Poster Presentation 35th Lorne Cancer Conference 2023

Initial biodistribution data of ImmunoPET a Phase 0/1 Study characterising PD-L1 with 89Zr- Durvalumab (MEDI4736) PET/CT (#159)

Fiona Hegi-Johnson 1 2 , Stacey E Rudd 3 , Christian W Wichmann 2 4 , Tim Akhurst 5 , Peter Roselt 5 , Jason Callahan 5 , Price Jackson 5 , Rod Hicks 6 7 , Andrew Scott 4 8 9 , Paul Donnelly 3 , Thomas John 2 10 , Gerard G Hanna 1 , Michael MacManus 1 2
  1. Department of Radiation Oncology , Peter MacCallum Cancer Centre, Melbourne
  2. Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne
  3. School of Chemistry and Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Melbourne
  4. Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine , La Trobe University, Melbourne
  5. Cancer Imaging, Peter MacCallum Cancer Centre, Melbourne
  6. Department of Medicine, St Vincent's Medical School, University of Medicine, Melbourne
  7. Department of Medicine, Central Medical School, The Alfred Hospital, Monash University, Melbourne
  8. Department of Molecular Imaging and Therapy, Austin Health, Melbourne
  9. University of Melbourne, Melbourne
  10. Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne

 Introduction

ImmunoPET is a multicentre, single arm, phase 0-1 study that uses  89Zr-durvalumab PET/CT to interrogate the expression of PD-L1 in NSCLC patients. We present the initial biodistribution data, which has been  used to establish the safety and scan timepoints for a multicentre study in Stage III NSCLC patients.

Methods

The Phase 0 study recruited 5 PD-L1+ patients with metastatic NSCLC and PD-L1 expression >25%. Patients received 60MBq/70kg 89Zr-durvalumab up to a maximum of 74 MBq, with scan acquisition at day 0, 1, 3 or 5 ± 1 day. Baseline FDG PET/CT was also performed 7 days prior to injection of 89Zr-durvalumab. We present data on 1) Percentage of injected 89Zr-durvalumab uptake found in organs of interest (%ID) 2) Absorbed organ uptake (µSv/MBq of administered 89Zr-durvalumab) and 3) Whole-body dose expressed as mSv/100MBq of administered dose.

 

Results

5 patients have been recruited to the Phase 0 study, with no significant toxicity observed after tracer injection. 89Zr-durvalumab uptake increases from Day 0 to 5 post-injection in accordance with the long half-life of durvalumab.

 No significant toxicity was observed after tracer injection.  One patient had a transient infusion reaction, developing tachypnoea that resolved within 1 hour after dexamethasone and antihistamines.

Normal biodistribution is characterized at 5 days by high levels of whole-body retention (mean 84%), low kidney dose 0.82 ±0.22 and 0.70 ±0.26 (Mean ± SD) %ID for right and left kidney respectively) and rapidly diminishing circulation in blood pool from Day 1 19.79 ± 3.5 (mean±SD) Suvmax to 8.31± 2.21 SUVmax att Day 5. A small diminishment in bone uptake from 10.97±1.21 to 9.60±1.60 (mean± SD) %ID was also observed over 5 days. Spleen uptake as measured by % ID increased slightly between rising from 2.22±0.27 (mean ± SD) on Day 1 to 2.94 ± 0.78 on Day 5.

Conclusion

Initial biodistribution data suggests that the optimal scan timepoint is Day 5. There is very favourable avidity in PD-L1 positive metastatic lesions in comparison to normal organs with minimal toxicity, supporting the further evaluation of this tracer in a planned, multicentre trial in Stage III NSCLC patients.