Informing patient stratification strategies for pivotal immunotherapy study of Metastatic Prostate Cancer 

A pharmaceutical company conducting a Phase II study of an immunotherapy drug for metastatic prostate cancer sought the support of Quibim to extract and analyze data from baseline imaging. Given that the drug being studied binds to prostate-specific membrane antigen (PSMA), it was hypothesized that its efficacy would correlate with PSMA expression, as found in studies of other PSMA-targeting compounds¹. 

The company wanted quantitative evidence to support the design of screening protocols for a subsequent pivotal study, aimed at improving the precision of patient stratification and refining eligibility criteria to optimize trial outcomes. 

Quibim devised a methodology to segment lesions of baseline PSMA PET/CT images, extract over one hundred features at a lesion and case level per patient, and correlate baseline imaging features with treatment response and disease progression measures such as PSA kinetics and time-to-progression (TTP)². For further information on this approach, please read our blog article From images to insights: Quantitative PSMA-PET coupled with AI in prostate cancer clinical trials.

This approach enables:

• Evaluating if PSMA PET is an appropriate imaging test for patient screening and stratification in a pivotal study.
• Determining what feature or combination of features can act as an imaging biomarker that accurately predicts response to the treatment, such as radiographic progression-free survival.³
• Identify thresholds bounding the inclusion criteria based on the imaging biomarker, striking a balance between criteria that are strict enough to ensure patient safety and study validity, but not so restrictive that they limit recruitment or make the study population unrepresentative.
• Defining an imaging biomarker based on regulatory-cleared imaging methods to support the generalizability of the study to a broader population seen in clinical practice.

References

1. E. Delpassand et al., “Preliminary efficacy and safety results from the TATCIST trial: A PSMA-directed targeted alpha therapy with FPI-2265 (225Ac-PSMA-I&T) for the treatment of metastatic castration-resistant prostate cancer” presented at AACR, San Diego (CA, USA), April 5-10, 2024, poster presentation, abstract CT224. [Online]. Available at: https://fusionpharma.com/wp-content/uploads/2024/04/AACR-2024-TATCIST-Study-Poster_040524_corrected.pdf  

2. S. Vizel, “From images to insights: Quantitative PSMA-PET coupled with AI in prostate cancer clinical trials”. Quibim (31 May 2024). [Online]. Available at:  https://quibim.com/news/from-images-to-insights-quantitative-psma-pet-coupled-with-ai-in-prostate-cancer-clinical-trialspsma/ 

3. deSouza, N.M., Achten, E., Alberich-Bayarri, A. et al. Validated imaging biomarkers as decision-making tools in clinical trials and routine practice: current status and recommendations from the EIBALL* subcommittee of the European Society of Radiology (ESR). Insights Imaging 10, 87 (2019). https://doi.org/10.1186/s13244-019-0764-0