High Grade Glioma (III or IV)Phase 1NCT07455045
A Phase I Study of FZ-AD005 in Patients With High-Grade Glioma (HGG)
A Phase 1 study testing FZ-AD005 in people with High Grade Glioma (III or IV) and Diffuse Midline Glioma (DMG), run by Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. at 1 site in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- High Grade Glioma (III or IV), Diffuse Midline Glioma (DMG), Glioblastoma (GBM)
- What is being tested?
- FZ-AD005
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 40 participants
- Where
- 1 siteChina
- Study dates
- 1 Mar 2026to 1 Jun 2028
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Voluntarily signed Informed Consent Form;
- Age 18-70 years, both male and female;
- 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;
- Histopathologically confirmed high-grade glioma, classified according to WHO CNS5 2021 criteria, meeting one of the following characteristics:
- 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);
- Prior treatment status:
Show all 18Show fewer
- 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/or 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/pseudoprogression by radiotherapy;
- At least one measurable lesion at baseline (RANO 2.0 )
- 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);
- 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/day 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;
- Estimated life expectancy ≥12 weeks;
- Normal coagulation function, with no risk of active bleeding;
- Cardiopulmonary function: Left ventricular ejection fraction (LVEF) ≥50%; pulse oxygen saturation (SpO2) ≥95% on room air at rest, with no dyspnea at rest;
- Bone marrow reserve and organ function must meet the following requirements:
- Hematology: Absolute neutrophil count (ANC) ≥1.5×10⁹/L, platelets ≥100×10⁹/L, hemoglobin ≥90 g/L (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/min (calculated by Cockcroft and Gault formula);
- All acute toxicities from prior antitumor therapy or surgical procedures must have resolved to baseline severity or NCI CTCAE Version 6.0 Grade ≤1;
- 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;
- Good compliance.
Who cannot join
- Prior treatment with other anti-DLL3 targeted antibody therapies or other DLL3-directed treatments, or ADC drugs containing DXd payload;
- 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;
- Subjects with any contraindications to magnetic resonance imaging (MRI) (e.g., cardiac pacemaker, non-removable metal implants, etc.);
- History of other malignancies within the past 3 years (except for specific low-risk tumors that have been radically treated);
- Failure to meet the following washout period requirements prior to first dose:
- 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);
Show all 27Show fewer
- Receipt of live vaccine within 4 weeks prior to first dose;
- 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);
- Severe mass effect or risk of brain herniation, defined as: baseline MRI showing midline shift >5 mm, or signs of uncontrolled intracranial hypertension/hydrocephalus; or investigator's judgment that the patient cannot tolerate any degree of treatment-induced cerebral edema;
- Extracranial metastases or diffuse leptomeningeal disease confirmed by imaging (MRI)/cerebrospinal fluid (CSF) cytology;
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring repeated drainage despite appropriate intervention;
- History of (non-infectious) interstitial lung disease (ILD)/pneumonitis requiring steroid treatment, or current ILD/pneumonitis, or suspected ILD/pneumonitis that cannot be excluded by imaging at screening;
- Serious cardiovascular or cerebrovascular disease or history (including but not limited to the following):
- 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;
- Other serious systemic diseases, including but not limited to diabetes mellitus not effectively controlled;
- Subjects with poorly healing wounds, ulcers, or fractures;
- Patients who underwent major surgery or serious trauma within 4 weeks prior to first dose;
- 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;
- Hepatitis B surface antigen (HBsAg) positive with HBV DNA >2000 IU/mL or 10⁴ copies/mL. 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;
- Active tuberculosis, active syphilis, history of immunodeficiency, positive human immunodeficiency virus (HIV) antibody, or other immunodeficiency diseases;
- Requirement for systemic corticosteroids (>5 mg/day 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/day 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;
- Definite history of mental illness;
- Known history of psychoactive substance abuse, alcoholism, or drug addiction;
- Pregnant or lactating women;
- Uncontrolled seizures (seizure within 14 days prior to enrollment or requirement for increased antiepileptic drug dosage);
- Clinically significant intracranial hemorrhage (>Grade 1 acute/subacute hemorrhage);
- Any other condition that the investigator considers unsuitable for participation in this clinical study.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site
Sun Yat-Sen University Cancer Center
Guangzhou, Guangdong
ZHENGZHENG GUO, 021-58953355, mlzhou@fd-zj.com
About this study
Official title: An Open-Label, Multicenter, Phase I Study of FZ-AD005 Antibody-Drug Conjugate in Patients With Recurrent/Refractory High-Grade Glioma (HGG)
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.
- Being tested
- FZ-AD005
- Medical subject headings
- Glioma, Glioblastoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FZ-AD005Drug
Every 21 days for 1 cycle. Subjects will receive an intravenous infusion of FZ-AD005 until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study.
| Study group | Role | What they receive |
|---|---|---|
| FZ-AD005 | Experimental | Not described Receives: Drug: FZ-AD005 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum Tolerable Dose (MTD)
To determine the maximum tolerated dose (MTD) and/or recommended doses for expansion (RDEs). RDEs will not exceed MTD.
Measured: Screening up to study completion, assessed up to 36 months
The dose limiting toxicity ( DLT)
To determine the dose limiting toxicities (DLTs) of FZ-AD005
Measured: 21 Days (first cycle)
Adverse Events (AEs）
To check the numbers of AEs happened during the course of trial.
Measured: Screening up to study completion, assessed up to 36 months
Disease control rate(DCR)
To evaluate the [Complete Response (CR) + Partial Response (PR)+ Stable Disease] of FZ-AD005 according to RANO 2.0
Measured: Up to 36 months
Secondary outcomes (10)
Objective Response Rate (ORR)
To evaluate the objective response rate (ORR) [Complete Response (CR) + Partial Response (PR)] of FZ-AD005 according to RANO 2.0
Measured: Up to 12 months
Progression free survival(PFS)
Progression-free survival (PFS) was defined as the interval from the first dose start date to the date of disease progression defined as documented progressive disease (PD) or death from any cause, whichever occurs first.
Measured: Up to 36 months
Duration of Response(DOR)
Duration of Response was defined as the duration of overall response measured from the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented (taking as reference for progressive disease the smallest measurements recorded since the treatment started).
Measured: Up to 36 months
Overall Survival (OS)
overall survival was defined as the time from the date of the first dose start date to the date of death due to any cause
Measured: Up to 36 months
Anti Drug Antibody (ADA)
To check the" Anti Drug Antibody" develops in participants against the FZ-AD005 through blood sample
Measured: Up to 36 months
Time to peak (Tmax)
To measure the time to reach the maximum contraction of Total Antibody, Free DXd and FZ-AD005 in study participants
Measured: Up to 18 weeks
Terminal elimination half-life (t1/2)
To measure the time of Total Antibody, Free DXd and FZ-AD005 will take to eliminate half of it's concentration from participants.
Measured: Up to 18 weeks
Maximum observed plasma concentration (Cmax)
To measure the maximum concentration participants obtained of Total Antibody, Free DXd and FZ-AD004 in their blood plasma.
Measured: Up to 18 weeks
Area under the concentration-time curve (AUC 0-∞) from time 0 to infinity
To measure the drug profile for absorption, distribution, metabolism and excretion for Total Antibody, Free DXd and FZ-AD005 in participants blood plasma
Measured: Up to 18 weeks
Time to Cmax (Tmax)
To measure the time to reach the maximum contraction of Total Antibody, Free DXd and FZ-AD005 in study participants
Measured: Up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2026
- Study start1 Mar 2026 (estimated)
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Jun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for High Grade Glioma (III or IV)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07455045
- Sponsor's protocol ID
- F0041-102
- Status last verified
- Feb 2026
- First submitted
- 2 Mar 2026
- Last updated
- 6 Mar 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-Label, Multicenter, Phase I Study of FZ-AD005 Antibody-Drug Conjugate in Patients With Recurrent/Refractory High-Grade Glioma (HGG)
- ClinicalTrials.gov ID
- NCT07455045
- Acronym / sponsor ID
- F0041-102
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd.Industry (pharma, biotech, devices)
- Study start
- 1 Mar 2026 (estimated)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Jun 2028 (estimated)
- First posted
- 6 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| FZ-AD005 | Experimental | Drug: FZ-AD005 |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Voluntarily signed Informed Consent Form;
- Age 18-70 years, both male and female;
- 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;
- Histopathologically confirmed high-grade glioma, classified according to WHO CNS5 2021 criteria, meeting one of the following characteristics:
- 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);
Key exclusion criteria (27 listed)
- Prior treatment with other anti-DLL3 targeted antibody therapies or other DLL3-directed treatments, or ADC drugs containing DXd payload;
- 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;
- Subjects with any contraindications to magnetic resonance imaging (MRI) (e.g., cardiac pacemaker, non-removable metal implants, etc.);
- History of other malignancies within the past 3 years (except for specific low-risk tumors that have been radically treated);
- Failure to meet the following washout period requirements prior to first dose:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FZ-AD005Every 21 days for 1 cycle. Subjects will receive an intravenous infusion of FZ-AD005 until confirmed progression, unaccepted toxicity, or any criterion for withdrawal from the study. | Drug | FZ-AD005 |
Primary outcome
Maximum Tolerable Dose (MTD)
Time frame: Screening up to study completion, assessed up to 36 months
To determine the maximum tolerated dose (MTD) and/or recommended doses for expansion (RDEs). RDEs will not exceed MTD.
The dose limiting toxicity ( DLT)
Time frame: 21 Days (first cycle)
To determine the dose limiting toxicities (DLTs) of FZ-AD005
Adverse Events (AEs）
Time frame: Screening up to study completion, assessed up to 36 months
To check the numbers of AEs happened during the course of trial.
Disease control rate(DCR)
Time frame: Up to 36 months
To evaluate the [Complete Response (CR) + Partial Response (PR)+ Stable Disease] of FZ-AD005 according to RANO 2.0
10 secondary outcomes
Objective Response Rate (ORR)
Time frame: Up to 12 months
Progression free survival(PFS)
Time frame: Up to 36 months
Duration of Response(DOR)
Time frame: Up to 36 months
Overall Survival (OS)
Time frame: Up to 36 months
Anti Drug Antibody (ADA)
Time frame: Up to 36 months
Time to peak (Tmax)
Time frame: Up to 18 weeks
Terminal elimination half-life (t1/2)
Time frame: Up to 18 weeks
Maximum observed plasma concentration (Cmax)
Time frame: Up to 18 weeks
Area under the concentration-time curve (AUC 0-∞) from time 0 to infinity
Time frame: Up to 18 weeks
Time to Cmax (Tmax)
Time frame: Up to 18 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Mar 2026.
Related trials for High Grade Glioma (III or IV)
RecruitingObservational study
Leica Microsystems Sponsored PMCF Study to Collect and Confirm Clinical Data on the Performance of the GLOW400 Device When Used in Accordance With Its Intended Use
Suspected Grade III and IV Gliomas Requiring Surgical Intervention, Neurosurgical Procedure
RecruitingPhase 1
A Study of RNA-lipid Particle (RNA-LP) Vaccines for Newly Diagnosed Pediatric High-Grade Gliomas (pHGG) and Adult Glioblastoma (GBM)
Adult Glioblastoma, High Grade Glioma
RecruitingPhase 3
5-Aminolevulinic Acid for Photodynamic Diagnosis of Malignant Glioma
5-aminolevulinic Acid, Fluorescence-guided Resection
Not yet recruitingPhase 2
Study of Tovorafenib in High-Grade Glioma and Diffuse Intrinsic Pontine Glioma (DIPG)
High Grade Glioma (HGG) of the Brain With BRAF Aberration, High Grade Glioma (III or IV)
Active, not recruitingPhase 1
Safety and Efficacy Study for DC Vaccine in Recurrent or Progressive High-grade Gliomas
WHO Grade III Gliomas, WHO Grade IV Gliomas
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing FZ-AD005 in people with High Grade Glioma (III or IV) and Diffuse Midline Glioma (DMG), run by Shanghai Fudan-Zhangjiang Bio-Pharmaceutical Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 27 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 6 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Mengli zhou (00-86-021-58953355, mlzhou@fd-zj.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum Tolerable Dose (MTD) (time frame: Screening up to study completion, assessed up to 36 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Mar 2026.