At the 2024 SIR Annual Meeting, Robert Abraham, MD, FSIR, FRCPC, Dalhousie University, Halifax, Nova Scotia, Canada, presented safety and efficacy results from a trial evaluating the use of multimodal imageable glass Y90 microspheres (Eye90 microspheres) for radioembolization for patients with hepatocellular carcinoma.

This interim report of the first-in-human trial demonstrated that imageable glass Y90 microspheres are safe and effective at 6 months after selective radioembolization among patients with hepatocellular carcinoma.

Transcript:

Robert Abraham, MD, FSIR, FRCPC: I am Bob Abraham, an Interventional Radiologist at the QEII Health Sciences Center in Halifax, Nova Scotia and Professor of Radiology at Dalhousie University. I am also co-founder of ABK Biomedical, a medical device company developing imageable glass microspheres including the investigational device being discussed here.

IO Learning: What are the imageable glass Y90 (Eye90) microspheres? How do they differ from other Y-90 microspheres (TheraSphere, SIR-sphere) on the market?

Dr Abraham: Eye90 microspheres® are glass Y-90 microspheres similar to TheraSphere in size and therapeutic beta emission but with radiopaque elements integrated into the composition to allow for direct visualization of Eye90 microsphere distribution in tumor using CT-based imaging modalities. In addition, Eye90 is delivered through a proprietary advanced administration system that allows for controlled and consistent microsphere injection with the ability to stop injection, potentially assess progress by evaluating microsphere coverage of tumor through CT, or assess catheter position and blood flow by injecting contrast prior to resuming injection as needed.

IO Learning: What are some practical or clinical points that clinicians should know about these microspheres?

Dr Abraham: The ability to directly visualize Eye90 microsphere distribution on readily available CT imaging modalities could allow for early recognition of inadequate targeting and coverage of tumor allowing for actionable management decisions such as seeking additional arterial supply to tumor that had been inadequately targeted and could then be treated. Potentially, this could be done in real-time during treatment through the use of hybrid CT/angio units or possibly by cone beam CT integrated with current interventional imaging systems.

IO Learning: What is the background/rationale and methods for this first-in-human trial, presented at SIR?

Dr Abraham: This is a prospective, single center, first-in-human pilot study to evaluate safety and efficacy of Eye90 that will inform a larger multicenter trial. This study is being conducted in Auckland, New Zealand and the primary investigator is Professor Andrew Holden. Child Pugh A subjects were enrolled with ECOG 0 or 1 performance status, liver only unresectable Hepatocellular Carcinoma, 1 lesion at least 2 cm in diameter with a maximum of 3 lesions with a total linear lesion length of 9 cm or less.  After obtaining baseline clinical and biochemical parameters and multiphase CT and MRI, subjects underwent standard Y-90 angiographic workup and 99TcMAA SPECT/CT to obtain lung shunt and tumor to normal ratio parameters. Subjects were then treated with selective therapy with Eye90 using partition dosimetry targeting a minimum tumor absorbed dose of 205 Gy. Post Eye90 SPECT/ CT was obtained to evaluate Eye90 radioactivity distribution and to determine absorbed dose quantification and a 4-phase Liver CT scan was also included to evaluate Eye90 radiopacity distribution.

For safety assessment, we are conducting in-clinic visits and blood chemistry at set intervals to evaluate adverse events, treatment related serious adverse events and CTCAE Grade 3 or greater toxicity. For efficacy, we are evaluating overall response rate by localized mRECIST on multiphase MRI every 3 months. Subjects are to be followed out to 12 months.

IO Learning: What were the results presented?

Dr Abraham: At SIR, we reported on the preliminary 6-month safety and efficacy results. Six patients have been enrolled and treated prior to study close. Mean tumor diameter was 3.0 cm. Eye90 mean activity administered was 1.5 GBq with a mean quantity of 182 mg which equates to approximately 5.2 million microspheres. All treatments were well tolerated. All patients had adverse events expected with radioembolization, such as pain and fatigue, but there were no treatment-related serious adverse events and no evidence of radioembolization-induced liver disease or lung injury. Three of the 6 subjects (50%) had complete response at 3 and 6 months and 1 subject had partial response by localized mRECIST at these time points. Additionally, 1 subject had partial response and another had stable disease at 3 months. Both these patients underwent chemoembolization to treat residual disease and could not be evaluated at 6 months.

Below are representative images from a subject in this study showing complete response by mRECIST:

IO Learning: How are these results significant and what are the next steps for this research?

Dr Abraham: Though these are preliminary results in a limited study with a small number of patients, the results demonstrate that subjects can be treated successfully and safely with Eye90. The study results have provided information that informs a larger prospective, open-label, multicenter US IDE pivotal trial that has since commenced named Route90. Route90 is being conducted to evaluate safety and efficacy for Eye90 microspheres in up to 120 patients. In that study, we will be exploring potential additional benefits of Eye90 such as the ability to confirm adequate tumor targeting/coverage using CT modalities and the potential to use calibration phantoms to quantify Eye90 radiopacity in treated regions and convert this to CT radiopacity-based tumor absorbed dose, a process that we call CT Dosimetry.

Below, is a case example to illustrate this concept:

IO Learning: Is there anything else regarding this trial that you would like to add?

Dr Abraham: We will follow our patients in this pilot trial out to 12 months to assess whether the preliminary results are maintained, and we look forward to confirming the findings in the pilot study in the US Route90 trial where we hope to further illustrate the advantages of this investigational product that has recently received FDA Breakthrough designation.

Source:

Abraham R, Verma Amit, Dobrowski D, et al. Multimodal Imageable Eye90 microspheres® Radioembolization for Hepatocellular Carcinoma - 6 Month Interim Safety and Efficacy and 3 Month Liver Volume Results from a First in Human Trial. Presented at the 2024 Society for Interventional Radiology Annual Meeting. March 23-28, 2024; Salt Lake City, UT