126P Evaluation of myeloid targeting agents, PY159 and PY314, in two dose expansion phase Ib trials in platinum-resistant ovarian cancer
Year: 2023
Type: article
Abstract: Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells facilitate a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an agonist antibody to TREM1 that reprograms immunosuppressive intratumoral myeloid cells and PY314, an antagonist antibody to TREM2 that depletes tumor associated macrophages, as a single agent and in combination with pembrolizumab in subjects with PROC. PY159 and PY314 were individually evaluated in patients with PROC. Subjects were treated with monotherapy (PY159 3 mg/kg or PY314 10 mg/kg), based on the recommended dose for expansion derived from the Phase 1a studies. At the time of first progression, subjects could continue study drug and crossover to combination therapy with pembrolizumab (200 mg) every 3 weeks at the discretion of the investigator. Disease assessment by RECIST 1.1 was performed every 6 weeks. 17 subjects were enrolled in the PY159 study (median age 67, range 22-77; median prior therapies 6, range 2-18) and 16 subjects in PY314 (median age 65.5, range 49-81; median prior therapies 4, range 2-18). 7 subjects in PY159 and 8 subjects in PY314 crossed over to combination therapy. Safety events included the following: TRAEs occurred in 9 (56.3%) subjects in PY314 and 15 (88.2%) in PY159. IRRs occurred in 3 (18.8%) subjects in PY314 and 6 (35.3%) in PY159. irAEs occurred in 1 (6.3%) subject in PY314 (diarrhea) and 13 (76.5%) in PY159 (arthralgias). SAEs occurred in 12 (75%) subjects in PY314 (all unrelated) and 6 (36.3%) in PY159 (1 related). The best radiographic response in PY159 was stable disease in 8/16 subjects (50%; median 16 weeks, range 9-33), and in PY314, it was stable disease in 8/16 subjects (50%; median 12 weeks, range 6-36). Median PFS was 2.76 months and 2.69 months in PY159 and PY314, respectively. There were no responses in the crossover arm. Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as a single agent and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.
Source: Immuno-Oncology Technology
Institutions: Harvard University, Massachusetts General Hospital, Mary Crowley Cancer Research Center, Mayo Clinic in Florida, Florida Cancer Specialists & Research Institute, South Texas Accelerated Research Therapeutics, Yale University, OU Health, OU Health Stephenson Cancer Center, University of Oklahoma Health Sciences Center, University Hospitals Cleveland Medical Center, The University of Texas MD Anderson Cancer Center, HonorHealth, Allina Health, Oregon Health & Science University, OHSU Knight Cancer Institute, University of Wisconsin Carbone Cancer Center, University of Colorado Anschutz, University of Colorado Denver, Wayne State University, The Barbara Ann Karmanos Cancer Institute
Language: English
Subfield: Reproductive Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,020
OpenAlex ID: W4389480811