Clinical Research Directory

Emulation of the CheckMate 017/057 (NCT01642004 and NCT01673867) Trials Using Specialty Oncology Electronic Health Records Databases

Investigators are building an empirical evidence base for real world data through large-scale emulation of randomized controlled trials. The investigators' goal is to understand for what types of clinical questions real world data analyses can be conducted with confidence and how to implement such studies.

HER3-DXd in Breast Cancer and NSCLC Brain Metastases and Solid Tumor Leptomeningeal Disease

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.

Phase 1/2 Study of Silevertinib (BDTX-1535) in Patients With Glioblastoma or Non-Small Cell Lung Cancer With EGFR Mutations

BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of silevertinib (BDTX-1535). The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma (GBM) expressing EGFR alterations (Phase 1 only). All patients will self-administer silevertinib (BDTX-1535) monotherapy by mouth in 21-day cycles. Phase 1 enrollment is now complete. Phase 2 is currently ongoing.

Whole Body HER3 Quantification With Radiolabelled Patritumab Deruxtecan (HER3-DXd) PET/CT

Activity of patritumab deruxtecan (U3-1402; HER3-DXd) has been shown in a phase I/II study in patients with HER3 expressing breast cancer as well as in a phase I study in patients with EGFR TKI refractory EGFR mutation positive NSCLC with a preliminary ORR of 25%. HER3 expression can be seen in multiple tumor types and is therefore an attractive target for antibody drug conjugate (ADC) treatment. However, intra- and intertumor heterogeneity of HER3 expression might be substantial, as is seen for HER2, and might contribute to treatment failure or heterogeneous responses. In addition, HER3 expression is dynamic and has been shown to change over time. In order to identify patients that may benefit most from treatment with patritumab deruxtecan, better knowledge of the in vivo behaviour of the drug is warranted. One way to visualize this behaviour is positron emission tomography (PET) imaging with radiolabelled antibodies (immune-PET). 89Zr-Patritumab deruxtecan PET/CT can assess HER3 expression non-invasively at a whole body level, including sites that may be difficult to biopsy. It also visualizes and quantifies biodistribution of patritumab deruxtecan, thereby obtaining valuable information for safety and toxicity analyses.

Primary Tumor Radiotherapy Omitting CTV for Patients With Advanced NSCLC Responded to Immunotherapy and Chemotherapy

The aim of this randomized study is to investigate pneumonitis, local tumor control, and survival outcomes of primary tumor radiotherapy omitting CTV for patients with advanced NSCLC responded to immunotherapy and chemotherapy