Abstract 5611: LAG-3 PET imaging in patients with cancer before immune checkpoint inhibitor therapy
Authors: van de Donk Pim P. , Smit Lotte M. , van Sluis Joyce , Timens Wim , Brouwers Adrienne H. , de Hooge Marjolijn N. Lub- , Elias Sjoerd G. , Gietema Jourik A. , van Winkel Claudia A. , Wang JuAn , Giurleo Jason , Uldrick Thomas , Cheung Hung Kam , Jalving Hilde , Oosting Sjoukje F. , Knapen Daan G. , de Groot Derk-Jan A. , de Vries Elisabeth G. 
Published: April 2023

Background Immune checkpoint inhibitors (ICIs) can induce durable responses in multiple different tumor types. Lymphocyte activation gene-3 (LAG-3) is one of the immune checkpoints for which therapeutic antibodies are being developed. PET imaging with radiolabeled ICIs can visualize whether the drug reaches the tumor, and might serve as a target expression readout. Therefore, we aimed to evaluate the safety of the radiolabeled LAG-3 antibody 89Zr-DFO-REGN3767, to determine the optimal tracer dose and imaging time point, and to get insight into 89Zr-DFO-REGN3767 whole body distribution.

Methods Patients with advanced solid tumors received 37 MBq 89Zr-DFO-REGN3767 together with unlabeled antibody to achieve a 2, 5, 10, 20, or 40 mg total protein dose (NCT04706715). Patients underwent PET/CT scans on days 0, 2, 4, and 7 after injection, followed by a tumor biopsy. After that, they received treatment with cemiplimab alone or combined with platinum-containing chemotherapy. PET scans were analyzed by placing volumes of interest (VOIs) in tumor lesions and normal tissues. Tracer uptake was measured in the VOIs and expressed as the maximum standardized uptake value (SUVmax) for tumor lesions and as the mean standardized uptake value (SUVmean) for normal tissues.

Results The 16 included patients experienced no 89Zr-DFO-REGN3767-related side effects. Tumor-to-blood ratios for all dose levels increased from days 0 to 7. Therefore, imaging 7 days after tracer injection was deemed optimal to achieve the highest contrast. The 40 mg tracer dose resulted in the most favorable blood kinetics. At this dose, tracer uptake in tumor lesions (n = 17) varied between patients (geometric mean SUVmax 6.2; SD 1.7). In normal tissues, uptake was seen in the spleen (x̄ 11.2; SD 1.6), and bone marrow (x̄ 2.2; SD 0.7), which increased from days 0 to 7. Tracer uptake was visually present in regions with inflammation.

Conclusion 89Zr-DFO-REGN3767 PET imaging is feasible and studied patients did not experience tracer related side effects. Optimal imaging results were achieved with the 40 mg protein dose and imaging on day 7 89Zr-DFO-REGN3767 shows specific accumulation in LAG-3 rich tissues and tumor lesions.

Citation Format: Pim P. van de Donk, Lotte M. Smit, Joyce van Sluis, Wim Timens, Adrienne H. Brouwers, Marjolijn N. Lub- de Hooge, Sjoerd G. Elias, Jourik A. Gietema, Claudia A. van Winkel, JuAn Wang, Jason Giurleo, Thomas Uldrick, Hung Kam Cheung, Hilde Jalving, Sjoukje F. Oosting, Daan G. Knapen, Derk-Jan A. de Groot, Elisabeth G. de Vries. LAG-3 PET imaging in patients with cancer before immune checkpoint inhibitor therapy. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 5611.