New Study Demonstrates Safety And Biodistribution Of An Easy Use One-Step Radiopharmaceutical Kit For Prostate Cancer Imaging

Phase I Data For 68Ga-THP-PSMA Published in The Journal of Nuclear Medicine

9th October, 2017, Bracknell, UK – Today, Theragnostics, Ltd., a radiopharmaceuticals company developing products for the diagnosis and treatment of cancer, announce the results of a phase I study evaluating the safety and biodistribution of 68Ga-THP-PSMA PET/CT in patients with prostate cancer, published in The Journal of Nuclear Medicine (JNM).1
Fourteen patients with biopsy proven adenocarcinoma of the prostate took part in the study and were split into two groups. Group A included treatment naïve patients scheduled for surgery (prostatectomy). Group B observed patients with metastatic prostate cancer (represented by demonstration of at least one unequivocal PSMA-avid focus), and compared 68Ga-THP-PSMA PET/CT with standard of care, 68Ga-HBED-PSMA-11 PET/CT.

Results demonstrated that 68Ga-THP-PSMA can be safely administered, with no adverse events recorded in any patients. Uptake seen in the prostate on 68Ga-THP-PSMA PET/CT correlated with histopathologic PSMA expression seen on pathology finding following prostatectomy, highlighting the ability to non-invasively image prostate cancer directly.
PSMA PET has rapidly emerged as practice changing imaging modality with significant advantages compared to conventional imaging such as CT, MRI or bone scanning” says Associate Professor Michael Hofman, and lead investigator of this study. “68Ga-THP-PSMA provides the ability to rapidly manufacture PSMA in the clinic on-demand using a simple kit, and therefore can offer efficiencies to alleviate some of the challenges experienced by clinicians when utilising current alternatives where health services are strained, such as the UK – this may reduce the variation in adoption of this technology across the globe, which is a challenge we face in prostate cancer imaging. This is an important advance in order to make this new scan widely available to men with prostate cancer.”
68Ga-PSMA positron emission tomography/computed tomography (PET/CT) is a non-invasive diagnostic technique to image prostate cancer with increased prostate-specific membrane antigen expression. PSMA is a transmembrane protein primarily present in all prostatic tissues. Increased PSMA expression is seen in a variety of malignancies, most notably in prostate cancer. Adenocarcinomas of the prostate demonstrate PSMA expression in the majority of primary and metastatic lesions.2 68Ga-HBED-PSMA-11 PET/CT has demonstrated clinical utility in both staging of newly diagnosed patients and restaging. More accurate staging of high risk patients may enable better selection of the most appropriate management strategy and avoid futile locoregional surgery or radiotherapy in patients with metastatic disease. 68Ga-THP-PSMA PET/CT is a new radiopharmaceutical with a simplified design for an easy-to-use one-step-kit.

Professor Prokar Dasgupta, Professor and Chair of Urology at King’s College London, Guy’s Hospital, King’s Health Partners comments, “While imaging such as multiparametric MRI has greatly improved the diagnostic and staging pathway in prostate cancer patients, bone scans to detect distant metastasis can often be inaccurate. PSMA PET scanning is fast becoming the imaging modality of choice in high-risk prostate cancer as well as in patients with recurrent disease. Accurate staging, particularly in patients with metastatic disease is absolutely vital. The challenge we face today lies in the cumbersome production of PSMA PET tracer, and so easy, rapid manufacturing would not only be a significant advance, but would also make such scanning widely available to patients.”

68Ga-THP-PSMA can be manufactured quickly using a 68Ga generator and cold-kit vial analogous to procedures widely used for 99mTc radiotracer production, and therefore will enable rapid adoption and may widen the access of PET to prostate cancer patients. 68Ga-THP-PSMA offers labelling in less than five minutes at room temperature. Current alternatives, such as the DOTA or HBED chelator, incorporated in the widely used 68Ga-HEBD-PSMA or 68Ga-DOTATATE requires pH adjustment, heating and cooling, as well as possible purification, requiring significant manual handling and operator radiation dose or use of an automated synthesiser with the possibility of generating a mixture of compounds. The Group B data demonstrated that 68Ga-THP-PSMA is comparable with standard of care, with background physiologic uptake was significantly lower with 68Ga-THP-PSMA compared to 68Ga-HBED-PSMA, whilst not changing the management in these patients, as well as concordance in the number of metastases identified.
We are proud to present the results of this phase I study alongside our colleagues at the Peter MacCallum Cancer Centre and Kings College London”, comments Greg Mullen, CEO, Theragnostics. “These data demonstrate the disruptive technology of 68Ga-THP-PSMA, by simplifying and speeding up current production, while providing increased imaging sensitivity to support the staging of prostate cancer. We are rapidly moving forward with the clinical development of 68Ga-THP-PSMA, and working with regulatory bodies to address an unmet clinical need by bringing this technology to prostate cancer patients.”
Prostate cancer is the most common form of cancer in men across the UK. Over 47,000 men are diagnosed with prostate cancer every year, which equates to 129 men every day.3

About the study
The investigator-initiated prospective study was sponsored by the Peter MacCallum Cancer Centre, and funding was received from Theragnostics Limited. Fourteen patients with biopsy proven adenocarcinoma of the prostate were recruited; eight in Group A and six in Group B. Safety and biodistribution of 68Ga-THP-PSMA were assessed in all patients. In Group A, additional aims were to define whole body radiation dose and plasma radiotracer clearance, and correlate uptake with tumour PSMA expression on histopathology. In Group B, the aim was to compare physiologic and pathologic biodistribution in patients with PSMA-avid malignant disease on 68Ga-HBED-PSMA-11 PET/CT.

In Group A, patients had no prior treatment for prostate carcinoma and were scheduled for prostatectomy. In Group B, inclusion criteria additionally mandated patients with prior clinical 68Ga-HBED-PSMA-11 PET/CT demonstrating at least one unequivocal PSMA-avid focus considered to represent metastatic prostate cancer.
For more information, please visit: http://jnm.snmjournals.org/content/early/recent.

About Theragnostics
Theragnostics is a privately held clinical stage radiopharmaceutical company that is developing a complete portfolio of products for the management and treatment of cancer patients, from initial diagnosis to treatment planning and monitoring, to therapy.

About Peter MacCallum Cancer Centre
Peter Mac is one of the world’s leading cancer research, education and treatment centres globally and is Australia’s only public hospital solely dedicated to caring for people affected by cancer. Over 2,500 staff, including more than 580 laboratory and clinical researchers, all focus on providing better treatments, better care and potential cures for cancer. For more information, please visit www.petermac.org.

About Kings College London
King’s College London is one of the top 25 universities in the world (2017/18 QS World University Rankings) and among the oldest in England. King’s has more than 29,600 students (of whom nearly 11,700 are graduate students) from some 150 countries worldwide, and some 8,000 staff.
King’s has an outstanding reputation for world-class teaching and cutting-edge research. In the 2014 Research Excellence Framework (REF), eighty-four per cent of research at King’s was deemed ‘world-leading’ or ‘internationally excellent’ (3* and 4*).
Since our foundation, King’s students and staff have dedicated themselves in the service of society. King’s will continue to focus on world-leading education, research and service, and will have an increasingly proactive role to play in a more interconnected, complex world. Visit our website to find out more about Vision 2029, King’s strategic vision for the next 12 years to 2029, which will be the 200th anniversary of the founding of the university.
World-changing ideas. Life-changing impact: https://spotlight.kcl.ac.uk/.

References
1. Hofman et al. Cold Kit PSMA PET Imaging: Phase I study of 68Ga-THP-PSMA PET/CT in patients with prostate cancer. Journal of Nuclear Medicine. 2017. Available at: http://jnm.snmjournals.org/content/early/recent.
2. Fendler et al. 68Ga-PSMA PET/CT: Joint EANM and SNMMI procedure guideline for prostate cancer imaging: version 1.0. Eur J Nucl Med Mol Imaging. 2017. Available at: www.eanm.org/content-eanm/uploads/2016/11/EANM_SNMMI_Procedure-guideline-Ga-PSMA.pdf.
3. Prostate Cancer UK. About Prostate Cancer. Available at: prostatecanceruk.org/prostate-information/about-prostate-cancer.