On September 12, 2022 Plus Therapeutics, Inc. (Nasdaq: PSTV) (the "Company"), a clinical-stage pharmaceutical company developing innovative, targeted radiotherapeutics for rare and difficult-to-treat cancers, reported Phase 1 data from the ReSPECT-GBM Phase 1/2a dose escalation clinical trial evaluating the Company’s lead investigational targeted radiotherapeutic, Rhenium-186 NanoLiposome (186RNL), in recurrent glioblastoma (GBM) in an oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022, being held September 9-13, 2022 in Paris, France (Press release, PLUS THERAPEUTICS, SEP 12, 2022, View Source;_hsmi=225740869&_hsenc=p2ANqtz–6YFoZ8ZUpThJHOJugmdD8dgg2haHyg6iYf86gY_0MCeKN2rY0_GGFEXgLIEtD4CesBA5r_5RUW2PTlyFZ_lP6B5F-qQ&utm_content=225740869&utm_source=hs_email [SID1234619446]).

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"Radiation is lethal to cancer cells and rhenium-186 is an ideal radioisotope for the treatment of glioblastoma. Furthermore, the unique drug formulation allows the radiation to stay in the brain for days, if not weeks," said Andrew J. Brenner, M.D., Ph.D., Professor of Medicine, Neurology, and Neurosurgery at The University of Texas Health Science Center at San Antonio and principal investigator of the ReSPECT-GBM clinical trial. "In the ReSPECT-GBM Phase 1 trial, we achieved up to 20 times the amount of radiation compared to external beam radiation therapy, and we observed a statistically significant improvement in survival in those patients receiving a therapeutic dose of radiation compared to those that did not."

The oral presentation titled, The ReSPECT-GBM Phase 1/2a Dose Escalation Trial of Rhenium-186 NanoLiposome (186RNL) in Recurrent Glioma via Convection Enhanced Delivery (CED) & Planned Phase 2b Trial [2770], reviews data from the Phase 1 ReSPECT-GBM trial which evaluated 23 adult patients with recurrent GBM across 8 cohorts of increasing dose and treated over a seven-year period.

Key findings include:

No dose-limiting toxicities (DLT) have been observed and the procedure is very well tolerated with a strong safety profile. Minimal systemic radiation has been observed and the majority of adverse events have been mild or moderate and considered causally unrelated to the procedure.
Improved median overall survival (OS) rates correlated with the absorbed tumor radiation dose. When patients were stratified based on receipt of either a therapeutic or a subtherapeutic absorbed dose of radiation to the tumor, a statistically significant improvement in survival was observed. Specifically, patients receiving a therapeutic absorbed radiation dose (>100 Gray) had a median OS of 22.9 (95% CI of 8.8-42.3) months compared to those receiving a subtherapeutic absorbed radiation dose (<100 Gray) whose median OS was 5.6 months (95% CI of 1.6-9.4). Currently, three patients remain alive, all in the therapeutic group.
Feasibility to deliver up to at least 20 times more radiation to the tumor than the standard of care, external beam radiation therapy (EBRT). A maximum of 32.2 mCi in 12.3 mL of volume has been delivered in and near the tumors, and a maximum average absorbed dose of radiation of 740 Gray has been successfully administered in a single procedure.
Average absorbed radiation dose to the tumor increased in latter dosing cohorts with greater administered doses of Re-186 β-particle radiation, larger drug convection enhanced delivery (CED) infusate volumes, more catheters used (up to 4 versus 1), and higher convection flow rates. In cohorts 5 and later, 82% of patients received a therapeutic radiation dose of >100Gray.
Single-photon emission computerized tomography and (SPECT)/CT scanning were used during treatment to compute tumor coverage and dosimetry. Post treatment imaging analyses, including MRI, relative cerebral blood volume (rCBV) analysis and treatment response assessment maps (TRAMs) correlated with a positive tumor response and confirmed the presence of pseudoprogression in patients with positive tumor responses.
ReSPECT-GBM will proceed to an NIH and U.S. Food and Drug Administration (FDA) approved Phase 2 trial in the U.S. at the current non-DLT 186RNL dose and will expand exploring higher radiation doses in larger volumes to treat larger tumors. Additionally, two or more 186RNL administrations, if indicated, will be evaluated and reviewed with the FDA, as well as expanded safety, imaging and efficacy data to support a planned future registrational trial.
"The Phase 1 data offer important and objective insight and data into 186RNL’s potential to safely prolong patient survival and suggests that there is an overall survival benefit when a 186RNL dose of more than 100 Gray is achieved," said Norman LaFrance, M.D., Chief Medical Officer and Senior Vice President at Plus Therapeutics. "The planned Phase 2 study using cGMP 186RNL will leverage a higher dose and volume that could potentially show a greater survival rate in patients with recurrent GBM."

Based upon feedback from a Type C meeting with the FDA, the Company plans to initiate the ReSPECT-GBM Phase 2 trial in the second half of 2022, funded principally by the NIH. The Company intends to begin the ReSPECT-GBM Phase 2 trial utilizing cGMP 186RNL drug, which will be available in the second half of 2022. In this study, researchers plan to administer the recommended non-DLT dose of 22.3 mCi (total 186RNL activity) at a concentration of 2.5 mCi/mL in 8.8 mL total volume to patients with a tumor size of less than or equal to 20 cm3 as a starting point. Furthermore, the Company plans to evaluate further doses, including both increased dosing and multiple doses, and collect additional safety and efficacy data for the planned future registrational trial.

A copy of the presentation will be available under the Presentations tab of the Investors section of the Company’s website at the time of presentation at View Source