Radiopharmaceuticals

Clarity and PSI Kick Off SAR-bisPSMA Phase III

PSI CRO, 26 October 2023 — Clarity Pharmaceuticals (ASX: CU6) (“Clarity”), a clinical stage radiopharmaceutical company with a mission to develop next-generation products that improve treatment outcomes for children and adults with cancer, and PSI CRO AG (“PSI”), a global contract research organisation committed to on-time enrollment in radiopharmaceutical clinical trials, have entered into an agreement and have commenced work towards Clarity’s Phase III diagnostic trial of SAR-bisPSMA in prostate cancer participants, CLARIFY (NCT06056830)1.

CLARIFY derives from “Positron Emission Tomography using 64Cu-SAR-bisPSMA in participants with high-risk prostate cancer prior to radical prostatectomy: A prospective, single-arm, multi-centre, blinded-review, Phase III diagnostic performance study”. It is a non-randomised, open-label clinical trial in 383 participants.

The aim of the Phase III trial is to assess the diagnostic performance of 64Cu-SAR-bisPSMA PET to detect prostate cancer within lymph nodes located in the pelvic region. Evaluation will take place over 2 imaging timepoints, Day 1 (day of administration) and Day 2 (approximately 24 hours post administration). CLARIFY is expected to begin recruitment in late 2023.

Clarity’s Executive Chairperson, Dr Alan Taylor, commented, “We are very excited to move one step closer to initiating our first registrational Phase III trial. With recent positive and valuable guidance from the US FDA in relation to our 64Cu-SAR-bisPSMA program, we look forward to commencing recruitment into the CLARIFY trial shortly and to gathering more data on this next-generation product to confirm the compelling preclinical and clinical trial results to date.

“The positive results from our completed PROPELLER2 trial showed that 64Cu-SAR-bisPSMA is safe and its uptake in PSMA-expressing cancer lesions was significantly higher compared to an approved standard-of-care PSMA imaging agent for prostate cancer in Australia and the US. This may enable diagnosis of additional and smaller lesions, which we observed in our PROPELLER2 trial, and we are eager to investigate the further benefits of delayed imaging, particularly in this patient population, a characteristic not available to the first generation of PSMA diagnostic agents. Furthermore, we believe that the additional shelf-life of up to 48 hours will not only allow clinics greater flexibility in scheduling of the scans, but also improve patients’ access to care in clinics and geographic areas where the short half-life of current PSMA PET tracers restricts the use of radiopharmaceuticals.”

PSI’s Senior Director of Operations, Rhonda Critchlow, commented, “Using our global database of over 400 radiopharmaceutical sites, we will be able to identify sites with the best resources and capabilities for the CLARIFY trial. We are excited to begin our collaboration with Clarity and will focus on the startup of high-performing sites to achieve the first patient in, in the shortest time possible. We believe that a myriad of clinical, logistical and manufacturing benefits of Clarity’s Targeted Copper Theranostics platform holds promise of improving treatment outcomes for patients with cancer and look forward to working together on achieving this important goal.”

lymph node scans
Concordant lesions on 64Cu-SAR-bisPSMA (200 MBq) and 68Ga-PSMA-11 PET/CT consistently showed higher SUVmax, SUVmean and tumor to background ratio with 64Cu-SAR-bisPSMA compared to 68Ga-PSMA-11. SUV: standardized uptake value. PROPELLER study.
Readers did not detect uptake in pelvic lymph nodes on the 68Ga-PSMA-11 PET/CT (Top). PET/CT demonstrated uptake of 64Cu-SAR-bisPSMA (Bottom) in a left pelvic lymph node according to both Readers. Prostate cancer was confirmed via histopathology. Arrows highlight the node detected on 64Cu-SAR-bisPSMA PET/CT. PROPELLER study.

About SAR-bisPSMA: SAR-bisPSMA derives its name from the word “bis”, which reflects a novel approach of connecting two PSMA-targeting agents to Clarity’s proprietary sarcophagine (SAR) technology that securely holds copper isotopes inside a cage-like structure, called a chelator. Unlike other commercially available chelators, the SAR technology prevents copper leakage into the body. SAR-bisPSMA is a TCT that can be used with isotopes of copper-64 (Cu-64 or 64Cu) for imaging and copper-67 (Cu-67 or 67Cu) for therapy.

64Cu-SAR-bisPSMA and 67Cu-SAR-bisPSMA are unregistered products. Individual results may not represent the overall safety and efficacy of the products. The data outlined in this announcement has not been assessed by health authorities such as the US Food and Drug Administration (FDA). A clinical development program is currently underway to assess the efficacy and safety of these products. There is no guarantee that these products will become commercially available.

About Prostate Cancer: Prostate cancer is the second most common cancer diagnosed in men globally and the fifth leading cause of cancer death worldwide3. The American Cancer Institute estimates in 2023 there will be 288,300 new cases of prostate cancer in the US and around 34,700 deaths from the disease4.

About Clarity Pharmaceuticals: Clarity is a clinical stage radiopharmaceutical company focused on the treatment of serious disease. The Company is a leader in innovative radiopharmaceuticals, developing targeted copper theranostics based on its SAR Technology Platform for the treatment of cancer in children and adults.

www.claritypharmaceuticals.com

About PSI: PSI CRO is a privately-owned, full-service clinical research organization (CRO) operating globally. PSI’s global reach supports clinical trials across multiple countries and continents and specializes in the planning and execution of global pivotal registration clinical trials. With an exceptionally high repeat and referral business rate combined with minimal staff turnover, PSI is committed to being the best CRO in the world as measured by its employees, customers, investigators, and vendors.

References

1Positron Emission Tomography Using 64Cu-SAR-bisPSMA in Participants With High-risk Prostate Cancer Prior to Radical Prostatectomy: A Prospective, Single-arm, Multi-center, Blinded-review, Phase 3 Diagnostic Performance Study – CLARIFY. ClinicalTrials.gov ID NCT06056830.

2Lengyelova E, Wong V, Lenzo N, Parker M, Emmett L. 64Cu-SAR-bisPSMA (PROPELLER) positron emission tomography (PET) imaging in patients with confirmed prostate cancer. ASCO 2023. Poster available at: claritypharmaceuticals.com/pipeline/scientific_presentations

3Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21660

4American Cancer Society: Key Statistics for Prostate Cancer, https://www.cancer.org/cancer/prostate-cancer/about/key-statistics.html

For more information, please contact:

Clarity Pharmaceuticals
Dr. Alan Taylor
Executive Chairman
ataylor@claritypharm.com

Catherine Strong
Investor/ Media Relations
cstrong@citadelmagnus.com
+61 406 759 268

Clarity and PSI Kick Off SAR-bisPSMA Phase III Read More »

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Case Study: Phase 3 Radiopharmaceutical Clinical Trial in Oncology

At a Glance: FDA Approval in 4 Years

Radiopharmaceutical clinical trials face a host of logistical challenges from startup through the clinical phase. A sponsor of a pivotal Phase 3 prostate cancer study investigating a radiopharm product approached PSI for support based on our experience and established network of over 400 global radiopharmaceutical sites. By working closely with our sites and vendors, PSI met or beat all critical milestones, helping our client secure FDA approval for their radiopharmaceutical product in under four years.

graph representing predicted vs. actual patient enrollment and patient screening numbers
Patient Screening and Enrollment Numbers
key metrics for radiopharmacy case study. 1200 patients with heart in hand symbol. 860 trial sites with a target in a human head symbol. 10 countries with a world symbol. 90 trial sites with a hospital symbol. all in white text.

Sponsor Challenges

The major challenges in global nuclear medicine trials include the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. The investigational product in this study had a half-life of three days, necessitating diligent time management and site engagement to deliver the study on schedule.

PSI Strategy

To make sure eligible patients didn’t miss these three-day windows, PSI’s CRAs encouraged sites to maintain frequently updated pre-screening logs and regularly discuss the pool of potential patients with the investigators. We also worked closely with sites and the manufacturing facilities to time the inclusion of each patient appropriately, especially around local bank holidays when a manufacturing facility would not be available.

Results

1) Expedited Study Timelines
PSI met or beat all critical milestones during the study, including achieving FPI in the US in less than 3 months and completing NDA submission one month ahead of schedule.

2) 99% Enrolling Sites
Only one out of all initiated sites did not enroll a patient.

3) Successful Regulatory Approval
After passing three FDA inspections without major findings, PSI’s regulatory experts helped our client secure FDA approval in under four years.

“I would personally like to acknowledge and thank the entire PSI team and leadership for the dedication, perseverance and determined support that supported the early completion of the study. Your team have showcased all the capabilities and attributes of a best-in-class CRO for project delivery.”
abstract background purple cells
--Global Head
External Relationship Management

About Us

For 25 years, we have built trusted relationships with biotech sponsors, with 90% of our customers being repeat and referral. 

Therapeutic Areas

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Global Reach

Clinical trial sponsors working in oncology, hematology, IBD, infectious diseases, multiple sclerosis, and many rare diseases rely on PSI’s guidance and experience. 

Case Study: Phase 3 Radiopharmaceutical Clinical Trial in Oncology Read More »

radiopharmaceutical molecules, glass-like on an light blue background

Operationalizing Radiopharmaceutical Clinical Trials: Opportunities and Challenges  

When PSI published a blog post on the current state of radiopharmaceutical clinical trials in 2019, we had no way of knowing of the changes that would transform the clinical trial industry – along with every other one on earth – just a few months later.

Of course, managing global nuclear medicine trials has never been easy due to the complexity of regulatory requirements in each country and the necessity for experienced, highly trained sites either within close proximity to the material’s manufacturing site or with the ability to provide at the site level. However, travel restrictions and supply chain challenges have only exacerbated these obstacles. While some of these issues are starting to ease, the need for an experienced, global perspective toward managing these studies has only increased.

Success starts with understanding the risk factors that can impact your radiopharmaceutical trial from startup through the clinical phase. Drawing on our experience as we continue to run radiopharm studies in multiple oncology indications, we’ve highlighted some of the most common challenges to consider below – and how to overcome them.

1. Country-specific Regulatory Requirements for Radiopharmaceutical Agents

As development interest in this new class of agents has continued to grow, so has the complexity of the regulatory landscape. Additional approvals should be considered for studies in both the United States and the United Kingdom, as outlined in the table below:

Country Consideration
USA Radiation Safety Committees approvals typically obtained before submissions to IRBs
UK HRA radiology review prior to submission is needed, as well as approval of Administration of Radioactive Substances Advisory Committee (ARSAC). ARSAC review goes in parallel to the ethics/regulatory review

The European Union’s Clinical Trial Regulation has streamlined the process for submitting clinical trial applications in the EU, but many countries still encourage or require additional approvals. An in-depth understanding of each specific country’s requirements in your trial is essential to proactively anticipate requirements and potential questions that can delay approvals. Drawing on our experience with these studies, PSI maintains a library of country-specific radiopharmaceutical requirements and regulations within VISIONAL™, our machine-learning-powered system for data-driven feasibility and enrollment forecast. This pairing of regulatory expertise and technology allows us to accurately predict timelines and model hundreds of country and site combinations, their budgets, and probability of success within minutes.

2. Site Imaging Qualifications and Other Common Delays in Site Activation

Site qualification can be time-consuming for sites, so sponsors should confirm timelines during the feasibility process and ensure that sites are well-trained and supported with any study-specific calibration or camera requirements. PSI created the role of Site Support Specialist to help support sites in the qualification and camera process as well as during the study, saving them time and frustration. An example of the site imaging qualification process is shown below.

Site Imaging Qualifications

This is a simplified example, and the process can be much lengthier if dosimetry is included as part of the study. We have found having a dedicated Site Support Specialist assigned to work one-on-one with each site during the qualification process significantly decreases delays in site activation due to camera qualification.

Issues with technical transfer, or IND amendments (if the drug will be manufactured on-site), can also lead to delays. In some instances, choosing a central procurement facility may be effective, allowing one facility to execute the contract and technical transfer independent of site startup and activation.

3. Logistical Issues During Clinical Phase

As noted in our previous article, cooperation and coordination are imperative every step of the way for the successful delivery of radiopharmaceutical trials: from the facilities and procedures that produce the nuclear material to their handling and storage to the transportation of the drug and dispensation. Understanding the patient journey and which procedures must be completed at each step, including when the investigational product should be ordered, is recommended as a proactive foundational tool. At PSI, we have developed a detailed and unique visual patient journey utilized at the site and project levels.

In addition, other tools for clinical staff, such as a patient visit and MRI/whole brain PET scan tracker calendar, biopsy procedure schedule, source template, and automatic calculator for time-dependent procedures, will help provide additional clarity and compliance. We also recommend tracking key steps via Interactive Response Technology.

4. Central Radiology Review and Delays in Submitting Scans

It is critical to manage and track all steps in the imaging process at each site, including navigating the technical dialogue between nuclear medicine technologists, nuclear physicians/radiologists, investigators, and other stakeholders. Sponsors should ensure clear communication and receipts from the central reader for all scans received and that the appropriate project team members are copied on any queries to the site. PSI’s Site Support Specialist is key in ensuring every stage is performed accurately and on time, including monitoring site submissions in real time and assisting sites with submissions when needed. This role has also proven beneficial in managing and providing oversight of all site queries, cutting the site team’s time spent on imaging queries in half.

5. Development and Implementation of Site-Specific Enrollment Plans

Solid tumor oncology trials represent one of the most competitive markets in clinical research, with over 3,000 trials ongoing or planned, according to data from clinicaltrials.gov, Citeline, and GlobalData. With additional obstacles presented by sites’ limited proximity to manufacturing centers, sponsors and their partners should have detailed site-specific enrollment plans that consider the patient journey at each site, from identifying prospective patients to scheduling the needed imaging assessments and surgeries or biopsies. Walking through this patient journey helps both the site and the CRA to identify all the involved team members so that potential risk factors can be mitigated. PSI’s dedicated Site Support Specialists may meet with sites as soon as they’re selected by clients to understand this patient journey and put together a tailored site enrollment strategy based on site referral patterns, facilities, capabilities, and other key factors.

Meet the challenge of your radiopharmaceutical pivotal trial with PSI

Every study is different, and there is no one-size-fits-all solution for ensuring success. With an established and proven database of more than 1,000 global radiopharmaceutical sites, PSI specializes in delivering radiopharm studies on time and with quality data. Seventy-nine percent of PSI CRAs have oncology experience, and PSI has developed therapeutic-specific training and resources for radiopharmaceutical trials to achieve the highest level of quality for your study. In addition, PSI’s Site Support Specialist role has led to a dramatic improvement in site activation and enrollment.

Contact us here to learn more about running your pivotal Phase 2 and 3 radiopharmaceutical trials with PSI.

Operationalizing Radiopharmaceutical Clinical Trials: Opportunities and Challenges   Read More »