[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-studies-list:{\"conditionNormalized\":\"diffuse-midline-glioma-dmg\",\"overallStatus\":[\"RECRUITING\",\"AVAILABLE\",\"NOT_YET_RECRUITING\"],\"orderBy\":\"LastUpdateSubmitDate:desc\",\"size\":25,\"offset\":0}":3,"health-study-condition:diffuse-midline-glioma-dmg":28},{"pageToken":4,"total":5,"offset":6,"count":5,"results":7},null,2,0,[8,51],{"id":9,"slug":10,"hasResults":11,"nctId":12,"briefTitle":13,"officialTitle":14,"acronym":15,"eligibilityCriteria":16,"healthyVolunteers":11,"sex":17,"minAge":18,"maxAge":19,"enrollmentInfo":20,"targetDuration":4,"studyType":23,"phases":24,"briefSummary":26,"conditions":27,"keywords":36,"overallStatus":38,"whyStopped":4,"lastUpdateSubmitDate":39,"lastUpdatePostDateStruct":40,"startDateStruct":43,"completionDateStruct":45,"leadSponsor":47,"locationsCount":50},"100418695","phase-1-onc206-for-treatment-of-newly-diagnosed-recurrent-diffuse-midline-gliomas-and-other-recurrent-malignant-cns-tumors-100418695",false,"NCT04732065","ONC206 for Treatment of Newly Diagnosed, Recurrent Diffuse Midline Gliomas, and Other Recurrent Malignant CNS Tumors","Open Label Phase 1 and Target Validation Study of ONC206 in Children and Young Adults With Newly Diagnosed or Recurrent Diffuse Midline Glioma (DMG), and Other Recurrent Primary Malignant Central Nervous System (CNS) Tumors","PNOC023","Inclusion Criteria:\n\n* ARM A: Children and young adults with DMG, H3K27 altered (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who completed at least one line of prior therapy. Prior treatment must have included focal radiation therapy and patients must be within 4-14 weeks from completion of radiation therapy to registration (patients must start treatment within 1 week from registration), have not started any other therapies post-radiation, and have no evidence of disease progression.\n* ARM A: Tumor tissue confirmation of DMG, H3K27 altered is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM A: Participants must have recovered from all acute side effects of prior therapy.\n* ARM A: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)\n* ARM B: Newly diagnosed children and young adults (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) with a diagnosis of DMG, H3K27 altered are eligible, including spinal cord DMGs.\n* ARM B: Tumor tissue confirmation of DMG is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Children and young adults with DMGs (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression and are recommended to get re-irradiation.\n* ARM C: Patients must have undergone prior focal radiation therapy as part of their initial therapy and should be at least 6 months from prior radiation therapy. If timing is less than 6 months from prior focal radiation, these patients need to be discussed with the study chair(s).\n* ARM C: Tumor tissue confirmation is mandatory and pathology must be consistent with a DMG, H3K27 altered.\n* ARM C: Participants must have recovered from all acute side effects of prior therapy\n* ARM C: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team)\n* ARM D: Children and young adults with recurrent primary malignant CNS tumors, excluding DMGs, (Dose escalation: 2-21 years of age; Dose expansion: 2 years of age and above) who have evidence of progression but have not been treated for this progression. Participants who received a surgical resection for that progression are eligible if surgery has no curative intent. These patients need to be discussed with the study team.\n* ARM D: Prior tumor tissue confirmation is mandatory and pathology from the primary tumor must be consistent with malignant CNS tumor (diagnosis of ependymoma is allowed).Tissue at the time of progression is not required.\n* ARM D: Participants must have recovered from all acute side effects of prior therapy\n* ARM D: From the projected start of scheduled study treatment, the following time periods must have elapsed: 5 half-lives from any investigational agent, 4 weeks from cytotoxic therapy (except 23 days for temozolomide and 6 weeks from nitrosoureas), 4 weeks from antibodies and must be at least 7 days since the completion of therapy with a biologic or small molecule agent. For any biologic or small molecule agent with known adverse events that can occur beyond 7 days after administration, the period prior to enrollment must be beyond the time during which adverse events are known to occur (these should be discussed with the study team). Bevacizumab used for pseudoprogression does not require a wash out period.\n* TARGET VALIDATION: Newly diagnosed children and adults (2 years of age and above) with imaging consistent with a DMG, H3K27 altered are eligible.\n* TARGET VALIDATION: Children and young adults with recurrent primary malignant CNS tumors, including recurrent DMG, (2 years of age and above) who have evidence of progression but have not been treated for this progression.\n* TARGET VALIDATION: Participants must undergo tumor tissue collection as part of their standard of care\n* Participants who are receiving steroids must be on a stable or decreasing dose for at least 3 days prior to registration.\n* Peripheral absolute neutrophil count (ANC) \\>= neutrophil 1.0 g\u002Fl.\n* Platelet count \\>= 100 x 10\\^9\u002FL (transfusion independent, defined as not receiving platelet transfusions for at least 7 days prior to enrollment).\n* Serum creatinine \\\u003C 1.5 Upper Limit normal (ULN) based on age and gender.\n* Total bilirubin \\\u003C= 1.5 x upper limit of normal (ULN) for age; in presence of Gilbert's syndrome, total bilirubin \\\u003C 3 x ULN or direct bilirubin \\\u003C 1.5 x ULN.\n* Alanine aminotransferase (ALT) \\\u003C= 3 x ULN.\n* Aspartate aminotransferase (AST) \\\u003C= 3 x ULN.\n* Patients with seizure disorder may be enrolled if seizure disorder is well controlled\n* The effects of ONC206 on the developing human fetus is unknown. For this reason, females of child-bearing potential and males must agree to use adequate contraception. Adequate methods include: hormonal or barrier method of birth control; or abstinence prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Males treated or enrolled on this protocol must also agree to use adequate contraception prior to the study and for the duration of study participation\n* Karnofsky \\>= 50 for participants \\> 16 years of age and Lansky \\>= 50 for participants =\\\u003C 16 years of age. Participants who are unable to walk because of paralysis, but who are up in a wheelchair, will be considered ambulatory for the purpose of assessing the performance score\n* Participants must be willing to provide adequate tissue. A minimum of 10-20 paraffin embedded unstained slides OR 1 block with tumor content of 40% or greater is required. Frozen tissue is also acceptable. Participants who previously enrolled on PNOC022 and provided adequate tissue, may not need to submit additional tissue - confirm with Study Chairs. Participants who do not meet this criterion may be discussed on a case-by-case basis with the Study Chairs.\n* A legal parent\u002Fguardian or participant must be able to understand, and willing to sign, a written informed consent and assent document, as appropriate\n* Patients must be enrolled on PNOC COMP if PNOC COMP is open to accrual at the enrolling institution\n\nExclusion Criteria:\n\n* Arm A \\& B: For tumors that do not have a pontine or spinal cord epicenter the following specific exclusion criteria apply: Thalamic DMG and cerebellar, H3K27 altered that has undergone standard radiation without concurrent therapy (other than temozolomide).\n* Arm C \\& D: Patients who participated in trials investigating ONC201 in the upfront setting will not be eligible. Prior ONC201 exposure as part of PNOC022 or expanded access programs will be allowed.\n* Participants who are currently receiving another investigational drug are not eligible.\n* Participants who are currently receiving other anti-cancer agents are not eligible.\n* Participants with a known disorder that affects their immune system, such as human immunodeficiency virus (HIV) or hepatitis B or C, or an auto-immune disorder requiring systemic cytotoxic or immunosuppressive therapy are not eligible. Note: Participants that are currently using inhaled, intranasal, ocular, topical or other non-oral or non-intravenous (IV) steroids are not necessarily excluded from the study but need to be discussed with the study chair.\n* Participants with uncontrolled infection.\n* Female participants of childbearing potential must not be pregnant or breast-feeding. Female participants of childbearing potential must have a negative serum or urine pregnancy test prior to the start of therapy.\n* Active illicit drug use or diagnosis of alcoholism.\n* History of allergic reactions attributed to compounds of similar chemical or biologic composition to ONC206.\n* Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant or family.\n* Any participants with illnesses that may affect absorption of ONC206.\n* Any participants on strong inhibitors or inducers of CYP3A4, 2D6, 1A2, 2C9 and 2C19 at least 14 days prior and throughout the study.","ALL","2 Years","21 Years",{"count":21,"type":22},208,"ESTIMATED","INTERVENTIONAL",[25],"PHASE1","This phase I trial studies the effects and best dose of ONC206 alone or in combination with radiation therapy in treating patients with diffuse midline gliomas that is newly diagnosed or has come back (recurrent) or other recurrent primary malignant CNS tumors. ONC206 is a recently discovered compound that may stop cancer cells from growing. This drug has been shown in laboratory experiments to kill brain tumor cells by causing a so called \"stress response\" in tumor cells. This stress response causes cancer cells to die, but without affecting normal cells. ONC206 alone or in combination with radiation therapy may be effective in treating newly diagnosed or recurrent diffuse midline gliomas and other recurrent primary malignant CNS tumors.",[28,29,30,31,32,33,34,35],"Diffuse Midline Glioma (DMG)","Glioblastoma","Recurrent Ependymoma","Recurrent Malignant Central Nervous System Neoplasm","Spinal Cord Glioma","World Health Organization (WHO) Grade III Glioma","CNS Tumor","Central Nervous System Tumor",[37],"H3 K27M-Mutant","RECRUITING","2026-06-08",{"date":41,"type":42},"2026-06-11","ACTUAL",{"date":44,"type":42},"2021-08-23",{"date":46,"type":22},"2027-07-31",{"name":48,"class":49},"Sabine Mueller, MD, PhD","OTHER",7,{"id":52,"slug":53,"hasResults":11,"nctId":54,"briefTitle":55,"officialTitle":56,"acronym":4,"eligibilityCriteria":57,"healthyVolunteers":11,"sex":17,"minAge":58,"maxAge":59,"enrollmentInfo":60,"targetDuration":4,"studyType":23,"phases":62,"briefSummary":63,"conditions":64,"keywords":4,"overallStatus":67,"whyStopped":4,"lastUpdateSubmitDate":68,"lastUpdatePostDateStruct":69,"startDateStruct":71,"completionDateStruct":73,"leadSponsor":75,"locationsCount":78},"100627931","phase-1-a-phase-i-study-of-fz-ad005-in-patients-with-high-grade-glioma-hgg-100627931","NCT07455045","A Phase I Study of FZ-AD005 in Patients With High-Grade Glioma (HGG)","An Open-Label, Multicenter, Phase I Study of FZ-AD005 Antibody-Drug Conjugate in Patients With Recurrent\u002FRefractory High-Grade Glioma (HGG)","Inclusion Criteria:\n\n1. Voluntarily signed Informed Consent Form;\n2. Age 18-70 years, both male and female;\n3. Patients must be able to provide tumor tissue samples (archived tumor tissue within 2 years \\[maximum 5 years\\] or fresh core needle biopsy specimen, if possible) for DLL3 testing, with positive assessment results;\n4. Histopathologically confirmed high-grade glioma, classified according to WHO CNS5 2021 criteria, meeting one of the following characteristics:\n\n   Group A (Post-radiotherapy maintenance phase): Diffuse midline glioma (DMG), with H3 K27 alterated by CLIA-certified laboratory; Patients must be in the maintenance treatment phase following new diagnosis and completion of standard first-line radiotherapy; Group B (Recurrent or progressive high-grade glioma): Recurrent or progressive high-grade glioma (WHO CNS5 Grade 3-4). Including but not limited to: IDH wild-type glioblastoma (GBM), IDH-mutant astrocytoma (Grade 3-4), IDH-mutant oligodendroglioma (Grade 3), etc. (Note: Recurrent or progressive DMG patients may be enrolled in this group during dose escalation phase);\n5. Prior treatment status:\n\n   Group A (Post-radiotherapy maintenance phase): Must have completed standard radiotherapy, with enrollment occurring within 2-6 weeks after radiotherapy completion, and no definitive evidence of progressive disease (PD) on post-radiotherapy imaging; Group B (Recurrent or progressive high-grade glioma): Must be recurrent or refractory patients who have failed standard treatment: must have received at least one prior line of standard treatment (including radiotherapy and\u002For chemotherapy, such as temozolomide), with an imaging evidence of PD; for patients with prior radiotherapy, disease progression must occur \\>12 weeks after radiotherapy, or must be histopathologically confirmed as tumor recurrence rather than necrosis\u002Fpseudoprogression by radiotherapy;\n6. At least one measurable lesion at baseline (RANO 2.0 )\n7. Karnofsky Performance Status (KPS) score ≥70 (if patient has slightly lower score solely due to stable focal neurological deficits but can maintain basic daily living with support, 60 is approval);\n8. If patient is receiving corticosteroids for tumor-related cerebral edema or neurological symptoms, dosage must be stable or decreasing for at least 7 days prior to baseline MRI, with dose ≤5 mg\u002Fday dexamethasone (or equivalent dose of other corticosteroids); if increased steroid dosage is required during screening to control cerebral edema due to clinical deterioration, the patient is ineligible;\n9. Estimated life expectancy ≥12 weeks;\n10. Normal coagulation function, with no risk of active bleeding;\n11. Cardiopulmonary function: Left ventricular ejection fraction (LVEF) ≥50%; pulse oxygen saturation (SpO2) ≥95% on room air at rest, with no dyspnea at rest;\n12. Bone marrow reserve and organ function must meet the following requirements:\n\n    Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹\u002FL, platelets ≥100×10⁹\u002FL, hemoglobin ≥90 g\u002FL (without transfusion, erythropoietin \\[EPO\\], granulocyte colony-stimulating factor \\[G-CSF\\], or other medical supportive treatment within 14 days prior to screening); Coagulation: For subjects not receiving anticoagulation therapy, prothrombin time international normalized ratio (INR) and activated partial thromboplastin time (APTT) ≤1.5×upper limit of normal (ULN) (Note: Subjects receiving stable anticoagulation therapy are allowed if parameters are within therapeutic range and no bleeding risk); Liver: Total serum bilirubin ≤1.5×ULN, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN; if Gilbert's syndrome (unconjugated hyperbilirubinemia) is confirmed, total bilirubin ≤3.0×ULN; AST and ALT ≤3×ULN; Kidney: Serum creatinine (Scr) ≤1.5×ULN, or creatinine clearance (Ccr) ≥50 mL\u002Fmin (calculated by Cockcroft and Gault formula);\n13. All acute toxicities from prior antitumor therapy or surgical procedures must have resolved to baseline severity or NCI CTCAE Version 6.0 Grade ≤1;\n14. Within 7 days prior to enrollment, women of childbearing potential must have negative serum or urine pregnancy test; male and female subjects must agree to use effective contraception (e.g., oral contraceptives, intrauterine device, abstinence, or barrier contraception with spermicide) during study drug administration and for 6 months after the last dose;\n15. Good compliance.\n\nExclusion Criteria:\n\n1. Prior treatment with other anti-DLL3 targeted antibody therapies or other DLL3-directed treatments, or ADC drugs containing DXd payload;\n2. History of allergic reaction to exatecan or ≥Grade 3 gastrointestinal toxicity following prior exatecan use, or hypersensitivity to protein components structurally similar to FZ-AD005, or hypersensitivity to excipients of the FZ-AD005 investigational drug;\n3. Subjects with any contraindications to magnetic resonance imaging (MRI) (e.g., cardiac pacemaker, non-removable metal implants, etc.);\n4. History of other malignancies within the past 3 years (except for specific low-risk tumors that have been radically treated);\n5. Failure to meet the following washout period requirements prior to first dose:\n\n   Chemotherapy (non-nitrosourea), small molecule targeted therapy: ≤3 weeks (21 days) or 5 half-lives (whichever is longer); Nitrosoureas (e.g., lomustine) or mitomycin C: ≤6 weeks (42 days); Immune checkpoint inhibitors (ICI), antibody drugs (including other ADCs): ≤4 weeks (28 days) or 5 half-lives (whichever is longer); Anti-angiogenic therapy (e.g., bevacizumab): ≤5 weeks (35 days); Radiotherapy: For Treatment Group B: whole brain or involved-field radiotherapy ≤12 weeks; palliative radiotherapy (non-intracranial target lesions) ≤2 weeks (Note: For Treatment Group A subjects, standard first-line radiotherapy prior to this enrollment is not subject to this 12-week restriction, but must meet the specific window requirement for time since radiotherapy completion as stated in the inclusion criteria);\n6. Receipt of live vaccine within 4 weeks prior to first dose;\n7. Active infection requiring drug intervention within 2 weeks prior to first dose, or unexplained fever \\>38°C with elevated procalcitonin results between screening and first dose (subjects with tumor-related fever may be enrolled at investigator's discretion);\n8. Severe mass effect or risk of brain herniation, defined as: baseline MRI showing midline shift \\>5 mm, or signs of uncontrolled intracranial hypertension\u002Fhydrocephalus; or investigator's judgment that the patient cannot tolerate any degree of treatment-induced cerebral edema;\n9. Extracranial metastases or diffuse leptomeningeal disease confirmed by imaging (MRI)\u002Fcerebrospinal fluid (CSF) cytology;\n10. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage despite appropriate intervention;\n11. History of (non-infectious) interstitial lung disease (ILD)\u002Fpneumonitis requiring steroid treatment, or current ILD\u002Fpneumonitis, or suspected ILD\u002Fpneumonitis that cannot be excluded by imaging at screening;\n12. Serious cardiovascular or cerebrovascular disease or history (including but not limited to the following):\n\n    Myocardial infarction or unstable angina within 6 months prior to first dose; Congestive heart failure with cardiac function ≥Grade II (NYHA classification); Uncontrolled hypertension (systolic blood pressure \\>160 mmHg or diastolic blood pressure \\>100 mmHg); Baseline QTcF \\>450 ms (male) or \\>470 ms (female); Clinically significant arrhythmia or conduction block requiring drug treatment;\n13. Other serious systemic diseases, including but not limited to diabetes mellitus not effectively controlled;\n14. Subjects with poorly healing wounds, ulcers, or fractures;\n15. Patients who underwent major surgery or serious trauma within 4 weeks prior to first dose;\n16. Receipt of autologous organ or stem cell transplantation within 3 months prior to first dose, or allogeneic organ (except corneal transplantation) or stem cell transplantation within 6 months prior to first dose;\n17. Hepatitis B surface antigen (HBsAg) positive with HBV DNA \\>2000 IU\u002FmL or 10⁴ copies\u002FmL. If HBsAg positive but with low DNA, should receive antiviral treatment according to local treatment guidelines and be willing to receive antiviral treatment throughout the study period; Hepatitis C antibody positive with HCV RNA above the upper limit of normal of the study center;\n18. Active tuberculosis, active syphilis, history of immunodeficiency, positive human immunodeficiency virus (HIV) antibody, or other immunodeficiency diseases;\n19. Requirement for systemic corticosteroids (\\>5 mg\u002Fday dexamethasone or equivalent dose of similar drugs) or other immunosuppressants for systemic treatment within 2 weeks prior to first dose or during the study; Note: Topical and inhaled corticosteroids with minimal systemic absorption are permitted; corticosteroids ≤5 mg\u002Fday dexamethasone (or equivalent dose) for physiological replacement therapy or treatment of tumor-related symptoms are permitted, provided the subject has stable or decreasing dosage for at least 7 days prior to baseline MRI; short-term (≤7 days) corticosteroids for prophylaxis (e.g., contrast allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity due to contact allergens) are permitted;\n20. Definite history of mental illness;\n21. Known history of psychoactive substance abuse, alcoholism, or drug addiction;\n22. Pregnant or lactating women;\n23. Uncontrolled seizures (seizure within 14 days prior to enrollment or requirement for increased antiepileptic drug dosage);\n24. Clinically significant intracranial hemorrhage (\\>Grade 1 acute\u002Fsubacute hemorrhage);\n25. Any other condition that the investigator considers unsuitable for participation in this clinical study.","18 Years","70 Years",{"count":61,"type":22},40,[25],"An Open Label, Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Preliminary Antitumor Activity of FZ-AD005 in Patients with HGG, especially in DMG and other Recurrent HGG.",[65,28,66],"High Grade Glioma (III or IV)","Glioblastoma (GBM)","NOT_YET_RECRUITING","2026-03-02",{"date":70,"type":42},"2026-03-06",{"date":72,"type":22},"2026-03-01",{"date":74,"type":22},"2028-06-01",{"name":76,"class":77},"Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.","INDUSTRY",1]