Blue Earth Therapeutics’s injectable investigational radioligand therapy, Lutetium rhPSMA-10.1, has led to higher doses of radiation in tumours than healthy tissue in patients with prostate cancer.
Findings from the Phase I portion of the Phase I/II open-label, integrated trial (NCT05413850) saw Lutetium rhPSMA-10.1 able to sustain a mean biological half-life of 338 hours in tumour tissue, giving the treatment an effective mean half-life of 91.4 hours when paired with the 6.7-day physical half-life of Lutetium. At the same time, results showed a mean tumour-to-salivary gland absorption ratio of 73 and a tumour-to-kidney absorption ratio of 32.
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The median absorbed radiation dose to tumours, defined by single photon emission computed tomography (SPECT) imaging, was 8.9 Gy for each GBq of radioactivity. The mean absorbed radiation dose to the kidneys was 0.27 Gy/GBq; to salivary glands, 0.13Gy/GBq.
Prostate-specific membrane antigen (PSMA) is a protein typically overexpressed on the surface of cancer cells, making it an ideal target for targeted radiotherapy treatments.
As a result, the company states that Lutetium rhPSMA-10.1 can surpass currently available radioligand therapies in the field by one and a half to twice the length of time.
Now, the Oxford-based company has announced plans to move ahead to the Phase II portion of the trial amid discussion with regulatory authorities that are set to explore the use of significantly higher overall injected radioactivity in comparison to other recent Phase III clinical trials of other PSMA-targeted radioligand therapies.
Dr. David Gauden, CEO of Blue Earth Therapeutics, said, “The Phase I data provides strong validation of the innovative approach taken on optimising radioligand therapy by Blue Earth Therapeutics and the inventors of the rhPSMA technology.”
“The relative ratios of the tumour to healthy organ absorbed radiation doses are key metrics in establishing a better profile of the risks and potential benefits of radioligand therapies. With radioligand therapies, normal organ toxicity considerations gate the total amount of radioactivity that can be administered, so the more of the radioactivity that accumulates in tumours, the better,” Gauden added.
The Phase I trial recruited 13 metastatic castrate-resistant prostate cancer patients from five sites across the US and Netherlands. The Phase I study’s primary endpoint sought to establish the rate of dose-limiting toxicities as well as treatment-emergent adverse events. The Phase II trial will examine the number of patients with an anti-tumour response at 12-week intervals.
Gauden added: “Our goal is to substantially increase the potential for prostate cancer patients to benefit compared to available radioligand therapy, and completion of this study moves us closer to making that goal a reality.”
The announcement follows the company’s clinical research partnership with University College London (UCL) in the UK to progress the clinical development of its therapies. Elsewhere in the field of radioligand therapy, Repare Therapeutics has dosed the first patient in its Phase I POLAR clinical trial of RP-3467, a Polθ ATPase inhibitor, as a potential treatment for various solid tumours.
