Whole body PD-1 and PD-L1 PET with ⁸⁹Zr-nivolumab and ¹⁸F- BMS-986192 in pts with NSCLC.

e20047 Background: Tumor PD-L1 IHC relates moderately with treatment outcome following anti-PD-(L)1 monotherapy in pts with NSCLC. Aim: 1. To assess safety of the PET procedures. 2. To quantify PD-1 and PD-L1 expression in tumors with 89Zirconium-labeled nivolumab (89Zr-nivo) and 18F-labeled BMS-986192 (18F-PD-L1) PET. 3. To assess intra- and inter-patient tracer uptake differences in tumors. 4. To correlate PET results with IHC and treatment outcome. Methods: NSCLC pts eligible for treatment with nivolumab were included. Pts received a dynamic and static whole body 18F-PD-L1 and a static 89Zr-nivo PET scan. A baseline tumor biopsy was required and up to two additional biopsies were allowed in case PET showed heterogeneous tumor uptake. SUVpeak was calculated for all delineable tumor lesions and related to PD-(L)1 IHC (28.8 assay) and response after 6 wks of nivolumab treatment. Results: 7 pts (5 ≥1%, 2 ≥50% and 2 negative by PD-L1 IHC) were enrolled and 11 lesions analyzed. No toxicity related to radiotracer administration was identified. Tumor uptake of both tracers was visualized in all pts. There was substantial variability among pts for 18F-PD-L1 (mean SUV 5.4, range 2.2 - 14.4) and 89Zr-nivo (mean SUV 5.0, range 1.6 - 9.7). Intra-patient tracer uptake heterogeneity was also seen: mean 2.5-fold (±0.96) and 2.3-fold (±0.86) differences between lesions for 18F-PD-L1 and 89Zr-nivo SUV, respectively. For lesions with < 50% PD-L1 IHC mean 18F-PD-L1 SUV was 3.4 (±2.9) as compared to 7.1 (±6.0) for lesions with ≥50% PD-L1 IHC (p = 0.22). For lesions with low PD-1 expression mean 89Zr-nivo SUV was 6.9 (±2.7) as compared to 8.1 (±2.0) for lesions with high PD-1 expression (p = 0.44). Five pts were evaluable for response evaluation: 1 PR, 2 SD and 2 PD with 18F-PD-L1 SUV values (most PET avid lesion) of 14.4 (PR), 2.0 and 5.4 (SD) and 6.4 and 6.6 (PD). Conclusion: 1.PET-imaging with both tracers is safe and feasible, with good tumor-to-normal tissue contrast. 2. Tumor uptake demonstrated substantial heterogeneity among pts and among tumors within the same pts. 3. Although higher 18F-PD-L1 tumor uptake was seen in pts with ≥50% tumor PD-L1 IHC and the highest 18F-PD-L1 SUV was measured in the responding pt, the dataset is still very small. Clinical trial information: 2015-004760-11.