HER3-DXd in Breast Cancer and NSCLC Brain Metastases and Solid Tumor Leptomeningeal Disease (NCT05865990) | Clinical Trial Compass
CompletedPhase 2
HER3-DXd in Breast Cancer and NSCLC Brain Metastases and Solid Tumor Leptomeningeal Disease
Austria, Spain63 participantsStarted 2023-11-24
Plain-language summary
The goal of this phase II clinical trial\] is to analyze the efficacy of patritumab deruxtecan (HER3-DXd) in patients with metastatic breast cancer (MBC) or advanced non-small cell lung cancer (aNSCLC) with active brain metastases (BM) who have received at least one line of systemic therapy in the advanced setting, or patients with active leptomeningeal carcinomatosis/disease (LMD) after radiotherapy from an advanced solid tumor who do not need immediate local treatment, and have not received prior treatment with an anti-HER3 targeted drug\].
The main questions it aims to answer are:
* The intracranial objective response rate (ORR-IC) per local investigator as judged by best central nervous system (CNS) response according to Response Assessment in Neuro-Oncology Brain Metastases (RANO-BM) criteria of HER3-DXd in patients with active BM from MBC (Cohort 1) and aNSCLC (Cohort 2).
* The overall survival (OS) rate at 3 months of HER3-DXd in patients with advanced solid tumors with untreated LMD (Cohort 3).
Participants will receive HER3-DXd on day (D1) of each 21-day cycle until disease progression, unacceptable toxicity, death, or discontinuation from the study treatment for any other reason.
Researchers will compare historical groups to see if HER3-DXd positively impacts patient outcomes.
Who can participate
Age range
18 Years
Sex
ALL
See this in plain English?
AI-rewrites the medical criteria so a patient or caregiver can understand them. Always confirm with the trial site.
Inclusion criteria
. Patient must be capable to understand the purpose of the study and have signed written informed consent form (ICF) prior to beginning specific protocol procedures.
. Age ≥ 18 years at the time of signing ICF.
. Life expectancy ≥ 6 weeks.
. Karnofsky Performance Status (KPS) ≥70%, Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≤ 2.
. Patient must be able to tolerate therapy.
. Availability and willingness to provide the most recently available tumor tissue sample (formalin-fixed and paraffin-embedded \[FFPE\], no cytology/cell block, no bone/decalcified bone sample) of primary tumor or any metastatic site from biopsy collected after last round of prior treatment and ≤ 6 months prior to HER3-DXd, if possible, at the time of inclusion for retrospective exploratory biomarker testing. If archival tissue is not available, a newly obtained baseline biopsy of an accessible tumor lesion is required prior to start of study treatment (unless not possible because of inaccessible tumor location or safety concerns). Collection and/or shipment of pre-treatment tumor tissue biopsy for retrospective biomarker testing should be at least initiated treatment at the time of inclusion.
Questions worth asking your doctor
Bring these to your next appointment. They're a starting point for a shared conversation — not a sign you qualify or a recommendation to enrol.
1Based on my diagnosis and history, is this trial worth exploring for me — or is there a standard treatment we should try first?
2What does this trial's phase tell us about how much is already known about its safety and benefit?
3What would taking part actually involve for me — visits, tests, time, and travel?
4What are the known and possible risks or side effects I should weigh, and how would they be monitored?
5If this trial isn't the right fit, what other options or trials would you suggest I look into?
Generated to help you prepare — always confirm anything about your own eligibility and care with the study team and your doctor.
Questions for the trial coordinator
The trial coordinator is the person who runs the study day to day. These cover the practical side — logistics, costs, and what taking part would actually mean for your life. The study team confirms whether you meet the criteria; these are questions to ask, not a sign you qualify.
1What does taking part actually involve week to week — how many visits, where, and how long does each one take?
2What costs are covered by the study, and what might I have to pay for myself, including travel, parking, or time off work?
3What happens during screening, and what happens if the study team confirms I don't meet the criteria after those tests?
4Who pays for the scans, blood work, and other tests the trial requires — the study, my insurance, or me?
5How will being in the trial affect my regular care, and will my own doctor stay informed and involved?
6Can I leave the trial at any point if I change my mind, and what would happen to my care if I do?
A starting point for the conversation — always confirm anything about your own eligibility, costs, and care with the study team and your doctor.
What they're measuring
1
Efficacy: Local determination of intracranial objective response rate (ORR-IC) in cohort 1 and cohort 2.
Timeframe: From baseline to the date of first documented progression, death from any cause, or treatment discontinuation from any reason, whichever came first, assessed up to 12 months
2
Efficacy: Overall survival (OS) rate at 3 months in cohort 3.
. No indication for immediate local therapy (neurosurgery, brain radiotherapy).
. Patient has adequate bone marrow, liver, and renal function:
Exclusion criteria
. Current participation in another therapeutic clinical trial.
. Treatment with approved or investigational cancer therapy within 14 days prior to initiation of study drug.
. Patients have a concurrent malignancy or malignancy within five years of study enrollment with the exception of carcinoma in situ of the cervix, non-melanoma skin carcinoma, or stage I uterine cancer. For other cancers considered to have a low risk of recurrence, discussion with the Medical Monitor is required.
. Previous systemic therapy with any anti-HER3 directed drug.
. Known allergy or hypersensitivity to HER3-DXd or any of the drug components.
. Radiotherapy or limited-field palliative radiotherapy within seven days prior to study enrolment, or patients who have not recovered from radiotherapy-related toxicities to baseline or grade ≤ 1 and/or from whom ≥ 25% of the bone marrow has been previously irradiated.
. Patients with an active cardiac disease or a history of cardiac dysfunction or conduction abnormalities including any of the following:
. Unstable angina pectoris or documented myocardial infarction within 6 months prior to study entry.