Successful medical imaging in solid tumor trials requires the insight and expertise of professionals who are dedicated to providing imaging core lab services and have therapeutic experience, expertise in the modalities required to demonstrate safety and efficacy, and first-hand insight as to what global regulators will look for in your submissions.
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 prior to study start and First Patient In.
A Look at Changing Regulations in Solid Tumor Research
Your imaging partner needs to be immersed in the scientific advances and regulatory changes that may impact the outcome of your anti-tumor treatment development program, as outlined in the following examples
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as these pivotal trials take several years to complete, the modality and method of CT/MRI plus 99mTc Bone Scan may be outdated and no longer acceptable by the time the study closes.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 across different continents and countries.
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
Example 2: Prostate Cancer
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) markingthe first time immune-related criteria show a correlation with overall survival as the most meaningful endpoint in the treatment of cancer patients. As a result, Dr. Oliver Bonshack (see sidebar) suggests that irRECIST can and should replace outdated RECIST 1.1 on all solid tumor trials going forward.
In Solid Tumor Imaging, Experience Matters
Calyx Medical Imaging scientists have the industry’s most extensive experience in oncology clinical trial imaging and are immersed in their therapeutic areas of expertise and modality specialties. The team of 80+ internal scientific and medical experts has successfully managed the imaging components of over 1,500 clinical trials across 90 unique oncology indications and has supported over 150 solid tumor regulatory approvals involving the entire span of imaging modalities utilized in tumor patient care.
Calyx Medical Imaging Experience
Calyx’s scientists are committed to the success of your clinical trial, maintaining regular contact with your team throughout its duration and overseeing the important independent imaging reads that can make or break your trial. This becomes even more critical when your study-specific needs change, like when regulators question the initial data submitted or request additional information on how reads were conducted. Or, if early results demonstrate superior efficacy and earn your compound fast-track designation, significantly growing and accelerating your imaging needs, most times overnight.
The Value of a Scalable Reviewer Network and Operational Infrastructure
A key component of Calyx’s Medical Imaging offering is the delivery of accurate and precise imaging assessments performed by board-certified experts from a network of over 1,200 independent readers who are well-recognized in their fields. Calyx’s network of readers is active in the clinic and works with patients regularly, ensuring they have a comprehensive and up-to-date understanding of your patients, the disease, and the role of imaging in their assessment.
And, Calyx’s operational model enables our client delivery teams to anticipate your study needs and scale our services to deliver quick and reliable continuity of service with efficient setup of sites and reduced imaging queries to meet your trial timelines, even during mid-study changes.
Having access to so many retained, experienced radiologists – the majority of whom have worked with Calyx for over a decade – and deep operational expertise delivered through seven global locations centered in key life science hubs, Calyx Medical Imaging delivers the flexibility and scalability trial sponsors need during all stages of solid tumor treatment development, helping them to overcome challenges and tackle unexpected trial changes as evidenced in the following case studies.
Calyx Medical Imaging:
By the Numbers
450,000+
ANNUAL READS FROM GLOBAL SITES
4.6M
TOTAL IMAGES PROCESSED
<24-HR
CASE RESOLUTION (80K ANNUAL CASES)
50+
STUDIES WITH >10K TIMEPOINTS
120+
STUDIES WITH >1K PATIENTS
575+
STUDIES WITH <100 PATIENTS
Case Study: Scaling to Support Melanoma PD1/PDL1 Breakthrough Trial
A client approached Calyx Medical Imaging for support with a PD1/PDL1 trial aimed to treat patients with advanced or unresectable melanoma who were no longer responding to other drugs. The FDA granted breakthrough therapy designation based on data supported by Calyx’s central reviews which demonstrated preliminary clinical evidence that the drug potentially offered a substantial improvement over available therapies on the market.
The phase I study quickly became an advanced phase III study. Calyx supported a quick ramp-up, providing senior project management and industry-leading scientific guidance to help meet the demands of breakthrough therapy designation. This involved rapid modifications to the imaging charter and read design, adjusting from single review to double review with adjudication and clinical data evaluation by a central oncologist.
Calyx immediately expanded its reader pool and contracted nine additional radiologists and oncologists with expertise in melanoma imaging to meet the sponsor’s expedited review timelines and increased read volume.
Calyx’s medical imaging expertise and access to a deep network of experienced independent readers proved to be a key contributor to the success of the trial and to the FDA’s accelerated approval of the novel melanoma treatment.
Case Study: Meeting FDA Request for Expanded Imaging During RCC Compound Development
Calyx supported a phase III Renal Cell Carcinoma adjuvant therapy trial with approximately 1,000 enrolled patients. The trial began with an audit methodology reading only 20% of subjects and later, after receiving FDA feedback, expanded to a full review of all subjects.
The sponsor was interested in obtaining the full set of data as quickly as possible. Calyx responded by adding eight experienced readers to the study’s reviewer pool and managed expedited review for all cases. The Calyx study team closely monitored reader performance as data was reviewed, ensuring alignment and consistency across a large reader pool to deliver data that demonstrated the compound’s efficacy.
The study was a success and based on the imaging data delivered by Calyx Medical Imaging, the compound became the first FDA-approved immunotherapy for the adjuvant treatment of this RCC patient population.
