The study addressed these challenges through its clinical trial design, integrated immune monitoring strategy, and advanced analytical and data management methodologies.
Longitudinal immune monitoring was implemented to assess in vivo persistence and activity of PRAME-specific TCR-engineered T cells. Quantitative PCR and flow cytometry were used at multiple post-infusion time points to evaluate T-cell persistence and explore correlations with tumour response.
Exploratory biomarker analyses, including cellular and soluble immune markers, were incorporated to support mechanistic understanding of treatment activity and variability in patient response.
Tumour responses were assessed using both RECIST 1.1 and immune-related RECIST (irRECIST), enabling capture of conventional and immune-mediated response patterns. Patient selection incorporated confirmation of PRAME expression through tumour biopsy-based testing to maximise the likelihood of observing biological and clinical activity.
A combination therapy cohort was included to explore potential enhancement of anti-tumour responses and to monitor safety through systematic adverse event reporting and tumour response assessment.
Manufacturing feasibility was addressed through a stringent GMP-compliant production process for autologous T-cell products. Cell yield, production success rates, and quality control checkpoints were evaluated to ensure consistent clinical-grade product quality.
To account for variability in patient responses and tumour heterogeneity, generalised linear mixed models (GLMMs) and propensity score weighting were employed to adjust for confounding variables and enable robust comparisons across treatment cohorts.
The study also required ongoing updates to the electronic data capture (EDC) system due to frequent protocol amendments. Quanticate implemented controlled database updates, validation, and quality assurance processes to maintain data integrity and regulatory compliance throughout the study lifecycle. This involved strategic thinking around how to migrate databases of existing subjects to new standards and how to analyse the data pooled from different CRF designs.
Due to many of the novel endpoints and data being captured, Quanticate had to give careful thought to how these results would be most correctly mapped within the CDISC data structure, to facilitate analysis, while also complying with regulatory requirements. Quanticate also deployed a number of self-developed SDTM mapping and creation tools to streamline the first parts of the CDISC data flow.
