Abstract 3577: A first assessment of CD8-PET/CT with 89Zr-Crefmirlimab as predictive biomarker for response to standard of care immunotherapy in patients with solid tumors

Abstract

Abstract Background: Elevated levels of CD8+ tumor-infiltrating lymphocytes are associated with response to immunotherapy (IoT)1 in many indications. While immunohistochemistry (IHC) has been the method of choice to evaluate CD8+ tumor infiltration level, the utility of the CD8-PET/CT imaging method offers an attractive non-invasive alternative to biopsies, with the potential to account for both intra-patient tumor heterogeneity and lesion-specific response. Methods: Using the data from ImaginAb’s phase II trial2, we predict response to standard of care (SOC) IoT in patients with advanced solid malignancies. Solely based on CD8-PET/CT scan data, the novel method scores each identifiable lesion by using its volume as measured in the CT data, and mean CD8-PET uptake values before and 4 to 6 weeks after treatment start. All lesion scores are aggregated to compute the patient score, to be subsequently compared to the best standard RECIST evaluation. This methodology was defined and developed using data from 14 patients, and later evaluated using the whole cohort of 40 patients. Results: Despite the multiplicity of indications and SOC IoT in the patient cohort, the computed scores significantly identify and stratify responders (Complete or Partial Response, mean score = -0.78, 10 subjects) from non-responders (Stable or Progressive Disease, mean score = 0.088, 25 subjects): two sample t-test value = 5.378, p-value = 1e-05. RECIST evaluations remain too preliminary to report for 4 subjects. Furthermore, CD8-PET outcomes are available much earlier (median 35 days, median best of RECIST 105 days), which may facilitate important therapy decisions. In addition, the discriminative power between the response groups is reduced when restricting the method to either of the infiltration or lesion size measurements. This result highlights the complementarity of the two measurements. Conclusions: CD8-PET offers new non-invasive opportunities in the early discrimination of responders and non-responders to IoT as well as visualization of the heterogeneity of tumor responses to IoT, supporting its use pre-IoT and early on IoT for adult solid tumors. Acknowledgement: All the data used in this study come from clinical study 2. These data were acquired and discussed within the frame of a pre-competitive collaboration between AstraZeneca, Takeda, Pfizer and imaginAb. We want to thank the respective parties for fruitful discussions which helped us refine our analysis methodology.