Plus Therapeutics Announces Positive Interim Data in Clinical Trial for New Brain Cancer Treatment

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The following post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga.

Plus Therapeutics Inc. PSTV presented positive interim results from its ReSPECT-GBM Phase 1 clinical trial at the Society for Neuro-Oncology’s annual meeting in November.

The clinical-stage pharmaceutical company is focused on developing targeted radiotherapeutics to treat rare and difficult-to-treat cancers. Its leading drug candidate, Rhenium-186 NanoLiposome (186RNL), is being developed as a treatment for a rare but highly fatal form of brain cancer called recurrent glioblastoma (GBM). 

With no current standard of care and a survival rate of 12 to 15 months with treatment (and just 7-8 months without), GBM is an extremely aggressive brain cancer. With no current standard of care and a survival rate of 12 to 15 months with treatment (and just 7-8 months without), GBM is an extremely aggressive brain cancer in desperate need of better treatment options.

Plus Therapeutics hopes its radiation-based drug candidate 186RNL will become that better treatment option; recent promising data suggest that it has the potential to achieve that goal. 

How 186RNL Works

The targeted radiotherapeutic is administered using the latest convection-enhanced delivery (CED) technology. This delivery system helps the drug overcome one of the biggest obstacles to treating cancers located in the brain: the blood-brain barrier. 

When delivering drugs to other parts of the body, it’s possible to just inject it intravenously and know that a therapeutic dose will be absorbed. With the brain, the blood-brain barrier — which exists to block infections and toxins from entering the brain — prevents those drugs from reaching the brain. 

To bypass that, the CED technology that Plus Therapeutics is using involves placing a specialized catheter in the brain and then infusing nanoparticle-encapsulated radiation directly into the tumor.

The CED technique generates a pressure gradient at the catheter tip to safely and efficiently deliver therapeutics, such as 186RNL, directly through the interstitial spaces of the central nervous system.  The nanoparticle encapsulation delays the degradation process that would otherwise metabolize and remove the radiation before it has a chance to attack the tumor.

“This volume of distribution allows you to get a very high dose to the enhancing portion of the tumor,” said Dr. Toral Patel, the neurosurgeon and associate professor at UT Southwestern Medical Center (UTSW) working on the treatment explained during the presentation at the 2021 Society for Neuro-Oncology annual meeting. She added that this technology allowed researchers to deliver a “therapeutic dose to the at-risk zone.”

This improved ability to target the tumor more precisely not only bypasses that barrier but also improves both the efficacy and safety of the treatment. 

“It’s a very low dose rate that allows for increased safety for the normal tissues but a high radiation density, which should overwhelm the DNA repair mechanisms of the tumor cells,” said Dr. Andrew Brenner, associate professor of medicine, neurology and neurosurgery at the University of Texas and the principal investigator of the ReSPECT-GBM clinical trial of 186RNL.

Plus Therapeutics Releases Positive Interim Data for 186RNL

The ReSPECT-GBM Phase 1 trial has so far evaluated 22 adult patients with recurrent GBM over a 6-year period. Of these patients, 13 received higher doses of 186RNL above 100 Gray (Gy) — a unit of measurement used for measuring absorption of radiation — and the remaining nine patients received doses below 100 Gy.

All patients tolerated the treatment well with no patients stopping as a result of adverse events and no dose-limiting toxicities observed. Adverse effects were mild and non-life threatening; the side effects largely included headaches, fatigue and muscle aches.

The ReSPECT-GBM Phase 1 trial was only meant to evaluate tolerability and recommended dosing — not the efficacy of the drug — but the results the researchers are seeing are already encouraging. Higher doses were positively correlated with improved survival in the participants.

“The patients who have the greatest survival are the ones with the best coverage and best-absorbed doses,” Brenner said during Plus’s presentation. The neuro-oncologist added that results like this suggest that “if we can get better coverage, we can get better survival.”

While all nine patients receiving the lower dose died, seven of the 13 patients receiving the higher dose of 186RNL are still alive. In addition, the median survival rate across all 22 subjects was  231.5 days, the median survival rate for those receiving the higher doses was 330, or more than three additional months — a significant result for GBM patients, whose median survival is just eight months, according to Plus Therapeutics.

What Are the Next Steps for 186RNL?

With positive interim data, researchers are getting ready to move forward with further clinical studies on both dosing and efficacy with the hope of having strong data to bring to the Food and Drug Administration (FDA) by early next year. 

“In the first part of 2022, we’ll go to the FDA with the current data set to discuss the next clinical steps,” said Dr. Marc Hedrick, president and CEO of Plus Therapeutics.

The company is currently enrolling patients with recurrent glioblastoma for the next cohort of Phase 1. This cohort will receive a higher dose of 186RNL, approaching the recommended dose the researchers plan to use in Phase 2 trials.

“Our hope is to move this as carefully but as fast as we can to see if we can get this radiotherapeutic approved,” Hedrick said.

The preceding post was written and/or published as a collaboration between Benzinga’s in-house sponsored content team and a financial partner of Benzinga. Although the piece is not and should not be construed as editorial content, the sponsored content team works to ensure that any and all information contained within is true and accurate to the best of their knowledge and research. This content is for informational purposes only and not intended to be investing advice.