During anti-tumor treatment development, imaging modalities, criteria, and regulators’ expectations change frequently. Without the direction of imaging scientists who work day in and day out in clinical trial imaging, it would be difficult, if not impossible to keep track of and react to changes during these critical and oftentimes, lengthy trials.

Successful medical imaging in solid tumor trials requires professionals with therapeutic experience, expertise in the modalities required to demonstrate safety and efficacy, and first-hand insight into what global regulators will look for in your submissions.

Here we present examples of scientific advances and regulatory changes that are currently impacting anti-tumor treatment research, demonstrating the need for an imaging partner who is immersed in the regulations, scientific learnings, and trends that could impact the success of your development program.

Example 1: Prostate Cancer

In prostate cancer research, PSMA-PET tracers are now commonly accepted for the detection of metastatic disease that was previously not visible on conventional imaging with CT/MRI and 99mTC Bone Scan. Patients and investigators are reluctant to perform conventional imaging with CT or MRI plus 99mTc bone scan when the more reliable and sensitive PSMA exams reveal more information about treatment efficacy or lack thereof.

Sponsors currently developing prostate cancer treatments are facing severe challenges in study design and meeting their protocol-defined endpoints based on conventional imaging alone. Even worse, as these pivotal trials take several years to complete, the modality and method of CT/MRI plus 99mTc Bone Scan may be outdated and no longer acceptable by the time the study closes.

In addition, there are several PSMA tracers available, they are similar yet not equal in their sensitivity and have slightly different uptake specifics. Plus, not all of these tracers are ready to be used in trials nor approved or available across different continents and countries.

Calyx Medical Imaging has supported the approval of over 140 solid tumor treatment approvals, including this example of a phase III prostate cancer trial which led to the approval of a new treatment option for patients with mCRPC.

Example 2: Immuno-oncology research

Another example is related to the advances we’re seeing in immuno-oncology research. Recent findings are driving modifications to established imaging criteria, as evidenced in a Journal for ImmunoTherapy of Cancer paper (2022), marking the first time immune-related criteria show a correlation with overall survival as the most meaningful endpoint in the treatment of cancer patients.

A recent paper demonstrates irRECIST may provide more clinically relevant information and better treatment decision-making options than RECIST 1.1 alone in solid tumor image assessment.

Because immune-targeted treatment can initially cause a tumor to look as if it is progressing when it is not, clinical trial sponsors using RECIST 1.1 to assess treatment response may end up discontinuing patients who would otherwise remain in the study. Based on data from 1765 patients with 12 types of advanced solid tumors treated with avelumab monotherapy, the study found that irRECIST may provide more clinically relevant information and better treatment decision-making options than RECIST 1.1 alone in solid tumor image assessment.

As a result, Dr. Oliver Bohnsack (see sidebar) suggests that irRECIST can and should replace outdated RECIST 1.1 on all solid tumor trials going forward.

Calyx’s Dr. Oliver Bohnsack leverages his knowledge from having co-authored the immune-related response criteria (irRC, 2009), served as first author of irRECIST (2014), and co-authored Comparison of Assessments using RECIST and irRECIST by Manitz J. et al. (2020) as he designs and implements optimal imaging strategies for Calyx’s customers developing new oncology treatments

Solid Tumor Trials: Maintain More Patients with irRECIST

Calyx Medical Imaging extends groundbreaking capability from Ceretype to improve psychiatric treatment outcomes

Nottingham, England and Morrisville, NC – April 4, 2023 Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced a strategic partnership with Ceretype Neuromedicine, Inc., whose novel functional MRI (fMRI) platform incorporates optimal image acquisition and advanced analytics to de-risk and accelerate the development of psychiatric and neurological therapies.

The current lack of objective biomarkers presents a real challenge for researchers developing treatments for depression/anxiety, schizophrenia, and other neurological/psychiatric conditions such as Parkinson’s Disease. An in-market, audit-cleared “biomarker engine,” the Ceretype platform utilizes cutting-edge fMRI and artificial intelligence (AI) to connect neural circuitry to patient behaviors and treatment outcomes, delivering the objective biologic endpoints researchers need for more precise measurement of treatment effects during central nervous system (CNS) drug development.

“A key component of Calyx’s strategy is partnering with best-in-class technology providers to offer the innovative imaging biomarkers required to find new treatments for unmet medical needs,” said Stephen M. Bravo, MD, Chief Medical Officer at Calyx. “We’re excited to partner with Ceretype and for our customers to leverage their advanced fMRI technology to bring new and more effective psychiatric treatments to market.”

“We’re delighted to combine Ceretype’s neuroscience, biophysics, and computing expertise with Calyx’s 25 years of experience delivering reliable clinical trial imaging,” said Emily Stern, CEO at Ceretype. “Through this partnership, we will achieve our mission of improving psychiatric and neurologic patient outcomes through precision drug development and precision treatment.”

For more information visit Calyx.ai/Imaging and ceretype.com.

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

CTMS | EDC | IRT | Medical Imaging | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.

About Ceretype, Inc.

Ceretype provides actionable insights on brain function – both for individuals and for populations. Our platform de-risks and accelerates clinical trials targeting therapeutics for the central nervous system.  Whole-brain, circuit-level, actionable insights, (e.g., identification of mechanism of action, target engagement, positive response profiles) are delivered across all trial phases, for any intervention and for any neurological or psychiatric disease.  In addition to clinical trials, Ceretype will bring our technology and treatment-specific biomarkers to patients for biologically informed, personalized patient care.

Christine Tobin | Christine.Tobin@Calyx.ai | +1 412-628-8598

When medical imaging is used as a clinical trial biomarker, it’s critical that you select a centralized core lab provider whose experience, capabilities, and approach to medical imaging will help you meet your development objectives, whatever they are.

This applies whether you’re a small biotech needing reliable imaging data to demonstrate your compound’s potential as you seek funding to advance your research and/or to license it to a development partner. Or if you’re one of the world’s largest pharmaceutical companies needing data from a pivotal phase III study to demonstrate safety and efficacy as you seek regulatory approval. And every scenario in between.

Regardless of your objectives, when imaging data will make the difference between success and failure, you can trust Calyx Medical Imaging to help you succeed. Here we present different scenarios in which the scientific expertise, operational experience, and dedication of Calyx’s Medical Imaging team helped researchers on completely opposite ends of the clinical development spectrum achieve their development goals.

Case Study 1:

Small biotech – Early-stage research on rare neurological disease compound

A small biotech company was at the very early stages of investigating a compound for a rare neurological disease for which no approved treatments were available. The company needed an imaging partner with neurological expertise to help them characterize and determine the best modality for measuring disease progression and, eventually, the compound’s efficacy.

After talking to other imaging providers and finding their ‘cookie cutter’ approach not suitable to their research objectives, the company chose to partner with Calyx. The company valued Calyx’s expertise and ability to offer the customized services they needed to move forward in their research.

The relationship began with collaboration between Calyx Medical Imaging experts and the company’s scientific and medical team in compiling and reviewing all available data on the disease presentation, focusing on how medical imaging (MRI, CT) and pathology had been used to diagnose and track disease progression to date.

Calyx scientists then developed a briefing book which presented two imaging-based models of the disease progression and the role medical imaging would play in drug development. The briefing book was ‘FDA ready’ and as such, the company received regulatory approval to move forward.

Continuing the partnership on research of the rare disease, the company contracted Calyx for a natural history study to collect data on the disease presentation and progression for future development of novel therapies. Magnetic Resonance Imaging (MRI) was utilized to develop and evaluate imaging-based biomarkers for assessing the burden and tracking the natural history of this rare disease.

The findings from the natural history study guided and informed the client on the imaging-supported endpoints to be used in their Phase 2 clinical trial on a therapy/compound for the rare disease.

The company continued to rely on Calyx for the design and execution of the phase 2 and natural history studies, which involved Calyx’s standard imaging services and operations, including the development of an independent review charter, training of site personnel on image acquisition, and selection / training of neuroradiologists. In addition to performing thorough quality checks of images captured in the study, Calyx’s Medical Imaging team quickly responded to questions that arose during imaging reads and took an additional, hands-on approach with reviewers and the company’s scientists to ensure the quality of the read results.

During an investors’ event the company shared the promising data – the majority of which were the first to characterize the disease state – as well as updates on the natural history study and their plans to develop the compound further. The data and the rapid progress of the ongoing study were well received by the investors, which enabled the company to continue its research. In the word’s of the company’s VP, Clinical Development Sciences, “We could not have achieved this important milestone without Calyx’s support.”

Case Study 2:

Top five pharma – Phase III trial of prostate cancer treatment

One of the world’s top five pharmaceutical companies was in the late stages of development for a new treatment for metastatic, castration-resistant prostate cancer (mCRPC). Because this advanced form of prostate cancer doesn’t respond well to currently available treatments, mCRPC presents itself particularly challenging for patients and medical professionals alike.

The company selected Calyx Medical Imaging to support its pivotal Phase III trial, which enrolled over 900 patients from over 150 worldwide investigative sites. The imaging data collected throughout the four-year study would support the sponsor’s primary efficacy endpoint and be included in their submission for EU regulatory approval.

For this study, Calyx designed and delivered robust Medical Imaging services that included:

A comprehensive imaging charter, following the Prostate Cancer Working Group 3 (PCWG3) criteria, developed by Calyx’s professional medical writing team.

  • Proven, scalable services to drive the collection of CTs, MRIs, and bone scans, which involved:
    • Training of investigative sites on the correct image capture procedures
    • Collection and quality review of over 22,000 CTs, MRIs, and Bone Scans
  • Advanced internal processes to rule out false positives in bone scans
  • Blinded Independent Central Review (BICR) of imaging reads by 20 expert reviewers
  • A dedicated scientific/medical team with expertise across multiple oncology indications and imaging modalities

Calyx’s scientific and medical team (SciMed) remained intact over the four-year study, consulting with the sponsor and supporting the investigative sites and reviewers throughout to ensure the data derived from the important imaging analysis was of the highest quality.

Calyx met all the deliverable dates throughout the study and supplied reliable imaging data to support the study’s primary efficacy endpoint, demonstrating that the treatment significantly reduced the risk of disease progression or death compared to traditional treatment approaches.

As a result of this study the robust and reliable data supplied by Calyx Medical Imaging, the new and better treatment was approved in the EU and is now giving patients a safe and more effective treatment option for mCRPC.


Photo taken in Helsinki, Finland

Medical Imaging in Rare Disease Trials: Idiopathic Pulmonary Fibrosis (IPF)

Image 177

Managing a Breakthrough: Navigating the Operational Challenges of Breakthrough Trial Imaging


Partnering for Rare Disease Clinical Trial Success

In the USA, a rare disease is defined as one that affects no more than 200,000 individuals nationwide (a prevalence of roughly six per 10,000), and in Europe as one that affects five per 10 000, or around 250,000 individuals. Most current treatments are supportive rather than disease-modifying, leaving the majority of rare disease patients with considerable unmet medical needs.

The design and delivery of clinical trials in the rare disease arena bring specific considerations and potential pitfalls for researchers, patients, pharmaceutical companies, and regulators. Examples of trial-related questions/issues that need to be addressed include recruitment targets, dropout rates, and, ultimately, challenges of regulatory approval if the criteria for efficacy and safety are met.

As a requirement, most rare disease clinical trials are multicentre, and often multinational for sufficient patient recruitment, even in phase I and II trials. This can challenge clinical study protocol harmonization, the selection of appropriate biomarkers, ethical review, site IRB approval, indemnity, organization of clinical services, standards of care, and cultural diversity.

Additionally, while it’s true that every patient matters in all clinical trials, this takes on new meaning in studies of rare diseases. As there are not many people living with the diagnosis, finding patients and keeping them engaged in clinical trials is critical. Trial sponsors can’t risk a patient dropping out of a study because of missteps or problems with data collection and reporting during investigator visits.
As a result, the development of new treatments for rare disease poses unique challenges to clinical trial sponsors. Because these trials can’t risk anything going wrong, sponsors need experienced partners they can rely on to get it right the first time – and every time.

Below is a collection of materials that highlight Calyx’s experience in supporting rare disease clinical trials and how our scientific and technical expertise is helping researchers successfully develop novel treatments to bring new hope to patients living with rare disease.



Special Considerations for RTSM in Rare Disease Trials: Site/Patient Numbers and Reducing Wastage

Photo taken in Helsinki, Finland

Medical Imaging in Rare Disease Trials: Idiopathic Pulmonary Fibrosis (IPF)


150 Orphan Drug Indication Approvals Trusted to Calyx IRT


Medical Imaging in Rare Disease Trials: Eosinophilic Esophagitis (EoE)


Medical Imaging in Rare Disease Trials: Hypertrophic Obstructive Cardiomyopathy (HOCM)


RTSM Considerations in Rare Disease Trials: Study Length and Individualized Therapies

Contact hello@calyx.ai to learn how the expertise and experience behind Calyx’s eClinical solutions can help your rare disease trial succeed.

2022 brought many healthcare advances and opportunities for life science professionals to stay up to date on the research, technologies, and processes that are driving change in how new medical treatments are developed and ultimately approved for worldwide use.

So here, in case you missed them, are the most sought-after articles, white papers, webinars, and more produced by Calyx scientific, technical, and regulatory experts this year. Each provides direction and perspective on optimizing and accelerating the clinical development and approval of medical treatments. We hope you find them as insightful and valuable to you now as they were the first time around.

This blog series addresses the trigger points for unintentional unblinding, how partial unblinding can become full unblinding, and some controversial issues related to unintentional and partial unblinding in clinical trials.

In 2021, Calyx advanced its strategy of partnering with best-in-class technology providers to offer innovative imaging biomarkers required to find new treatments for unmet medical needs. Our groundbreaking partnership with Qynapse enables our clients to more confidently assess the full potential of treatments in development for Multiple Sclerosis, Parkinson’s, Alzheimer’s, and Huntington’s disease, as well as other neurodegenerative disorders. And our partnership with Neosoma delivers novel, improved AI-based neuro-oncology imaging assessment to clinical trial sponsors developing new treatments for gliobastoma and other life-threatening neuro-oncological diseases.

The Journal for ImmunoTherapy of Cancer recently published ‘Comparison of tumor assessments using RECIST 1.1 and irRECIST, and association with overall survival,’ marking the first time immune-related criteria show correlation with Overall Survival as its most meaningful endpoint in the treatment of cancer patients.

The publication demonstrates the benefit to a subgroup of patients who otherwise would have foregone treatment and survival benefit when relying solely on RECIST 1.1 instead of irRECIST, as irRECIST takes the entire tumor burden including new tumor growth into consideration.

In this webinar, co-authors Peter Eggleton of Merck and Oliver Bohnsack of Calyx – leading experts on RECIST and irRECIST – discuss the implications of these findings, what it means for oncology clinical development and treatment decision-making, and why irRECIST easily can and shall replace outdated RECIST 1.1 on all solid tumor trials going forward.

In rare disease trials, it is critical that trial supplies are available when patients are identified, and that drug overage is minimized – a real challenge due to larger numbers of investigative sites typically required to meet trial enrollment levels. Which is why we’re honored that so many sponsors of orphan drug-designated trials have entrusted their RTSM needs to Calyx IRT and continue to rely on our expertise as they bring safe and effective treatments to patients in critical need.  Learn more about Calyx IRT.

This blog series reviews the factors regulatory affairs professionals should consider as they prepare for eCTD 4.0 implementation, beginning with people and business processes, the impacts of new concepts and terminologies, and the challenges to be expected.

What are the consequences of deferring IRT functionality to meet clinical trial start dates? In this Applied Clinical Trials article, Calyx’s Craig Mooney reviews the inefficiencies and potential quality / regulatory risks likely to occur.

At Calyx, we have a long history as part of a CRO, so we know how a CRO functions, the challenges you’re up against, and the importance of keeping your customers satisfied. This inside knowledge affects every aspect of our CRO relationships and makes us more efficient and easier to work with.

Our Activate Solutions for CRO Partners Program enables CROs of all shapes and sizes to partner with Calyx and extend our advanced technology and proven services to drive success for their customers. In 2022 we added more CROs to the program – get to know some of them and learn how they’re partnering with Calyx to deliver more value.

80 sites enrolling 150 patients: How do you minimize overage without burdening your supply team? Learn how one of Calyx IRT’s advanced trial management options solved the complex in this case study.

In this episode of the Calyx Café, Patient Advocate Emily Epstein discusses the importance of supporting clinical trial patients’ mental health and the impact that clinical trial technologies – including DCTs – may have on patient welfare.

Your clinical trials deserve every chance to succeed. And your monitors deserve the most effective tools to improve trial efficiencies. This brochure describes why Calyx CTMS is the solution.

Partnership with Neosoma enables faster, more precise tumor assessment in glioblastoma research.

Nottingham, England and Morrisville, NC – November 17, 2022 – Calyx, the eClinical and Regulatory solutions and services provider relied on for solving complex data challenges in clinical research, today announced a strategic partnership with Neosoma, Inc., an innovative medical technology company focused on advancing brain cancer treatment. Through this partnership, Calyx Medical Imaging extends Neosoma HGG (High-Grade Glioma), a novel AI-based neuro-oncology software device to its worldwide customers who are developing treatments for glioblastoma, the most common and challenging, malignant primary brain cancer.

“Neosoma’s expertise in AI imaging development nicely complements Calyx’s two decades of experience in clinical trial imaging and the insights we’ve gleaned from having successfully supported nearly 100 neuro-oncology clinical trials,” said Stephen Bravo, MD, Chief Medical Officer, Calyx. “We’re pleased to extend Neosoma’s innovation to clinical development and give our customers greater confidence that the important imaging data they depend on to evaluate their glioblastoma compounds’ effectiveness is accurate and reliable.”

Clinical trials of glioblastoma treatments are complex, largely because gliomas have highly irregular and infiltrating shapes that are difficult even for experienced neuro-radiologists to delineate. Volumetric tumor assessments – which are becoming commonly used as exploratory endpoints – currently need to be conducted manually by neuroradiologists, which presents a time-consuming and difficult challenge for glioma image analysis in clinical trials. Leveraging advanced artificial intelligence, Neosoma HGG has been shown to achieve 95.5% accuracy in tumor volume measurement as established by consensus reads, which exceeds that of individual neuro-radiology experts and can save time while generating consistent, automated volumetric assessments of tumor change.

“Calyx’s Medical Imaging team is widely recognized as the leader in clinical trial imaging, especially in oncology, where experience and deep therapeutic area expertise are critical,” said Aly Abayazeed, MD, Chief Medical Officer, and Co-founder, Neosoma. ‘We are delighted to provide faster and more precise assessment of high-grade gliomas to their customers to advance glioblastoma trials and ultimately bring improved treatment options to patients with this life-threatening disease.”

This partnership will extend to other AI-based solutions being developed by Neosoma and reflects Calyx’s strategy of partnering with best-in-class technology providers to offer innovative imaging biomarkers required to find new treatments for unmet medical needs.

For more information on Calyx Medical Imaging, visit Calyx.ai/Imaging

About Calyx

Through innovative eClinical and Regulatory solutions and services, Calyx turns the uncertain into the reliable, helping bring new medical treatments to market reliably. With deep expertise in clinical development and 30 years supporting trial sponsors and clinical research organizations, Calyx harnesses its intelligence and experience to solve complex problems, deliver fast insights, and get new drugs to market every day.

Medical Imaging | IRT | CTMS | EDC | RIM

Take your trials further with intelligent insights at Calyx.ai or at LinkedIn, Twitter, or Facebook.


Christine Tobin | Christine.Tobin@Calyx.ai | +1 412-628-8598

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