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1472 Assessing the correlation between CD8 cell PET Imaging with 89-Zr-Crefmirlimab Berdoxam and CD8 cell immunohistochemistry in patients with advanced cancer receiving immunotherapy
  1. Michael Postow1,
  2. Audrey Mauguen1,
  3. Michael Farwell2,
  4. Michael Gordon3,
  5. David Hays4,5,
  6. Jeffrey Wong5,
  7. Sumanta Pal5,
  8. Delphine Chen6,
  9. Gary Ulaner7,
  10. Jonathan McConathy8,
  11. Michael Graham9,
  12. Anthony Shields10,
  13. Annick Van Den Abbeele11,
  14. Marcus Butler12,
  15. Jacob Thomas13,
  16. Przemyslaw Twardowski14,
  17. Jayant Narang15,6,
  18. Aman Singh15,
  19. Agnish Dey15,
  20. Kevin Maresca16,
  21. Edmund Keliher16,
  22. Feng Liu16,
  23. Guillaume Potdevin17,
  24. Guenter Schmidt17,
  25. Michael Ferris18,
  26. William Le18,
  27. Ian Wilson18,
  28. Ron Korn19,
  29. Neeta Pandit-Taskar1 and
  30. Kim Margolin14
  1. 1Memorial Sloan Kettering Cancer Center, New York, NY, USA
  2. 2University of Pennsylvania, Philadelphia, PA, USA
  3. 3Honor Health, Scottsdale, AZ, USA
  4. 4CARTI, Little Rock, AR, USA
  5. 5City of Hope, Duarte, CA USA
  6. 6University of Washington, Seattle, WA, USA
  7. 7Hoag Hospital, Newport, CA, USA
  8. 8University of Alabama, Birmingham, AL, USA
  9. 9University of Iowa, Iowa City, IA, USA
  10. 10Karmanos Cancer Institute, Detroit, MI, USA
  11. 11Dana Farber Cancer Institute, Boston, MA, USA
  12. 12Princess Margaret Hospital, Ontario, Canada
  13. 13HOAG, Los Angeles, CA, USA
  14. 14St. John’s Cancer Institute, Santa Monica, CA, USA
  15. 15Takeda Pharmaceuticals, Cambridge, MA, USA
  16. 16Pfizer, Cambridge, MA, USA
  17. 17AstraZeneca, Munich, Germany
  18. 18Imaginab, Bracknell, UK
  19. 19Imaging Endpoints, Scottsdale, AZ, USA


Background CD8 T-cells (CD8s) mediate the effects of most cancer immunotherapies. CD8s are typically assessed by biopsy which is inherently limited by sample availability, intratumoral and intrapatient heterogeneity, and difficulty with repeated, longitudinal assessment. Non-invasive CD8 PET imaging with 89-Zr-Crefmirlimab Berdoxam (crefmirlimab) could circumvent these barriers and has previously demonstrated feasibility and safety.

Methods We conducted a Phase II, prospective multicenter study to test the correlation between crefmirlimab PET signal and CD8 cell quantity by immunohistochemistry (IHC) in patients with solid tumors receiving standard of care immunotherapy. Patients underwent a baseline CD8 PET scan within 1 week prior to starting immunotherapy. A second crefmirlimab PET scan was performed 4-6 weeks after starting immunotherapy. Pre-treatment tissue and a biopsy 4-6 weeks on-treatment were used for CD8 IHC assessment by SP-57 antibody stain. Bone biopsies and those with <5% tumor were excluded. The primary endpoint was the correlation between PET uptake in the biopsied tumors [SUVmax, SUVmean, SUVpeak; normalized to reference tissue] and CD8 IHC results [CD8 cells/mm2] using the Spearman’s correlation coefficient.

Results Among 52 enrolled patients with ≥1 crefmirlimab scan and corresponding biopsy, 48 patients had 35 baseline biopsies and 34 on-treatment biopsies evaluable for the primary endpoint. Eight solid tumor types were represented with renal cell carcinoma (RCC, n=21 samples), melanoma (n=23), and non-small cell lung cancer (NSCLC, n=17) being the most common. Among the examined imaging parameters, SUVmean of the biopsied tumor, normalized to Aorta (SUVmean/SUVaorta) provided the best correlation. For all 69 biopsied lesions, the SUVmean/SUVmean aorta correlated with CD8 cell density [cells per mm2] by IHC with a Spearman’s correlation coefficient of 0.58 (95% CI: 0.385 - 0.697). For the 35 baseline biopsies the correlation was 0.66 (95%CI: 0.387 - 0.825), and for the 34 on-treatment biopsies the correlation was 0.48 (95% CI: 0.148 - 0.713). The correlation for RCC, melanoma, and NSCLC was 0.77 (95% CI: 0.552 - 0.913), 0.55 (95% CI: 0.084 - 0.727), and 0.54 (95% CI: -0.121 - 0.774), respectively. The mean SUVmean lesion/SUVmean aorta and mean CD8 cell density were 1.71 (IQR: 0.93-1.55) and 509 (IQR:114-461) at baseline and 2.43 (IQR: 0.80-3.60) and 759 (IQR:158-963) post-treatment respectively.

Conclusions Non-invasive CD8 PET scanning with crefmirlimab correlates with CD8 assessment by IHC and permits whole patient, longitudinal CD8s assessment. Crefmirlimab imaging is under investigation as a biomarker for immunotherapy responsiveness in ongoing trials (NCT05013099) and could ultimately provide a useful tool for immunotherapy drug development and clinical management.

Trial Registration NCT03802123

Ethics Approval The study was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical

Practice (ICH-GCP) All patients provided written informed consent.

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