Trastuzumab Deruxtecan (T-DXd) for People With Brain Cancer

NCT06058988 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-208
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to find out how much tratuzumab deruxtecan (T-DXd) can penetrate the tumor when injected into the body, and whether T-DXd may be an effective treatment for brain cancers that express the HER2 protein.

Conditions

Brain Cancer; Glioblastoma; Metastatic Cancer; Leptomeningeal Metastasis; Recurrent Glioblastoma

Keywords

Brain Cancer; Glioblastoma; Metastatic Cancer; Leptomeningeal Metastasis; Recurrent Glioblastoma; Trastuzumab Deruxtecan; T-DXd; 22-208; Memorial Sloan Kettering Cancer Center

Outcome Measures

Primary Outcomes (1)

• Intraoperative plasma concentrations in brain tumors after T-DXd injections

  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

  Up to 24 months

Study Arms (3)

Cohort A

EXPERIMENTAL

Participants with Her2-expressing or solid tumors with activating ERBB2 mutations with 1 or more CNS metastases requiring neurosurgical resection/biopsy with no prior T-DXd

Drug: Trastuzumab deruxtecan

Cohort B

EXPERIMENTAL

Participants with Her2-expressing or solid tumors with activating ERBB2 mutations with 1 or more CNS metastases requiring neurosurgical resection/biopsy with no prior T-DXd and prior T-DXd exposure and with documented radiological CNS progression while on T-DXd, requiring neurosurgical resection/biopsy of 1 or more recurrent metastases, with continuation of T-DXd until prior to surgery

Drug: Trastuzumab deruxtecan

Cohort C

EXPERIMENTAL

Participants with recurrent glioblastoma requiring neurosurgical resection/biopsy

Drug: Trastuzumab deruxtecan

Interventions

Trastuzumab deruxtecan DRUG

All participants will receive T-DXd prior to indicated brain tumor resection/biopsy

Also known as: T-DXd

Cohort A; Cohort B; Cohort C

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients ≥ 18 years of age with one or more brain tumors planned for neurosurgical resection/biopsy
• Pathologically-documented glioblastoma; or
• Metastatic cancer that:
• o Has a history of Her2 expression or activating Her2-mutation
• 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

You may not qualify if:

• 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:
• Lung-specific intercurrent clinically significant illnesses including, but not limited to, any underlying pulmonary disorder (e.g. pulmonary emboli within three months of the study enrollment, severe asthma, severe COPD, restrictive lung disease, pleural effusion etc.)
• Any autoimmune, connective tissue or inflammatory disorders (e.g. Rheumatoid arthritis, Sjogren's, sarcoidosis etc.) where there is documented, or a suspicion of pulmonary involvement at the time of screening.
• Prior pneumonectomy (complete)
• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Brain Neoplasms; Glioblastoma; Neoplasm Metastasis; Meningeal Carcinomatosis

Interventions

trastuzumab deruxtecan

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Astrocytoma; Glioma; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Meningeal Neoplasms

Study Officials

• Nelson Moss, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nelson Moss, MD

CONTACT

212-639-7075; mossn@mskcc.org

Shanu Modi, MD

CONTACT

646-888-4564; modis@MSKCC.ORG

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2023
• First Posted: September 28, 2023
• Study Start: September 22, 2023
• Primary Completion (Estimated): September 22, 2027
• Study Completion (Estimated): September 22, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share

Locations

US (1)