Core Insights - Plus Therapeutics, Inc. has completed a Type B meeting with the FDA regarding the pivotal trial strategy for REYOBIQ in treating leptomeningeal metastases (LM), leading to constructive discussions on study design [1][3] - The company aims to incorporate FDA feedback into its current dose optimization trial and plans to align on a revised protocol later this year, with the goal of preparing for a pivotal trial [1][3] - REYOBIQ is a novel injectable radiotherapy designed for CNS tumors, with potential advantages over existing therapies, and is currently being evaluated in multiple clinical trials [5][8] FDA Meeting Highlights - The FDA indicated that accelerated approval may be appropriate for the LM indication, but more data is needed to validate circulating tumor cells (CTCs) as a surrogate endpoint [6] - The FDA recommended evaluating endpoints with established clinical benefits, such as overall survival, while considering CTCs as a secondary endpoint [6] - A randomized controlled trial design was discussed, potentially including an intrathecal chemotherapeutic as a comparator [6] About Leptomeningeal Metastases - LM is a rare but severe complication of advanced cancer, occurring in approximately 5% of metastatic cancer patients, with a median survival of 2-6 months [4] - Common sources of LM include breast cancer, lung cancer, and melanoma, highlighting the urgent need for novel therapies [4] About REYOBIQ - REYOBIQ (rhenium Re186 obisbemeda) is formulated to deliver targeted high-dose radiation in CNS tumors, aiming to optimize patient outcomes with reduced off-target risks [5] - The product is being evaluated for recurrent glioblastoma, LM, and pediatric brain cancer in various clinical trials, supported by significant grants from the National Cancer Institute and other organizations [5] Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for challenging CNS cancers, with a pipeline that includes treatments for LM and recurrent glioblastoma [8] - The company has established a supply chain through strategic partnerships to support the development and future commercialization of its products [8]

Core Insights - Plus Therapeutics, Inc. presented positive clinical data for REYOBIQ at the WFNOS/SNO Annual Meeting, indicating no dosage limiting toxicity in the ReSPECT-LM trial and promising safety and efficacy in the ReSPECT-GBM trial [1][2][12] - The company aims to improve survival rates for patients with central nervous system (CNS) cancers through its expanding clinical data set and the CNSide diagnostic portfolio [2][12] ReSPECT-LM Trial - The Phase 1 trial for Leptomeningeal Metastases (LM) showed that REYOBIQ was well-tolerated at a maximum dose of 66 mCi, with a recommended Phase 2 dose of 44.1 mCi [7] - Enrollment in Cohort 1 has begun, with three patients treated without dose limiting toxicity [7] ReSPECT-GBM Trial - The Phase 1/2 trial for recurrent Glioblastoma (GBM) has enrolled 24 out of a planned 34 patients, with a recommended Phase 2 dose of 22.3 mCi based on safety profiles [8] - Efficacy data indicated a median overall survival of 17 months for patients receiving ≥100 Gy, compared to 6 months for those receiving <100 Gy, surpassing historical outcomes for bevacizumab monotherapy [14] Safety Profile - Most treatment-related adverse events in both Phase 1 and 2 trials were Grade 1 or 2, with no treatment-related deaths reported [9] - Common adverse events included lymphopenia (7.9%), cognitive disorder (7.0%), and headache (7.0%) [9] Imaging and Efficacy - MRI combined with SPECT imaging biomarkers effectively evaluates overall survival response in recurrent GBM treatment, aiding in personalized patient planning [12][14] - REYOBIQ's efficacy is positively correlated with treatment coverage ratio and progression-free survival, while negatively correlated with tumor volume [14] About REYOBIQ - REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy designed for targeted high-dose radiation in CNS tumors, with potential advantages over currently approved therapies [15] - The drug is being evaluated in multiple clinical trials, including ReSPECT-GBM, ReSPECT-LM, and ReSPECT-PBC, with funding support from various institutions [15]

Core Insights - Plus Therapeutics, Inc. is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for central nervous system (CNS) cancers, with an abstract accepted for a poster spotlight presentation at the San Antonio Breast Cancer Symposium [1][2] Group 1: Company Overview - Plus Therapeutics is headquartered in Houston, Texas, and specializes in targeted radiotherapeutics aimed at difficult-to-treat CNS cancers, aiming to enhance clinical outcomes [6][7] - The company is advancing a pipeline of product candidates, particularly in leptomeningeal metastases (LM) and recurrent glioblastoma (GBM) [7] Group 2: Product Information - REYOBIQ (rhenium Re186 obisbemeda) is a novel injectable radiotherapy designed to deliver targeted high-dose radiation to CNS tumors, potentially improving patient outcomes compared to existing therapies [4] - REYOBIQ is currently being evaluated in clinical trials for recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer, with significant funding support from various institutions [4] Group 3: Clinical Context - Leptomeningeal metastases (LM) occur in approximately 5% of patients with metastatic cancer, with a median survival of 2-6 months, indicating a critical need for effective treatment options [3] - The CNSide Diagnostics, LLC, a subsidiary of Plus Therapeutics, develops tests to identify tumor cells that have metastasized to the CNS, enhancing patient management for those with LM [5]

Core Insights - Plus Therapeutics has completed a Type B meeting with the FDA to discuss clinical development plans for REYOBIQ targeting leptomeningeal metastases [1][2] - The company plans to provide an update on next steps early in 2026 and will implement amendments to the LM trial based on FDA recommendations [2] About Leptomeningeal Metastases (LM) - LM is a severe complication of advanced cancer, occurring in approximately 5% of metastatic cancer patients, with a median survival of 2-6 months [3] - Common sources of LM include breast cancer, lung cancer, and melanoma, highlighting the urgent need for novel therapies [3] About REYOBIQ™ - REYOBIQ is a novel injectable radiotherapy designed for targeted high-dose radiation in CNS tumors, potentially improving patient outcomes compared to existing therapies [4] - It is being evaluated in clinical trials for recurrent glioblastoma, leptomeningeal metastases, and pediatric brain cancer, with significant funding support from various institutions [4] About CNSide Diagnostic, LLC - CNSide Diagnostics, a subsidiary of Plus Therapeutics, develops proprietary tests to identify tumor cells in the CNS, aiding in the management of patients with leptomeningeal metastases [5] About Plus Therapeutics - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for CNS cancers, with a pipeline that includes programs for LM and recurrent glioblastoma [6] - The company has established a supply chain through strategic partnerships to support the development and potential commercialization of its products [6]

Core Insights - Plus Therapeutics, Inc. announced positive data from the ReSPECT-LM Phase 1 trial, demonstrating a clinical benefit rate of over 75% in three relevant outcome measures for the treatment of leptomeningeal metastases with REYOBIQ [1][2] - The trial showed no dose-limiting toxicities and an overall favorable safety profile, indicating the treatment is feasible and effective [1][4] Study Details - The Phase 1 trial involved 29 subjects across six cohorts receiving varying doses of REYOBIQ, ranging from 6.6 mCi to 75 mCi [2] - Early cohorts exhibited excellent tolerance at higher doses, supporting a broad therapeutic range [4] Efficacy and Safety - The study reported a radiographic response rate of 76% and a clinical response rate of 87% through day 112 [6] - CSF tumor cell enumeration assays showed a maximum reduction of 100% at day 28, with a median overall survival of 9 months across the first four cohorts, which is significantly better than the typical 2-6 months reported in literature [6] Future Directions - The trial results provide a foundation for moving into ongoing dosing optimization and potential approval trials [4] - REYOBIQ is being evaluated for multiple CNS cancers, including recurrent glioblastoma and pediatric brain cancer, with significant funding support from the National Cancer Institute and the Cancer Prevention & Research Institute of Texas [5][7]

Core Viewpoint - Plus Therapeutics has initiated the ReSPECT-LM dose optimization trial for REYOBIQ™ to determine the optimal dosing schedule for treating leptomeningeal metastases, building on previous trial results and supported by a $17.6 million grant from CPRIT [1][7]. Trial Design and Objectives - The trial aims to optimize treatment dosing for maximum efficacy and safety, focusing on the safety and tolerability of multiple REYOBIQ doses administered via intraventricular catheter [2]. - Primary objectives include identifying the maximum tolerated dose and minimum effective dose for patients with LM from any primary solid tumor cancer [2]. Enrollment and Study Details - The trial will enroll up to 24 patients, evaluating REYOBIQ at a recommended Phase 2 dose of 44.1 mCi across three dosing intervals [4]. - Key cohorts include dosing intervals of 56 days, 28 days, and 14 days, with up to six patients per cohort [4]. Efficacy and Safety Data - Previous trials showed a clinical benefit rate of 76%, with 29% of patients achieving partial responses and 47% maintaining stable disease [5]. - No dose-limiting toxicities were observed in the first four cohorts, although one Grade 4 DLT occurred in each of Cohorts 5 and 6 [5]. Future Plans - The company plans to present data from the completed single-dose escalation trial at the SNO/ASCO CNS Metastases Conference in August 2025 and will request an End of Phase 1 Type B meeting with the FDA [6]. About Leptomeningeal Metastases - Leptomeningeal metastases occur in approximately 5% of patients with metastatic cancer, with median survival typically ranging from 2 to 6 months, highlighting the urgent need for effective treatment options [8]. About REYOBIQ™ - REYOBIQ™ is a novel injectable radiotherapy designed for targeted high-dose radiation in CNS tumors, with potential advantages over currently approved therapies [9]. Company Overview - Plus Therapeutics is a clinical-stage pharmaceutical company focused on developing targeted radiotherapeutics for challenging CNS cancers, with a pipeline that includes treatments for leptomeningeal metastases, recurrent glioblastoma, and pediatric brain cancer [10].