Trastuzumab Deruxtecan (T-DXd) for Brain Cancer
This study is looking at a drug called trastuzumab deruxtecan (T-DXd) for people with brain cancer, including glioblastoma and metastatic cancer that has spread to the brain. The main goal is to see how much of the T-DXd drug gets into brain tumors when it's given before surgery or biopsy. Researchers also want to know if T-DXd could be an effective treatment for brain cancers that have a specific protein called HER2. You might be able to join if you are an adult (18 or older) with a brain tumor that needs surgery or a biopsy, and your cancer has certain HER2 levels. The study plans to enroll 30 participants, but its current recruitment status is unclear.
- Study design
- This is an interventional study where all 30 participants will receive the drug trastuzumab deruxtecan (T-DXd).
- What's involved
- You would receive trastuzumab deruxtecan (T-DXd) before your planned brain tumor surgery or biopsy.
- Compensation
- Not stated in the trial record.
- Follow-up
- Plasma concentrations in brain tumors will be measured for up to 24 months.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT06058988
Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer
Recruiting
PHASE2Ages 18+InterventionalTreatmentMemorial Sloan Kettering Cancer CenterInvestigator-initiated
~30 participants
Updated 2026-02-23 on ClinicalTrials.gov
What's tested:Trastuzumab deruxtecan
At a glance
Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Intraoperative plasma concentrations in brain tumors after T-DXd injections
Measured over Up to 24 months
Conditions
Where it's being run
1 sites across 1 statesNew York1
Study leadership
- Nelson Moss, MD · PRINCIPAL_INVESTIGATOR · Memorial Sloan Kettering Cancer Center
Who to contact
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Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Adult patients ≥ 18 years of age with one or more brain tumors planned for neurosurgical resection/biopsy
Pathologically-documented glioblastoma; or
Metastatic cancer that:
Her2+ defined as 3+ on IHC
Her2-low defined as IHC1+ or 2+ and ISH- according to ASCO-CAP 2018 Her2 testing guidelines52
Her2 mutations must be described to be activating, occur at a known hotspot (e.g. exon 20 insertions, S310, G660, R678, L755, D769, L777), or involve the transmembrane, juxtamembrane or tyrosine kinase domains
Other untreated brain tumors (and prior radiation, including whole-brain and/or stereotactic radiation) are allowed
Patients with concomitant leptomeningeal metastasis are eligible provided they have parenchymal brain neoplastic disease requiring resection/biopsy
Prior treatments:
Cohort A: Brain parenchymal metastases in patients with Her2-expressing/ERBB2- activating-mutant cancer with no prior T-DXd exposure (T-DXd naïve)
Cohort B: Brain parenchymal metastases in patients with Her2-expressing/ERBB2- activating-mutant cancer with prior T-DXd exposure
Cohort C: Recurrent glioblastoma
For all cohorts: no limit on prior CNS radiation or systemic therapy, including Her2- targeting antibody therapy (including trastuzumab, pertuzumab, trastuzumab emtansine)
KPS ≥ 60 Or ECOG \< 2
Life expectancy \>12 weeks
Left ventricular ejection fraction ≥50%
Adequate bone marrow, renal, hepatic, and coagulation parameters (obtained ≤7 days prior to the first day of study treatment):
Absolute neutrophil count (ANC) ≥1.5 × 103/μL (granulocyte-colony stimulating factor administration is not allowed within 1 week prior to C1D1)
Platelet count ≥10.0x104/μL. Note: Participants requiring ongoing transfusions or growth factor support to maintain platelet count ≥10.0x104/μL are not eligible. (Platelet transfusion is not allowed within 1 week prior to C1D1)
Hemoglobin ≥ 8.0 g/dL. Note: Participants requiring ongoing transfusions or growth factor support to maintain hemoglobin ≥8.0 g/dL are not eligible (\> 8 g/dL in gastric cancer / gastroesophageal cancer indications). (Red blood cell transfusion is not allowed within 1 week prior to C1D1)
Serum albumin ≥ 2.5 g/dL
Creatinine clearance ≥30 mL/min, as calculated using the Cockcroft-Gault equation
Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤3 × upper limit of normal (ULN) (\<5x ULN in participants with liver metastases)
Total bilirubin ≤1.5 × ULN) if no liver metastases or \<3 × ULN in the presence of documented Gilbert's syndrome (unconjugated hyperbilirubinemia) or liver metastases at baseline
International normalized ratio (INR) and activated partial thromboplastin time (aPTT) ≤1.0xULN unless on medication known to reversibly alter INR and/or aPTT
Evidence of post-menopausal status or negative serum pregnancy test for females of childbearing potential who are sexually active with a non-sterilized male partner. For women of childbearing potential, a negative result for serum pregnancy test (test must have a sensitivity of at least 25 mIU/mL) must be available within 7 days of the screening visit and urine beta-human chorionic gonadotropin (β-HCG) pregnancy test prior to each administration of T-DXd.
Women of childbearing potential are defined as those who are not surgically sterile (i.e.
Female patients of childbearing potential who are sexually active with a non-sterilized male partner must use at least one highly effective method of contraception, presented in Table 1 from the time of screening and must agree to continue using such precautions for 7 months after the last dose of T-DXd. Note: estrogen/progesterone is contraindicated in ER+ breast cancer, and in other cancers could increase the risk of DVT. Female patients must refrain from breastfeeding while on study and for 7 months after the last dose of T-DXd.
Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to 4 months after the final dose ofT-DXd. Complete heterosexual abstinence for the drug washout period is an acceptable contraceptive method if it is in line with the patient's usual lifestyle (consideration must be made to the duration of the clinical trial); however, periodic or occasional abstinence, the rhythm method, and the withdrawal method are not acceptable. It is strongly recommended for the female partners of a male patient to also use ≥1 highly effective method of contraception throughout this period, as described in Table 1. In addition, male patients should refrain from fathering a child, or freezing or donating sperm from the time of enrollment until 4 months after the last dose of T-DXd; sperm preservation should be considered prior to enrollment in this study.
Female subjects must not donate, or retrieve for their own use, ova from the time of enrollment through at least 7 months after the final study drug administration. Preservation of ova may be considered prior to enrollment in this study.
Adequate treatment washout period from prior therapies to allow recovery from any prior treatment-related toxicities before enrollment in the judgment of the Investigator.
Total heterosexual abstinence (evaluate in relation to the duration of the clinical study and the preferred and usual lifestyle choice of the participant)
Vasectomised sexual partner (if partner is the sole sexual partner of the trial participant and that the vasectomised partner has received medical assessment of the surgical success)
Bilateral tubal occlusion
Intrauterine device (provided coils are copper banded)
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (noting relevant contraindications in ER+ breast cancer, and risk of DVT in other cancers)
oral
intravaginal
transdermal
Progestogen-only hormonal contraception associated with inhibition of ovulation
oral
injectable
implantable
Intrauterine hormone-releasing system (IUS)
Exclusion
Contraindication or history of allergic reaction to T-DXd
Significant comorbidities as per investigator evaluation
Inability to comply with protocol and/or unwilling or not available for follow up assessments or any condition which in the investigator's opinion makes the patient unsuitable for study participation
Ferrous or other contraindication to MR imaging
History of myocardial infarction within 6 months before enrollment
History of symptomatic congestive heart failure (New York Heart Association Class II to IV)
Corrected QT interval (QTc) prolongation to \>470 ms (females) or \>450 ms (male) based on12-lead electrocardiogram (ECG)
Subjects with troponin levels above ULN at screening (as defined by the manufacturer), and without any myocardial related symptoms, should have a cardiologic consultation before enrollment to rule out MI
History of (noninfectious) interstitial lung disease (ILD)/pneumonitis that required steroids, has current ILD/pneumonitis, or where suspected ILD/pneumonitis can not be ruled out by baseline chest CT at Screening.
Lung criteria:
Uncontrolled infection requiring IV antibiotics, antivirals, or antifungals
Active primary immunodeficiency, known human immunodeficiency virus (HIV) infection, or active hepatitis B or C infection. Patients positive for hepatitis C (HCV) antibody are eligible only if polymerase chain reaction is negative for HCV RNA.
Receipt of live, attenuated vaccine (mRNA and replication deficient adenoviral vaccines are not considered attenuated live vaccines) within 30 days prior to the first dose of trastuzumab deruxtecan. Note: Patients, if enrolled, should not receive live vaccine during the study and up to 30 days after the last dose of T-DXd.
Has unresolved toxicities from previous anticancer therapy, defined as toxicities (other than alopecia) not yet resolved to Grade ≤ 1 or baseline. Note: Subjects may be enrolled with chronic, stable Grade 2 toxicities (defined as no worsening to \>Grade 2 for at least 3 months prior to \[randomization/enrollment/Cycle 1 Day 1\] and managed with standard of care treatment) that the investigator deems related to previous anticancer therapy, such as:
Known allergy or hypersensitivity to study treatment or any of the study drug excipients. For patients who are allergic to gadolinium-based agents may receive premedication as per institutional protocol or imaged without contrast at the discretion of the Principal Investigator; reactions will be managed per standard institutional protocol
History of severe hypersensitivity reactions to other monoclonal antibodies
Pregnant or breastfeeding female patients, or patients who are planning to become pregnant.
Patients with substance abuse or any other medical conditions such as clinically significant cardiac or psychological conditions, that may, in the opinion of the investigator, interfere with the subject's participation in the clinical study or evaluation of the clinical study results.
Multiple primary malignancies within 3 years, with the exception of:
A pleural effusion, ascites or pericardial effusion that requires drainage, peritoneal shunt, or Cell-free and Concentrated Ascites Reinfusion Therapy (CART)
What this trial measures
- Intraoperative plasma concentrations in brain tumors after T-DXd injectionsUp to 24 months
To evaluate the brain tumor penetration of trastuzumab deruxtecan (T-DXd) and its payload (DXd) in Her2+/Her2-low/Her2-mutant brain metastases and of Her2-expressing glioblastoma. Concentrations will be presented as brain tumor:plasma ratios across brain lesions, using intraoperative plasma concentrations