.png){kind=icon}
.png){kind=icon}
Return
A phase I/II trial of avelumab combinations with ivuxolimab, utomilumab, and radiation therapy in patients with advanced gastrointestinal malignancies
.png){kind=icon}
PRE
AI
DOI：10.1093/oncolo/oyaf032.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Background Checkpoint agonists utomilumab (4-1BB agonist) and ivuxolimab (OX40 agonist) enhance Teffector cell function. Preclinical studies suggest that combining these drugs with avelumab (anti-PD-L1 antibody) can potentially synergize this effect. In addition, tissue abscopal effects of radiation therapy may improve antigen presentation, complementing PD-L1 blockade. We conducted a single institution, open-label, multi-arm, non-randomized, phase 1/2 clinical trial of avelumab in combination with ivuxolimab, with or without utomilumab, and radiation therapy in patients with advanced solid tumors. Herein, we present a subgroup analysis in patients with gastrointestinal (GI) tumors (pancreatic, colon, gastric, and hepatocellular).Methods The primary objectives of this study were to assess safety, tolerability, and dose-limiting toxicities. The secondary objectives were to evaluate efficacy including response rate, progression free survival (PFS), as determined by immune-related Response Criteria in Solid Tumors (irRECIST) and overall survival (OS).Results Thirty-one patients with pancreatic (n = 21), colorectal (n = 8), hepatocellular (n = 1), and gastric (n = 1) cancers were included in this study. The most common treatment-related adverse events (TRAEs) were chills (13%), diarrhea (10%), colitis (10%), fatigue (6%), and fever (6%). There were 3 instances of grade 3 diarrhea and colitis (10%) without any other grade >= 3 TRAEs Among the 24 patients evaluable for response, 9 (37.5%) had immune-related stable disease (irSD) and 14 (58.3%) had immune-related progressive disease (irPD). One patient had clinical progression without radiological confirmation. The median PFS was 2 months. Median OS was 5.6 months.Conclusion Combining avelumab with co-stimulatory checkpoint agonists produces modest activity without added safety concerns in patients with advanced GI malignancies (ClinicalTrials.gov Identifier: NCT03217747).
Keywords:
avelumab
ivuxolimab
utomilumab
PD-L1
OX40
4-IBB
immunotherapy
pancreatic
gastric
liver
colorectal
Journal
IF:
4.2
Papers:
642
Citations:
1.8W