CD8 PET imaging with 89 ZrZr-berdoxam-crefmirlimab in patients with solid tumors: the Phase II iCorrelate study

Background CD8 T cells mediate the effects of cancer immunotherapies. CD8 positron emission tomography (PET) imaging with 89 ZrZr-berdoxam-crefmirlimab enables whole body CD8 cell assessment and has been shown to be safe in Phase I evaluation. The correlation between CD8 PET imaging parameters and the quantity of CD8 cells assessed by the gold standard of immunohistochemistry (IHC) is unknown. Methods The Phase II, prospective multicenter study (iCorrelate) tested the correlation between CD8 PET and CD8 cells by IHC of core needle biopsies from patients with solid tumors receiving immune checkpoint blockade. The safety of repeat CD8 PET was additionally analyzed. Results 49 patients had 70 biopsies (37 baseline and 33 on-treatment) for correlating CD8 PET with IHC. Standard uptake value mean of the biopsied tumor normalized to aorta showed a correlation with IHC of 0.49 (95% CI 0.26 to 0.59). The correlation was 0.71 (95% CI 0.48 to 0.85) in patients with renal cell carcinoma. Repeat CD8 PET imaging on-treatment was safe. Conclusions We found a modest correlation between CD8 PET with 89 ZrZr-berdoxam-crefmirlimab and intratumoral CD8 cell counts, likely because core needle biopsies do not fully represent the intratumoral heterogeneity of the CD8 cell distribution. Continued research is essential to evaluate in vivo CD8 PET signals, autoradiography, and CD8 T-cell presence by IHC in fully resected tumors. Further studies investigating the correlation between CD8 PET and immunotherapy outcomes are necessary to determine whether CD8 PET imaging could become a valuable tool for guiding immunotherapy development and informing clinical decision-making.