Plus Therapeutics Receives FDA Clearance for 186RNL Radiotherapy Trial in Leptomeningeal Metastases
核心洞察
Plus Therapeutics received FDA clearance for its Investigational New Drug application for 186RNL, a targeted radiotherapeutic for treating leptomeningeal metastases (搜索).
The ReSPECT-LM Phase 1 dose escalation trial will evaluate the safety and efficacy of 186RNL administered via intraventricular catheter in patients with this fatal cancer (搜索) complication.
Preclinical studies demonstrated tolerance to doses as high as 1,075 Gy with marked tumor burden reduction in animal models of leptomeningeal metastases (搜索).
Plus Therapeutics announced FDA clearance of its Investigational New Drug (IND) application for Rhenium-186 NanoLiposome (186RNL) for treating leptomeningeal metastases (搜索) (LM), a devastating cancer (搜索) complication with limited treatment options. The clinical-stage pharmaceutical company expects to initiate patient accrual for the Phase 1 dose escalation trial (ReSPECT-LM) in the fourth quarter of 2021.
Clinical Trial Design and Objectives
The ReSPECT-LM trial is designed as a multicenter, sequential cohort, open-label, single dose, dose escalation Phase 1 study. The trial will evaluate the maximum tolerated dose, maximum feasible dose, safety, and efficacy of a single administration of 186RNL via intraventricular catheter for patients with LM following standard surgical, radiation, and/or chemotherapy treatment.
The primary endpoint focuses on the incidence and severity of adverse events, serious adverse events, and dose limiting toxicities. Secondary endpoints include overall response rate, duration of response, progression free survival, and overall survival.
Preclinical Evidence Supporting Clinical Development
The Phase 1 clinical trial follows promising preclinical studies demonstrating tolerance to doses of 186RNL as high as 1,075 Gy in animal models with LM, with no observed significant toxicity. Treatment led to marked reduction in tumor burden in both C6 and MDA-231 LM models, providing strong rationale for clinical investigation.
"Given the excellent safety data thus far using 186RNL in recurrent glioblastoma (搜索), and the preclinical efficacy data when used in animal models of LM, we are optimistic about the potential safety and efficacy of 186RNL as a novel treatment option for LM," said Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas and ReSPECT-LM Principal Investigator.
Addressing Critical Unmet Medical Need
Leptomeningeal metastases (搜索) represents a rare but increasingly common secondary cancer (搜索) complication, occurring when cancer spreads to the membranes (meninges) surrounding the brain and spinal cord. The condition affects approximately 5% of people with cancer, translating to 110,000 people in the U.S. each year, and is usually terminal with a median survival of approximately 2-3 months following treatment.
"LM is an increasingly common secondary cancer (搜索) complication, occurring as a result of increasing observed survival rates for a variety of primary solid and hematologic tumors," Brenner explained. The most common cancers that metastasize to the leptomeninges include breast cancer (搜索), lung cancer (搜索), and melanomas.
Radiotherapeutic Platform Expansion
Marc H. Hedrick M.D., President and Chief Executive Officer of Plus Therapeutics, emphasized the strategic importance of this development: "Leptomeningeal metastasis is a neurologically devastating and fatal complication of cancer (搜索). Our latest approved IND application is part of a multifaceted plan to expand our radiotherapeutic pipeline with promising, innovative drugs to treat a variety of rare and difficult to treat cancers."
Plus Therapeutics' proprietary nanotechnology platform centers around enhanced drug delivery using novel liposomal encapsulation technology. The platform is designed to facilitate new delivery approaches and formulations of safe and effective injectable drugs, potentially enhancing safety, efficacy, and convenience for patients and healthcare providers.