AIRPanc: A phase 2, open-label, multicenter, randomized study evaluating neoadjuvant therapy targeting the adenosine immunosuppressive pathway in combination with immune checkpoint blockade and radiation therapy in patients with advanced pancreatic ductal adenocarcinoma who are candidates for surgical resection.

• DOI: 10.1200/jco.2024.42.3_suppl.tps714
• Publication Date: 2024-01-22T21:12:58Z
• Authors: Gulam Abbas Manji; Brian William Lab...; Jacob K. Jamison; Linda Wu; Shikun Wang; Ilenia Pellicciotta; Sarah Sta Ana; Naomi Sender; Isabelle Ross; Hope Cho; David Paul Horowitz; John A. Chabot
• Keywords: Immune checkpoint; Neoadjuvant Therapy

TPS714 Background: Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease for which immune checkpoint blockade (ICB) has not provided benefit, hypothesized to be due the presence of immunosuppressive tumor microenvironment (TME). Neoadjuvant multi-agent chemotherapy and stereotactic body radiation therapy (SBRT) may increase immunosuppression by elevating intratumoral levels adenosine, metabolite. Adenosine, produced from adenosine triphosphate enzymes CD39 CD73, binds 2a 2b receptors (A2aR A2bR) expressed on cells inhibits critical components antitumor response. Human PDAC expresses high strongly associated with worse progression-free survival. Preclinical investigation demonstrated CD73 A2aR inhibition enhances responses, including increasing activity ICB. The goal this study test pathway in combination ICB SBRT patients advanced who are candidates surgical resection after receiving neoadjuvant chemotherapy. Methods: This investigator-initiated, open-label, multicenter, phase 2 clinical trial will randomize borderline resectable or locally have completed 8 cycles mFOLFIRINOX eligible one three treatment arms: zimberelimab (anti-PD-1) alone (Arm A), plus quemliclustat (anti-CD73) B), etrumadenant (A2aR/A2bR inhibitor)(Arm C) a period 7 weeks prior undergoing resection. 40 Gy 5 fractions, totaling biologically effective dose (BED) 72 Gy, delivered concurrently all randomized starting week treatment. Part I comprise six-patient safety run-in dose-de-escalation design treated according Arm C plan subsequent enrollment 14 additional per arm (N=42) II. primary endpoint CD8+ T-cell infiltration at time surgery compared between arms A. Group sample sizes achieve least 80% power detect effect size 1.23 significance level (alpha) 0.05 using two-sided two-sample t-test adjustment comparisons. Secondary objectives include estimation median OS, 18-month survival rate, R0 profile CA 19-9 biomarker Exploratory studies interrogating performed specimens. was opened May 19 th , 2023. Clinical information: NCT06048484 .