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 range18 Years
SexALL
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.
✓. No indication for immediate local therapy (neurosurgery, brain radiotherapy).
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.
. 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.