First-in-Human – Therapy for Leptomeningeal Metastases.

ReSPECT-LM trial to evaluate safety/tolerability and identify MTD/MFD in three cohorts.
therapy

Therapy for Leptomeningeal Metastases.

Plus Therapeutics, a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, today announced that the first patient has been dosed in the ReSPECT-LM Phase 1/2a dose escalation clinical trial of Rhenium-186 NanoLiposome for the treatment of patients with leptomeningeal metastases (LM).

The investigational drug, 186RNL, is a proprietary nanoscale compound with a unique chelated radioisotope that is administered locally as a single dose via a conventional Ommaya reservoir. Rhenium-186 is a dual energy emitter (beta and gamma) with a short average path length for high precision, low dose rate that is safer for normal tissues, and high radiation density that overwhelms innate DNA repair mechanisms. The dual energy emission allows real time evaluation and monitoring of the 186RNL administration.

The disease target, solid tumor-originating LM, is a deadly and increasingly common central nervous system (CNS) complication potentially from all solid cancer, with breast cancer, lung cancer, gastrointestinal cancer and melanoma being the most common primary sources of LM, with 110,000 cases diagnosed annually in the U.S. LM affects the membranes (meninges) surrounding the brain and spinal cord. There are currently no meaningfully effective Food and Drug Administration-approved treatments.

“The rationale for use of 186RNL in LM patients is scientifically quite attractive, and in clinical practice was very straightforward to administer to our first patient,” said Michael Youssef, M.D., Assistant Professor of Neuro-Oncology at University of Texas Southwestern and site Principal Investigator. “Quality of life and survival rates are poor among patients diagnosed with LM from solid tumors. With no standard of care, this represents a true unmet medical need in neuro-oncology.”

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“LM affects about 10 times the number of patients as glioblastoma but carries a substantially worse prognosis,” said Norman LaFrance, M.D., Chief Medical Officer and SVP of Plus Therapeutics. “Initiating treatment in LM patients with 186RNL marks an important milestone for Plus Therapeutics and potential for the LM patient population.”

The ReSPECT-LM trial is a multicenter, sequential cohort, open-label, single dose, dose escalation Phase 1/2a study using a modified Fibonacci 3+3 study design. It will evaluate the maximum tolerated dose (MTD), maximum feasible dose (MFD), safety and efficacy of a single administration of 186RNL via intraventricular catheter for LM following standard surgical, radiation and/or chemotherapy treatment.

The primary endpoints of the study are 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.

The ReSPECT-LM Phase 1/2a clinical trial follows preclinical studies in which tolerance to doses of 186RNL as high as 1,075 Gy was shown in animal models with LM with no observed significant toxicity. Treatment led to a marked reduction in tumor burden in two animal models of LM.

The Company recently announced the FDA granted Fast Track designation to 186RNL for the treatment of LM. Fast Track designation confers several benefits to the drug development program, including 1) more frequent meetings with and written communication from FDA, 2) eligibility for Accelerated Approval and Priority Review, if relevant criteria are met, and 3) Rolling Review, which allows a drug company to submit completed sections of its New Drug Application (NDA) for review by FDA, rather than wait until every section of the NDA is completed before the entire application can be reviewed.

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