CD8 cell PET imaging with 89-Zr-crefmirlimab berdoxam (crefmirlimab) in patients with metastatic renal cell carcinoma (mRCC) receiving checkpoint inhibitors (CPIs): Association with response and tissue CD8 expression.

4551 Background: Novel imaging modalities using frequently expressed RCC antigens, such as CAIX, have shown promise in early-stage disease (Shuch B et al ASCO GU 2023). In advanced RCC, no tissue-based biomarkers have been well established to predict outcome with contemporary regimens, e.g., checkpoint inhibitors (CPIs) or targeted therapy (TT). We hypothesize that functional imaging of CD8 T-cells (CD8s) with crefmirlimab (a ~80 kDA 89 Zr-labelled minibody with high affinity for CD8) may predict response given the essential role of CD8 T-cells (CD8s) in mediating CPI response. Methods: Eligible pts had pathologically verified RCC, metastatic disease and an intent to initiate standard of care CPI therapy. Patients received crefmirlimab PET/CT within 1 wk of CPI infusion and 4-6 weeks after initiating therapy. Baseline biopsy was mandated, along with repeat biopsy 0-2 weeks following the second PET/CT scan. PET signal was characterized as SUV max , SUV peak and SUV mean of the biopsied lesions, up to 5 index lesions and representative CD8 avid lymph nodes. Mean SUV max in responders and non-responders were compared using students t-test (1-sided). CD8 expression in tissue was characterized as the number of positive cells per mm 2 ; PET avidity and CD8 expression were compared using the Spearman correlation coefficient. Results: 17 pts (9 M: 8 F) were enrolled; most pts had clear cell histology (12; 71%) followed by unclassified (3; 17%) and papillary (2; 12%). The most commonly rendered CPI-based regimens were nivolumab alone (6 pts; 35%) and cabozantinib/nivolumab (3 pts; 17%). Follow-up data was available in 15 of the patients. By RECIST v1.1, 3 of 15 patients were classified as responders (best overall response [BOR] of complete response or partial response) and 12 patients were classified as non-responders (BOR of stable disease or progressive disease). Average SUV max , SUV peak and SUV mean per patient among all quantified index lesions and representative lymph nodes were 10.02, 6.95 and 6.11 for baseline and 8.82, 6.23 and 5.39 during treatment, respectively. Average SUV max at baseline was 14.68 in responders to CPI and 8.28 in non-responders (P=0.006). On treatment SUV max was 10.93 in responders to CPI and 8.22 in non-responders (P=0.19). A strong correlation between CD8 expression in baseline tissue and normalized SUV mean was observed (r=0.77; 95%CI 0.53-0.91). Conclusions: To our knowledge, this is the first series in RCC to demonstrate that functional imaging of immune cells (here, CD8s) may segregate response to CPIs, with responders having a higher baseline SUV and a larger decrement in SUV with therapy. Our results are bolstered by a significant correlation between tissue and imaging CD8 expression. Larger studies are underway to validate this noninvasive strategy. Clinical trial information: NCT03802123 .