Abstract CT246: Phase 1b/2 study of giloralimab in combination with modified FOLFIRINOX with or without budigalimab in patients with untreated metastatic pancreatic cancer
Authors: Le Dung T. , Cruz-Correa Marcia , Bajor David L. , Garcia-Carbonero Rocio , Harris Marion , Pazo-Cid Roberto , Kindler Hedy , Yee Nelson , Kamath Suneel , Patel Maulik , Fang Hua , Henner William , Hardesty Patrick , Blaney Martha , McDevitt Michael , Golan Talia 
Published: June 2022

Abstract
Background: The 5-year survival rate for metastatic pancreatic cancer is ~3%, indicating an urgent need for novel therapies. Combination therapy with modified FOLFIRINOX (leucovorin, irinotecan, 5-fluorouracil, and oxaliplatin) and immunotherapy has been proposed for first-line metastatic pancreatic cancer to improve tolerability and clinical efficacy, respectively (NCCN, Pancreatic. 2021; Vonderheide, Annu. Rev. Med. 2020). The present study evaluates the safety, pharmacokinetics, and preliminary antitumor activity of modified FOLFIRINOX + giloralimab (CD40 agonist) with or without budigalimab (anti-PD-1) in patients with untreated metastatic pancreatic cancer.
Methods: Multicenter, randomized phase 1b/2 study (NCT04807972) in patients (18-75 years) with untreated metastatic pancreatic cancer. The phase 1b (dose escalation) examines the safety dose level of giloralimab in a triplet of modified FOLFIRINOX + giloralimab + budigalimab using a Bayesian optimal interval [BOIN] design. BOIN design is utilized to guide giloralimab escalation decisions. In phase 2 (dose expansion), patients are randomized 1:1:1 to receive treatment with modified FOLFIRINOX (cohort A), modified FOLFIRINOX + giloralimab (cohort B), or modified FOLFIRINOX + giloralimab + budigalimab (cohort C). Randomization is stratified according to Eastern Cooperative Oncology Group performance status. Primary objectives are to assess the safety and tolerability of modified FOLFIRINOX + giloralimab + budigalimab (phase 1b) and to evaluate overall survival in patients treated with modified FOLFIRINOX + giloralimab with or without budigalimab (versus those receiving modified FOLFIRINOX alone; phase 2). Secondary objectives include characterizing the pharmacokinetics of giloralimab and budigalimab in combination with modified FOLFIRINOX, assessing the efficacy of modified FOLFIRINOX + giloralimab with or without budigalimab, and evaluating the safety/tolerability of modified FOLFIRINOX + giloralimab with or without budigalimab. Patients will receive giloralimab and budigalimab intravenously in combination with modified FOLFIRINOX in a 28-day cycle. Dose-limiting toxicities are assessed during the first cycle of dosing. Adverse events are evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events. Blood samples for pharmacokinetic analysis are collected at designated time points throughout the study. Responses are assessed by Response Evaluation Criteria in Solid Tumors version 1.1. Survival outcomes are described using the Kaplan-Meier method. Approximately 129 patients are planned to be included. Enrollment started in June 2021, with 7 patients enrolled as of November 2021.
Citation Format: Dung T. Le, Marcia Cruz-Correa, David L. Bajor, Rocio Garcia-Carbonero, Marion Harris, Roberto Pazo-Cid, Hedy Kindler, Nelson Yee, Suneel Kamath, Maulik Patel, Hua Fang, William Henner, Patrick Hardesty, Martha Blaney, Michael McDevitt, Talia Golan. Phase 1b/2 study of giloralimab in combination with modified FOLFIRINOX with or without budigalimab in patients with untreated metastatic pancreatic cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr CT246.