Noninvasive assessment of programmed-death ligand-1 (PD-L1) in esophagogastric (EG) cancer using <sup>18</sup>F-BMS-986229 PET.
Authors: Samuel Louis Cytryn, Neeta Pandit-Taskar, Steven Brad Maron, Ping Gu, Geoffrey Yuyat Ku, Joanne F. Chou, Marinela Capanu, Lara Feder, Steven Philemond, Serge K. Lyashchenko, Jason Stuart Lewis, Viktoriya Paroder, Heiko Schöder, Amitabh Srivastava, Laura H. Tang, Yelena Y. Janjigian
Journal: Journal of Clinical Oncology (2024)

409 Background: PD-1 inhibitors are now standard in advanced EG cancer, with approval often based on PD-L1 CPS. However, single site biopsies are inadequate due to disease heterogeneity, dynamic changes over time, and variability due to operator, choice of assay, and tumor content. Better methods of non-invasive, comprehensive PD-L1 evaluation are needed. Methods: This is a prospective, pilot PET study of the positron-emitting agent 18 F-BMS-986229, a macrocyclic peptide with high affinity for PD-L1. Patients were administered 18 F-BMS-986229 intravenously and underwent whole body PET/CT 60 minutes later. The primary endpoint was safety and feasibility. Results: Ten patients underwent PD-L1 PET imaging. All had adenocarcinoma, 70% had metastatic disease, 20% had locally advanced, unresectable tumors, and 10% had resectable tumors. 30% of patients received prior treatment, including 2 with a PD-1 inhibitor. Median PD-L1 CPS was 10 (IQR 5-20). No patients experienced an adverse event associated with 18 F-BMS-986229. Although PD-L1 CPS ≥1 was required for inclusion, 2 patients who had PD-L1 CPS ≥1 on initial biopsy, had a subsequent biopsy closer in time, but still prior to PD-L1 PET imaging, with PD-L1 CPS &lt;1. In 8 of 10 patients, the biopsy site was evaluable by PD-L1 PET imaging. 5 of the 6 biopsy sites that were PD-L1 CPS ≥1, were PD-L1 PET avid; both biopsy sites that were PD-L1 CPS &lt;1 were appropriately non-avid. In sum, 88% of patients had radiographic and pathologic concordance. The Spearman rank correlation coefficients (r s ) between PD-L1 CPS and PD-L1 PET visualization score (scored 1 to 5, defined by accumulation greater than adjacent background) was 0.64, and 0.61 between PD-L1 CPS and PD-L1 PET SUV. Patients with a higher PD-L1 PET visualization score had a higher PD-L1 CPS: those with a maximum visualization score of 5 (n=4), had a median PD-L1 CPS of 22.5 (range 5-70), those with a maximum score of 4 (n=2) had PD-L1 CPS of 5 and 20, and those without any avid lesions (score of 3 or lower) had a median PD-L1 CPS of 5 (range 0-10). 71% of patients with PD-L1 PET avid lesions, also had non-avid sites of disease, 80% of whom had a more than 2-fold difference in SUV between the most and least avid lesions. 7 patients had untreated, advanced disease, 6 of whom were treated with PD-1 inhibitors as frontline therapy. 3 had PD-L1 PET avid lesions: 2 achieved a complete response (CR), the third achieved a partial response (PR), and progression free survival (PFS) was 32, 28, and 22 months respectively. Among the 3 patients with non-avid PD-L1 PET imaging who received PD-1 inhibitors as frontline therapy, 1 achieved a CR, 1 achieved a PR, and 1 had progressive disease, with PFS of 14.5, 10, and 2 months, respectively. Conclusions: We report the first use of PD-L1 PET imaging in patients with EG cancer and demonstrate its potential use as a companion diagnostic tool to aid in identifying patients who may benefit from PD-1 therapy. Clinical trial information: NCT04161781 .