A Window of Opportunity Study of Patritumab Deruxtecan in Patients With Brain Metastases

NCT05620914 | Withdrawn Phase 2 DMC FDA Drug

• 1 other identifier: Pro00109490
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if the study drug, patritumab deruxtecan (HER3-DXd), can be measured in brain tumor tissue after recieving one dose of patritumab deruxtecan before surgery.

Conditions

Brain Metastases, Adult

Keywords

Brain metastasis; Brain cancer; craniotomy; Patritumab Deruxtecan; Mustafa Khasraw; Pro00109490

Outcome Measures

Primary Outcomes (1)

• Determine the concentration of DXd in brain metastasis tumor tissue after one dose of the HER3-targeted ADC patritumab deruxtecan (HER3-DXd) administered via IV 1-3 days prior to craniotomy.

  The mean concentration of the DXd payload from patritumab deruxtecan will be computed. In addition, the distribution of the concentration will be examined

  3 days

Secondary Outcomes (3)

• Characterize the pharmacokinetics of ADC in serum, including ADC concentration and DXd concentration, collected at screening, pre-infusion, post-infusion, 4 hours post-infusion, 24 hours after patritumab deruxtecan administration, and at craniotomy.

  3 days

• Assess the evidence of tumor cell death via histopathological examination and measurement of γH2AX levels in tumor tissue.

  3 days

• Assess the safety of patritumab deruxtecan in patients with brain metastasis after the single dose and up to 40+7 days.

  40 days

Study Arms (1)

Patritumab deruxtecan

EXPERIMENTAL

15 participants with surgically-resectable brain metastases from multiple solid tumor primary histologies known to express HER3 will be treated. Patritumab deruxtecan (HER3-DXd) will be administered IV 5.6 mg/kg as a single dose 1-3 days prior to planned craniotomy and resection of BrM. Participants will undergo specimen collection prior to and during the planned craniotomy, including tumor, blood, and cerebrospinal fluid (CSF).

Drug: Patritumab deruxtecan

Interventions

Patritumab deruxtecan DRUG

Patritumab deruxtecan (HER3-DXd) will be administered IV 5.6 mg/kg as a single dose 1-3 days prior to planned craniotomy and resection of brain metastasis

Patritumab deruxtecan

Eligibility Criteria

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

You may qualify if:

• Participants must have newly diagnosed or recurrent brain metastases, with one of the metastases being surgically resectable. Primary tumor histology must be one of the following solid tumor types:
• Melanoma (cutaneous skin)
• Stomach adenocarcinoma (intestinal subtype)
• Breast invasive carcinoma
• ER+/PR+/HER2-
• HER2+ (any ER/PR status)
• Triple negative (ER-/PR-/HER2-)
• Colorectal adenocarcinoma
• Bladder Urothelial carcinoma
• Ovarian serous cystadenocarcinoma
• Serous subtype
• Mucinous subtype
• Cholangiocarcinoma
• Prostate adenocarcinoma
• Lung carcinoma

You may not qualify if:

• Female participants who are pregnant or breast-feeding or intend to become pregnant during the study.
• Participants with an impending, life-threatening cerebral herniation syndrome, based on the assessment of the study neurosurgeons or their designate.
• Participants with severe, active co-morbidity, defined as follow:
• Participants with an active infection requiring intravenous treatment or having an unexplained febrile illness (Tmax \> 99.5°F/37.5°C).
• Participants with known immunosuppressive disease or known human immunodeficiency virus (HIV) infection.
• Participants with unstable or severe intercurrent medical conditions such as severe heart disease (New York Heart Association Class 3 or 4).
• Participants with another malignancy within 1 year prior, except for adequately resected non-melanoma skin cancer, superficial bladder tumors (Ta, Tis, T1), adequately treated intraepithelial carcinoma of the cervix uteri, low risk non-metastatic prostate cancer (With Gleason score \<7 and following local treatment or ongoing active surveillance), curatively treated in-situ disease, or other solid tumors curatively treated.
• Participants with a known history of hypersensitivity to patritumab deruxtecan, or any components of patritumab deruxtecan.
• Participants who were previously treated with patritumab deruxtecan
• Participants with active autoimmune disease requiring systemic immunomodulatory treatment within the past 3 months.
• Participants with any history of interstitial lung disease (ILD) (including pulmonary fibrosis or radiation pneumonitis), has current ILD, or is suspected to have such disease by imaging during screening.
• 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. Full details of the disorder should be recorded in the eCRF for patients who are included in the study.
• Prior complete pneumonectomy
• Participant is receiving chronic systemic corticosteroids dosed at \>10 mg prednisone or equivalent anti-inflammatory activity or any form of immunosuppressive therapy prior to Cycle 1 Day 1. Participants who require use of bronchodilators, inhaled or topical steroids, or local steroid injections may be included in the study.

Sponsors & Collaborators

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP: lead
• Daiichi Sankyo: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Links

• The Preston Robert Tisch Brain Tumor Center at Duke
• Duke Health

MeSH Terms

Conditions

Brain Neoplasms

Interventions

patritumab deruxtecan

Condition Hierarchy (Ancestors)

Central Nervous System Neoplasms; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Study Officials

• Mustafa Khasraw, MBChB, MD, FRCP, FRACP

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Invesgitator

Study Record Dates

• First Submitted: November 10, 2022
• First Posted: November 17, 2022
• Study Start: July 1, 2025
• Primary Completion: April 1, 2026
• Study Completion (Estimated): April 1, 2027
• Last Updated: June 15, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)