatment or participant who is no longer of childbearing potential due to surgical, chemical, or natural menopause.\n* For females of reproductive potential: use of highly effective contraception during study participation and for an additional 3 weeks after the end of treatment administration.\n* For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner and for an additional 3 weeks after the end of treatment administration.\n\nExclusion Criteria:\n\n* Prior history of cancer with ongoing treatment of disease.\n* Pregnancy or breastfeeding.\n* Known allergic reactions to components of the abemaciclib.\n* Active infection or fever \\>38.5°C requiring systemic antibiotic, antifungal or antiviral therapy within 4 weeks of Day 1.\n* Known to have active (acute or chronic) or uncontrolled severe infection, liver disease such as cirrhosis, decompensated liver disease, and active and chronic hepatitis.\n* Known active systemic bacterial infection (requiring IV antibiotics at time of initiating study treatment), fungal infection, or detectable viral infection (such as known HIV positivity or with known HBV or HCV). Screening is not required for enrollment.\n* Participant has serious and\u002For uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study.\n* Prior therapy with any CDK4\u002F6 inhibitor. Prior therapy is defined as therapeutic dosing.\n* Treatment with another investigational drug within 5 half-lives of the investigational product.",{"count":82,"type":20},72,[84],"PHASE2","This study is being done to learn about how an investigational drug called abemaciclib works in treating patients with a newly-diagnosed grade 3 meningioma. Abemaciclib is a drug that is approved by the FDA, but not for brain tumors.\n\nParticipants who consent to the trial will have surgical tissue collected from the planned surgical resection and tested. If the tissue shows positive results for RB cells and participants are qualified, they will be enrolled and receive study treatment two to five weeks after completing standard-of-care radiation therapy.\n\nThis is a randomized clinical trial which means that participants will be randomly assigned to a treatment based on chance, like a flip of a coin. Neither the participant nor the researcher chooses the assigned group. Randomization will help the researchers study how the drug works by comparing the difference between the study drug and the placebo and how they work in treating brain tumors. This is a double-blinded study, which means that neither the participant nor the study team will know which treatment the participant is receiving.",[87],"Meningioma","2026-03-11",{"date":90,"type":35},"2026-03-13",{"date":92,"type":35},"2025-03-24",{"date":94,"type":20},"2030-09",{"name":41,"class":42},{"id":97,"slug":98,"hasResults":11,"nctId":99,"briefTitle":100,"officialTitle":100,"acronym":4,"eligibilityCriteria":101,"healthyVolunteers":11,"sex":16,"minAge":17,"maxAge":4,"enrollmentInfo":102,"targetDuration":4,"studyType":21,"phases":104,"briefSummary":105,"conditions":106,"keywords":108,"overallStatus":31,"whyStopped":4,"lastUpdateSubmitDate":111,"lastUpdatePostDateStruct":112,"startDateStruct":114,"completionDateStruct":116,"leadSponsor":118,"locationsCount":43},"100613550","early-phase-1-a-phase-01-clinical-trial-with-an-expansion-phase-of-gsk5764227-a-b7-h3-targeted-antibody-drug-conjugate-adc-in-patients-with-recurrent-grade-4-glioma-and-patients-with-brain-metastases-100613550","NCT07268053","A Phase 0\u002F1 Clinical Trial With an Expansion Phase of GSK5764227, a B7-H3-Targeted Antibody-Drug Conjugate (ADC), in Patients With Recurrent Grade 4 Glioma and Patients With Brain Metastases","Inclusion Criteria:\n\n* 1\\. Diagnosed with: (a) GBM according to the 2021 WHO criteria, who have progressed on or following standard of care therapy, including maximal safe resection (biopsy allowed if resection was deemed unsafe) and concurrent chemoradiation; OR (b) Brain metastasis requiring surgical resection, whether treated or untreated, and must have well-controlled systemic disease or NED other than the brain metastases, in the opinion of the patient's primary oncologist.\n* 2\\. Has archival or biopsy brain tumor tissue available.\n* 3\\. Has measurable disease (preoperatively) defined as at least one contrast-enhancing lesion with two perpendicular measurements of at least 1 cm.\n* 4\\. Age ≥18 at time of consent.\n* 5\\. Has a performance status of ≤2 on the ECOG scale.\n* 6\\. Has adequate bone marrow and organ function as defined by the following laboratory values (as assessed by the local laboratory for eligibility):\n* Adequate Bone Marrow Function: Absolute neutrophil count ≥1500\u002FμL (≥1.5 x 109\u002FL), Platelets (at time of surgery) ≥100,000\u002FμL (≥100 x 109\u002FL), Hemoglobin ≥9.0 g\u002FdL or ≥5.6 mmol\u002FL (Criteria must be met without erythropoietin dependency and without pRBC transfusion within prior 2 weeks.)\n* Adequate Hepatic Function: Total Bilirubin ≤1.5x ULN (Participants with Gilbert's syndrome with a total bilirubin \\>1.5x ULN and direct bilirubin ≤1.5x ULN will be permitted.), AST (SGOT) ≤2.5x institutional ULN, ALT (SGPT) ≤2.5x institutional ULN (Participants with liver metastases with ALT ≤5x ULN will be permitted.)\n* Adequate Renal Function: eGFR ≥50 mL\u002Fmin\u002F1.73 m2 (Calculated as individualized eGFR using the CKD-EPI formula \\[2021\\]); If measured or calculated GFR (e.g., creatinine clearance; mGFR) is required or used: ≥60 mL\u002Fmin\n* Adequate Metabolic Function: Albumin ≥2.8 g\u002FdL\n* Adequate Coagulation: INR or PT and aPTT ≤1.5x ULN\n* 7\\. For females of childbearing potential: (a) Must have a confirmed negative serum pregnancy test (β-hCG) before starting study treatment (within 24 hours of first infusion); in rare cases where hCG is suspected to be elevated in the absence of pregnancy (e.g., due to a tumor producing hCG), an ultrasound must be performed to rule out possible pregnancy. (b) Must use a highly effective method of contraception (with a failure rate of \\\u003C1% per year and low user dependency) for at least 28 days prior to treatment, and agree to use such a method during study participation and for an additional 8 months after final study drug administration. (c) Agrees not to breastfeed starting at screening, during study participation, and for 8 months after final study drug administration. (d) Agrees not to donate eggs (ova, oocytes) for the purpose of reproduction starting at screening, during study participation, and for 8 months after final study drug administration.\n* 8\\. For females of non-childbearing potential, is no longer of childbearing potential due to surgical, chemical, or natural menopause.\n* 9\\. For males: (a) Agrees not to donate sperm starting at screening, during study participation, and for 5 months after final study drug administration. (b) Abstains from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long term and persistent basis) and agrees to remain abstinent starting at screening, during study participation, and for 5 months after final study drug administration; OR Must use a male condom and their female partner must use an additional highly effective method of contraception (with a failure rate of \\\u003C1% per year and low user dependency) starting at screening, during study participation, and for 5 months after final study drug administration.\n* 10\\. Agrees to adhere to Lifestyle Considerations throughout study duration.\n* 11\\. Able and willing to comply with scheduled visits, treatment plans, laboratory tests and other procedures.\n* 12\\. Understands the informed consent document and has voluntarily agreed to participate by giving written informed consent (personally or via legally authorized representative(s), and assent if applicable). Written informed consent for the protocol must be obtained prior to any screening procedures. If consent cannot be expressed in writing, it must be formally documented and witnessed, ideally via an independent trusted witness.\n\nExclusion Criteria:\n\n* 1\\. Evidence of leptomeningeal metastasis or spinal cord compression.\n* 2\\. Unable to undergo through MRI of the brain with IV contrast.\n* 3\\. Known active systemic bacterial infection (requiring IV antibiotics or fever \\>38.5°C at time of initiating study treatment), fungal infection, or detectable viral infection (such as known human immunodeficiency virus positivity or with known active hepatitis B or C \\[for example, hepatitis B surface antigen positive\\] (screening of viral infection is not required for enrollment).\n* 4\\. Serious infections within 4 weeks prior to the first infusion of study drug, including but not limited to infectious complications, bacteremia, severe pneumonia treated with IV antibiotics for ≥2 weeks; active infections with therapeutic IV antibiotics within 2 weeks prior to the first infusion of study drug. (Individuals who are receiving or have received prophylactic antibiotics \\[e.g., prophylaxis against urinary infections\\] are allowed).\n* 5\\. Known other concurrent severe psychiatric and\u002For an uncontrolled medical condition that, in the Investigator's judgement, would cause unacceptable safety risks, contraindicate participation in the clinical study, or compromise compliance with the protocol.\n* 6\\. Have any unresolved toxicities from prior therapy greater than NCI-CTCAE v5 Grade 1 at the time of starting study treatment (exceptions include: alopecia, hearing loss, vitiligo, endocrinopathy managed with replacement therapy, Grade 2 neuropathy, and any chronic Grade 2 toxicities following discussion with the Principal Investigator).\n* 7\\. Has received treatment with any of the following:\n* a. Orlotamab, enoblituzumab, I-Dxd, or otherB7-H3 targeted agents.\n* b. Investigational agent within 4 weeks prior to the first infusion of study drug.\n* c. Cytotoxic chemotherapy or anticancer drugs within 14 days prior to the first infusion of study drug.\n* d. Monoclonal antibody within 28 days prior to the first infusion of study drug.\n* e. Immunosuppressive agents within 30 days prior to the first infusion of study drug, or requires long-term (30 days or longer) glucocorticoid therapy. NOTE: A stable or reduced daily dose of 8 mg dexamethasone for management of GBM-related edema and its associated symptoms within 14 days prior to dosing is permitted; however, additional weekly CBC monitoring is required during concomitant administration of dexamethasone with GSK5764227, as outlined in the SoA (see section 1.3). NOTE: Low dose corticosteroids (prednisone ≤10 mg\u002Fday or equivalent) may be administered and use of inhaled or topical steroids and prophylactic corticosteroids for procedures are permitted.\n* f. Strong\u002Fmoderate inhibitors of CYP3A4, CYP2D6, P-gp, or BCRP, within 7 days prior to the first infusion of study drug; or need to continue treatment with these drugs (should be discontinued for at least 14 days prior to the first study infusion).\n* g. Transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including G-CSF, granulocyte-macrophage colony-stimulating factor, or recombinant erythropoietin) with 14 days prior to enrollment.\n* 8\\. Major surgery within 4 weeks prior to the first infusion of study drug that, in the Investigator's judgement, would cause unacceptable safety risks.\n* 9\\. Clinically significant bleeding symptoms or significant bleeding tendency within 1 month prior to the first infusion of study drug.\n* 10\\. Allergy or hypersensitivity to any component of GSK5764227 (ADC, antibody, payload GSK5757810) or its excipients, history of severe allergies (e.g., anaphylactic shock), severe IRRs, or idiosyncrasy to recombinant humanized or mouse proteins.\n* 11\\. History of prior allogenic or autologous bone marrow transplant or other solid organ transplant.\n* 12\\. Has evidence of current ILD or pneumonitis, or history of ILD or noninfectious pneumonitis requiring high-dose glucocorticoids.\n* 13\\. History of moderate to severe lung disease.\n* 14\\. Has serious or poorly controlled hypertension including:\n* a. History of hypertensive crisis.\n* b. Hypertensive encephalopathy.\n* c. Adjustment of antihypertensive medications due to poor blood pressure control within 2 weeks prior to the first infusion of study drug.\n* d. Systolic blood pressure ≥160 mmHg or diastolic blood pressure ≥100 mmHg during screening period.\n* 15\\. Has any of the following cardiac examination abnormalities:\n* a. Evidence of current clinically significant arrhythmias or ECG abnormalities (e.g., complete left bundle branch block, third-degree AV block, second-degree AV block, PR interval \\>250 msec).\n* b. Risk factors of prolonged QTc or arrhythmia events, such as: heart failure, refractory hypokalemia, congenital long QT syndrome, family history of long QT syndrome or unexplained sudden death of any direct relative under 40 years old, or any concomitant medications that prolong the QT interval.\n* c. Has QTc \\>450 msec or \\>480 msec for participants with bundle branch block (QTcF can be machine-calculated or manually over-read).\n* d. Known reduced LVEF fraction \\\u003C50%.\n* 16\\. Has severe, uncontrolled or active cardiovascular disorders, including but not limited to:\n* a. Myocardial infarction within 6 months prior to first infusion of study drug.\n* b. Unstable angina within 6 months prior to the first infusion of study drug, not controlled by standard of care therapy.\n* c. Congestive heart failure (NYHA Class III or IV congestive heart failure) within 6 months prior to the first infusion of study drug.\n* d. Cerebrovascular accident or transient ischemic attack within 6 months prior to the first infusion of study drug.\n* e. History of clinically significant (as determined by the Investigator) atrial arrhythmia, not controlled by standard of care therapy.\n* f. History of clinically significant (as determined by the Investigator) ventricular arrhythmia, or occurrence of any clinically significant ventricular arrhythmia during screening.\n* g. Serious arteriovenous thromboembolic events (such as deep vein thrombosis, pulmonary embolism, etc.) within 3 months prior to the first infusion of study drug (except for implantable venous port, catheter-related thrombosis, or superficial vein thrombosis, which are not considered \"serious\" thromboembolism).\n* 17\\. Known active infectious diseases requiring systemic treatment or known HIV. No active screening needed for active infectious diseases.\n* 18\\. Has documented presence HBsAg, hepatitis B core antibody (HbcAb), or hepatitis B surface antibody (HbsAb) (except for presence of HbsAb attributable to previous vaccination) at screening or within 3 months prior to the first infusion of study intervention.\n* 19\\. Has a positive HCV antibody test result at screening or within 3 months prior to the first infusion of study intervention. NOTE: Participants with a positive HCV antibody test result due to prior resolved disease can be enrolled if a confirmatory negative HCV RNA test is obtained and the participant otherwise meets entry criteria.\n* 20\\. Has a positive HCV RNA test result at screening or within 3 months prior to the first infusion of study intervention. NOTE: The HCV RNA test is optional, and participants with a negative HCV antibody test are not required to undergo HCV RNA testing as well.\n* 21\\. Has cirrhosis or current unstable livery or biliary disease (as determined by the Investigator) defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal\u002Fgastric varices, or persistent jaundice (individuals with stable non-cirrhotic chronic liver disease \\[including Gilbert's syndrome or asymptomatic gallstones\\] or hepatobiliary involvement of malignancy are permitted).\n* 22\\. History of autoimmune disease that has required systemic treatments in the 2 years prior to screening (individuals with prior history of autoimmune disease must be discussed with the Medical Monitor; replacement therapy is not considered a form of systemic therapy \\[e.g., thyroid hormone for autoimmune thyroiditis or insulin is not exclusionary\\]).\n* 23\\. Has any active renal condition (e.g., requirement for dialysis, or any other significant renal condition that could affect the participant's safety \\[renal obstruction successfully managed by stenting is permitted\\]).\n* 24\\. Is unable to adhere to the protocol-defined Schedule of Activities, including requirements for the Follow-up Period of the study, study procedures, restrictions, and requirements as determined by the Investigator.\n* 25\\. Known vaccination or hypersensitivity of any level within 4 weeks prior to the first infusion of study drug.\n* 26\\. Has received any live vaccine within 30 days prior to the first infusion of study drug.\n* 27\\. Is pregnant or breastfeeding.\n* 28\\. Has donated blood or blood products in excess of 500 mL (approximately 1 pint) within 1 month prior to first infusion of study intervention.",{"count":103,"type":20},15,[23],"This will be an open-label Phase 0\u002F1 study that will enroll approximately 15 participants, 9 participants with recurrent WHO Grade 4 glioma (rGBM) and 6 participants with brain metastases, who will receive the investigational drug risvutatug rezetecan (GSK5764227), a B7-H3-targeted antibody-drug conjugate (ADC) with the GSK5757810 payload.\n\nThe trial will consist of a Phase 0 component (subdivided into Arms A and B) and an Expansion Phase 1 component. Participants with tumors demonstrating a positive pharmacokinetic (PK) response in the Phase 0 component will be eligible to enroll in the Expansion Phase to receive therapeutic dosing of risvutatug rezetecan.",[56,107],"Brain Metastasases",[109,110],"ADC","Antibody Drug Conjugate","2026-03-04",{"date":113,"type":35},"2026-03-06",{"date":115,"type":35},"2026-02-11",{"date":117,"type":20},"2029-07",{"name":41,"class":42},""]