Circulating tumor cell (CTC) PD-L1 and interferon regulatory factor-1 (IRF-1) expression as biomarkers of anti-PD-(L)1 response.

person Laura Kennedy University of Washington, Seattle, WA info_outline Laura Kennedy, Arturo B. Ramirez, Lance U'Ren, Yao Sun, Grace Durenberger, Laura Quan Man Chow, Petros Grivas, Vijayakrishna K. Gadi

Authors person Laura Kennedy University of Washington, Seattle, WA info_outline Laura Kennedy, Arturo B. Ramirez, Lance U'Ren, Yao Sun, Grace Durenberger, Laura Quan Man Chow, Petros Grivas, Vijayakrishna K. Gadi Organizations University of Washington, Seattle, WA, RareCyte, Inc., Seattle, WA, Rarecyte, Inc., Seattle, WA, Fred Hutchinson Cancer Research Institute, Seattle, WA, Division of Medical Oncology, University of Washington, Seattle, WA, University of Washington, School of Medicine, Seattle, WA Abstract Disclosures Research Funding Other Background: Anti-PD-(L)1 checkpoint inhibitors (CPI) are remarkable due to durable responses, tolerability, and improvements in survival across multiple solid tumors. Unfortunately, CPI produce objective responses in only a small subset of solid tumors patients (pts). We hypothesized that PD-L1 and IRF-1 expression on CTC may correlate with CPI response, and evaluate their expression in this pilot study. Methods: Pts with metastatic solid tumors initiating anti-PD(L)-1 mono- or combination therapy were eligible. Pts had 7.5 cc of blood drawn for CTC evaluation at 3 timepoints: baseline, after 1 CPI dose, and 3-6 months after starting CPI or at time of CPI discontinuation. Peripheral blood CTC were isolated with the AccuCyte kit and stained for CK/EpCAM, anti-CD45, nuclear dye, PD-L1, and IRF-1. CTCs were then identified with CyteFinder software. Results: 16 pts have enrolled to date with median age 71 years (range 28-83) and median ECOG = 1 (range 0-3). 50% were female. Diagnoses include NSCLC (50%), head and neck cancer (13%), breast cancer (13%), and others (24%). CTC were identified at baseline in 13/16 pts (# CTCs range 0-101). 12 pts with baseline CTC have had restaging scans since starting CPI. By RECIST 1.1, 3 pts had partial response (PR), 1 had stable disease (SD), and 8 had progressive disease (PD). The pts with PR more frequently had IRF-1 staining on baseline CTC (Table), and 1/3 had PD-L1 staining. 6 pts had tumor PD-L1 staining available for correlation, and 3/6 of those pts were PD-L1+ (tissue PD-L1 ≥ 1%). 1/3 pts with PD-L1+ tumor staining had CTCs that were PD-L1+. In the 3 pts with negative PD-L1 tumor staining, 1 pt had a mixed PD-L1+/PD-L1- CTC population and the others had no PD-L1 staining. Conclusions: CTC isolation and enumeration seem feasible across tumor types. Pts with PR to anti-PD-(L)1/ might have higher prevalence of IRF-1+ CTC; however, results are preliminary and more pts and samples are being evaluated. PD-L1/IRF-1+ CTC by treatment response. Best CPI Response #Pts CTC Count Range # Pts with PD-L1 + CTC (Prevalence of +CTC / Pt) # Pts with IRF-1+ CTC (Prevalance of +CTC / Pt) PR 3 1-2 1/3 (0-100%) 2/3 (0-100%) SD 1 3-3 0/1 (0-0%) 0/1 (0-0%) PD 8 1-101 4/8 (3-25%) 3/8 (4-60%)