On June 5, 2025 Clarity Pharmaceuticals (ASX: CU6) ("Clarity" or "Company"), a clinical-stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for patients with cancer, reported positive results from the diagnostic Phase II DISCO trial (NCT04438304)1 with 64Cu-SARTATE in patients with known or suspected NETs (Press release, Clarity Pharmaceuticals, JUN 5, 2025, View Source [SID1234653737]).
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DISCO trial design
DISCO is a "Diagnostic Imaging Study of 64COpper-SARTATE Using PET on Patients with Known or Suspected Neuroendocrine Tumours". It assessed the performance of Clarity’s SARTATE imaging product as a potential new method to diagnose and manage NETs. The trial aimed to build on earlier clinical experience with 64Cu-SARTATE in patients with NETs, which demonstrated that the diagnostic has excellent imaging characteristics and suggested that 64Cu-SARTATE PET/CT provides comparable or superior lesion detection to 68Ga-DOTATATE PET/CT in all patients, especially in the liver2.
DISCO recruited participants with Gastroenteropancreatic NETs (GEP-NETs) across 4 sites in Australia, comparing the diagnostic performance of 64Cu-SARTATE PET at an average of 4 hours (between 3 and 5 hours) and approximately 20 hours post-administration (same-day and next-day imaging, respectively) to the current SOC, 68Ga-DOTATATE PET. Participants were required to have undergone a pre-study 68Ga-DOTATATE PET/CT scan within 5 weeks, but not closer than 6 hours prior to the administration of 64Cu-SARTATE as part of their routine clinical care.
The trial was initially designed to enrol up to 63 patients, based on the anticipated lesion-level discordance rate between 64Cu-SARTATE and 68Ga-DOTATATE PET. Following a pre-planned early analysis of the data collected during the study, the sample size was adjusted to 45 patients, allowing for an earlier enrolment completion.
Study participants were dosed with 200 MBq of 64Cu-SARTATE. Both the 64Cu-SARTATE and 68Ga-DOTATATE PET/CT scans were reviewed by 2 blinded central readers. Participants were followed for up to 12 months to complete additional investigations (e.g. biopsy and conventional imaging) and obtain the SOT used to verify discordant findings between the scan pairs. The verification of discordant findings against the SOT evidence (as true- or false-positive findings) was completed by an independent central assessor, distinct from the central readers evaluating the 64Cu-SARTATE and 68Ga-DOTATATE scans. Lesion-level sensitivity was calculated for the discordant lesions between the scan pairs, with each true-positive discordant lesion on one scan considered a false-negative lesion on the other scan, and each false-positive discordant lesion on one scan considered a true-negative lesion on the other scan.
Topline results
The results indicate that lesion detection by 64Cu-SARTATE (regardless of imaging timepoint) substantially outperformed that of 68Ga-DOTATATE. 64Cu-SARTATE detected 393 to 488 lesions, and 68Ga-DOTATATE identified 186 to 265 lesions among 45 participants across the readers.
Figure 1: 59-year-old participant with functional NETs. 68Ga-DOTATATE PET/CT was performed 26 days prior to the 64Cu-SARTATE PET/CT (same-day imaging). PET (top images): top left image shows higher background on the 68Ga-DOTATATE PET. Top centre and right PET images show multiple lesions detected by 64Cu-SARTATE against a low background. Images are shown as maximum intensity projections. PET/CT fusion (bottom images): axial sections show intense liver uptake on the 68Ga-DOTATATE PET/CT (bottom left), which limits the ability to distinguish lesions from the background, and 3 clearly defined lesions are visible on the 64Cu-SARTATE PET/CT (arrows; bottom centre and right images, same-day and next-day imaging, respectively). Mean maximum standardised uptake value (SUVmax) of lesions shown in the 64Cu-SARTATE PET/CT images: 16.1 and 16.5 on same-day and next-day imaging, respectively. Lesions in the liver have been verified as true-positive based on other scans, including diagnostic CT and magnetic resonance imaging (MRI). Fused images are shown with consistent scaling for visual comparison.
Out of all lesions identified by the readers, 230-251 were deemed to be discordant between 64Cu-SARTATE and 68Ga-DOTATATE PET/CT, with 93.5% (average across readers and imaging days) of these discordant lesions detected on the 64Cu-SARTATE scans only. A previously completed Phase I study demonstrated a 1.7 fold increase (median of 6.70 vs. 3.92, p=0.002) in contrast (i.e. lesion-to-background ratio) for 64Cu-SARTATE PET/CT performed at 4 hours post-administration compared to 68Ga-DOTATATE PET/CT2. This improvement in contrast may explain the detection of additional lesions observed in the DISCO trial. The average SUVmax, representing the highest concentration of 64Cu-SARTATE uptake in lesions, was notably high, ranging from 37.42 to 43.90 across both imaging days in the DISCO trial.
Approximately half of all discordant lesions had an available SOT, which yielded a lesion-level sensitivity of 93.4% to 95.6% (95%CI: 65.1, 99.5) for 64Cu-SARTATE, including both timepoints, and only 4.4% to 6.6% (95%CI: 0.5, 34.9) for 68Ga-DOTATATE.
64Cu-SARTATE was deemed safe and well tolerated. Only 7 (15.6%) trial participants experienced 64Cu-SARTATE-related AEs, the majority of which were mild (Grade 1) gastrointestinal events, commonly observed in NET patients, and typically resolved within 2 days of onset. No serious treatment-emergent AEs were observed in the study.
Based on the findings of the DISCO trial to date, Clarity will commence the next steps to conduct a registrational Phase III study of 64Cu-SARTATE in NETs with the US FDA’s guidance.
Clarity’s Executive Chairperson, Dr Alan Taylor, commented, "We are very excited about the initial topline data from the DISCO trial as 64Cu-SARTATE was confirmed to be safe and very effective in detecting NET lesions in patients with known or suspected disease. The DISCO trial demonstrates a significant advantage of our diagnostic over 68Ga-DOTATATE. 64Cu-SARTATE detected almost double the number of lesions compared to the SOC, and, where SOT was available, a very high lesion-level sensitivity of 93.4% – 95.6% in comparison to just 4.4% – 6.6% for 68Ga-DOTATATE for these discordant findings. In addition to identifying more lesions with our product, lesions detected by 64Cu-SARTATE also exhibited high uptake with low background on the PET scans, making it easier to identify those lesions by readers. Excellent lesion visualisation was also supported by substantial clearance from the liver. The favourable biodistribution of 64Cu-SARTATE PET enabled high-contrast diagnostic imaging for up to approximately 24 hours post-injection (Figure 1), offering greater flexibility in the scheduling of PET/CT scans.
"In the DISCO trial, we continue to observe the substantial limitations of the current-generation of short half-life isotope products, what we call isotope-centric medicine. This is clearly illustrated by 68Ga-DOTATATE with imaging timepoints solely dictated by the very short isotope half-life (approximately 1 hour for gallium-68) as opposed to good science and medicine. In contrast, 64Cu-SARTATE highlights the extraordinary benefits of next-generation patient-centric medicine, where imaging is guided by the optimal timepoint to scan and detect lesions, focusing on the needs of the patients and their treating professionals.
"We believe that the flexibility of imaging with 64Cu-SARTATE, in comparison to approximately 1 hour with 68Ga-DOTATATE, plays an important role in the detection benefits seen in the DISCO study. We have known this for many years and have demonstrated these advantages of optimal timepoint imaging with different products in our Targeted Copper Theranostic (TCT) platform, including SARTATE. We have seen first-hand in a number of clinical trials that once radiopharmaceutical products are administered, they take time to find the lesion whilst also needing to clear from non-target organs, providing greater contrast. This is known as signal-to-noise ratio or, in our case, tumour-to-background ratio. Having greater contrast is especially important to identify smaller or more difficult to find cancers.
"The longer half-life of copper-64, combined with Clarity’s proprietary SAR Technology, sets up a strong foundation for next-generation diagnostics, which could be unmatched in the radiopharmaceutical sector. In addition to clinical benefits, the opportunity for high-volume centralised manufacturing and broad, on-demand distribution of ready-to-use diagnostics translates into flexibility and reliability for patients and their treating staff, meaning that every patient with access to PET imaging, including those in underserved and broad geographic areas, may access improved cancer diagnostics.
"Patients with NETs are often misdiagnosed and experience delays in receiving the correct diagnosis, which may lead to disease progression and identification of their cancer at later stages. Visualising NET lesions earlier and more accurately may have a significant impact on patient outcomes as it equips clinicians with crucial information on disease burden, helping to determine an optimal treatment plan. As such, the SSTR2 imaging market is an important focus for Clarity. We estimate the NET diagnostic market in the US alone to be around 100,000 scans per year, growing to approximately 120,000 scans per year by 2029.
"Importantly, the positive results of the DISCO trial open broader opportunities for the development of 64Cu-SARTATE in additional SSTR2-expressing malignancies beyond NETs, such as certain types of breast and lung cancers, where unmet clinical needs remain high. We believe the SSTR2 market is set to grow substantially with a number of therapies in development for this target, which include large indications such as breast and lung cancers. Subject to the successful completion of these studies, we believe that the imaging market for 64Cu-SARTATE could be as large, if not larger, than the very lucrative prostate cancer imaging market where radiopharmaceuticals currently dominate the diagnostic paradigm.
"We look forward to sharing additional data readouts from the trial and presenting the results at future international medical conferences. We plan to rapidly progress discussions with the FDA to initiate a diagnostic registrational Phase III study, as a first key step in expanding SARTATE into the theranostic field of NETs, as well as other SSTR2-expressing cancers, with the copper-64/copper-67 pair. If the findings from the DISCO trial are substantiated in a registrational Phase III study and lead to regulatory approval by the US FDA, 64Cu-SARTATE may play an important role in improving diagnostic accuracy, lesion detection and staging of patients with NETs. These factors could improve clinical decision-making and treatment outcomes, potentially positioning 64Cu-SARTATE as a best-in-class agent for the diagnosis of NETs."
About SARTATE
SARTATE is a next generation, highly targeted theranostic radiopharmaceutical. It is being developed for diagnosing, staging and subsequently treating cancers that express SSTR2, such as NETs. Like all Clarity products, the SARTATE product can be used with copper-64 (64Cu) for imaging (64Cu-SARTATE) or copper-67 (67Cu) for therapy (67Cu-SARTATE).