Octs-07 Trial in Progress: Phase Ii Study of Radiation Therapy Followed by Intrathecal Trastuzumab/Pertuzumab in the Management of Her2+ Breast Leptomeningeal Disease

BACKGROUND HER2+ leptomeningeal disease (LMD) has a poor prognosis with a high unmet clinical need. A previous phase I/II study revealed intrathecal (IT) trastuzumab to be well tolerated with improved overall survival (OS) compared to historical controls in HER2+ breast LMD. Radiotherapy can improve the flow of IT therapy through the cerebrospinal fluid (CSF) and provide symptomatic relief. The monoclonal antibody pertuzumab is used in conjunction with trastuzumab in the systemic management of HER2+ breast cancer. The phase I portion of the current study used a modified toxicity probability interval-2 (mTPI-2) design to determine 80 mg IT pertuzumab as the recommended phase II dose with a fixed dose of 80 mg IT trastuzumab. METHODS The study is designed as a prospective, single-arm, nonrandomized, open-label, phase II trial of radiation therapy followed by IT trastuzumab/pertuzumab in the management of HER2+ breast LMD. HER2+ LMD patients identified by magnetic resonance imaging (MRI) and/or CSF cytology, ≥18, with a life expectancy > 8 weeks are eligible. Treatment is initiated with radiotherapy, whole brain radiotherapy and/or focal brain/spine radiation followed by IT trastuzumab/pertuzumab. The primary objective of the phase II portion is to evaluate OS following IT trastuzumab/pertuzumab. Secondary objectives involve evaluating the response rate (leptomeningeal and parenchymal), and progression free survival (leptomeningeal and parenchymal). A single-arm two-stage trial is designed using the Restricted-Kwak-and-Jung’s Method. The primary endpoint is one-year OS. An interim analysis will be performed after 20 patients are enrolled with plans to enroll an additional 10 patients if criteria are met. This study is open with 14 patients enrolled at the time of submission. Clinical trial information: NCT04588545.