Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer
Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote a hostile tumor microenvironment and are associated with worse clinical outcomes in PROC. We evaluated the safety and preliminary efficacy of PY159, an...
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BMJ Publishing Group
2025-03-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/13/3/e010959.full |
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| author | Afshin Dowlati Judy Wang Siqing Fu Amita Patnaik Minal Barve Shivaani Kummar Abdul Rafeh Naqash Patricia LoRusso Michael Gordon Debra L Richardson Ira Winer Christos Kyriakopoulos Joleen Hubbard Marc Chamberlain Oladapo O Yeku Winston W Tan Sarah K Lynam |
| author_facet | Afshin Dowlati Judy Wang Siqing Fu Amita Patnaik Minal Barve Shivaani Kummar Abdul Rafeh Naqash Patricia LoRusso Michael Gordon Debra L Richardson Ira Winer Christos Kyriakopoulos Joleen Hubbard Marc Chamberlain Oladapo O Yeku Winston W Tan Sarah K Lynam |
| author_sort | Afshin Dowlati |
| collection | DOAJ |
| description | Background Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote 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 Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral myeloid cells, and PY314, an antagonist antibody to Triggering receptor expressed on myeloid cells-2 (TREM2) that depletes tumor-associated macrophages, as single agents and in combination with pembrolizumab in subjects with PROC.Methods PY159 and PY314 were individually evaluated in patients with PROC. Patients 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, patients 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 Response Evaluation Criteria in Solid Tumor version 1.1 was performed every 6 weeks.Results 17 patients were enrolled in the PY159 study (median age 67, range 22–77; median prior therapies 6, range 2–18) and 16 patients in PY314 (median age 65.5, range 49–81; median prior therapies 4, range 2–10). 7 patients in PY159 and 8 patients in PY314 crossed over to combination therapy. Safety events included the following: treatment-related adverse events occurred in 15 patients (88.2%) in PY159 and 9 patients (56.3%) in PY314. Infusion-related reactions occurred in 6 patients (35.3%) in PY159 and 3 patients (18.8%) in PY314. Immune-related adverse events occurred in 13 patients (76.5%) in PY159 (arthralgias) and 1 patient (6.3%) in PY314 (diarrhea). Serious adverse events occurred in 6 patients (36.3%) in PY159 (1 related) and 12 patients (75%) in PY314 (all unrelated). The best radiographic response in PY159 was stable disease in 8/16 patients (50%; median 16 weeks, range 9–33), and in PY314, it was stable disease in 8/16 patients (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.Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC. |
| format | Article |
| id | doaj-art-af3f85e946a04081b09dd7efa3dc1253 |
| institution | DOAJ |
| issn | 2051-1426 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMJ Publishing Group |
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| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-af3f85e946a04081b09dd7efa3dc12532025-08-20T02:42:59ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262025-03-0113310.1136/jitc-2024-010959Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancerAfshin Dowlati0Judy Wang1Siqing Fu2Amita Patnaik3Minal Barve4Shivaani Kummar5Abdul Rafeh Naqash6Patricia LoRusso7Michael Gordon8Debra L Richardson9Ira Winer10Christos Kyriakopoulos11Joleen Hubbard12Marc Chamberlain13Oladapo O Yeku14Winston W Tan15Sarah K Lynam163University Hospitals Cleveland Medical Center, Cleveland, OH, USA1 Vascular Surgery, Northern Hospital, Epping, Victoria, AustraliaInvestigational Cancer Therapeutics, University of Texas MD Anderson Cancer Center, Houston, Texas, USA4The START Center for Cancer Research, San Antonio, TX, USA7Mary Crowley Cancer Research, Dallas, TX, USA6Oregon Health and Science University, Portland, OR, USA9 Medical Oncology/TSET Phase 1 Program, Stephenson Cancer Center/Sarah Cannon Research Institute, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USAYale University School of Medicine, New Haven, Connecticut, USAHonorHealth Research Institute, Scottsdale, Arizona, USA7Stephenson Cancer Centre-University of Oklahoma, Oklahoma City, OK4Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MIUniversity of Wisconsin-Madison, Madison, WI, USA8 Department of Oncology, Mayo Clinic, Rochester, Minnesota, USAPionyr Immunotherapeutics, South San Francisco, CA, USA1 Medicine/Cancer Center, Massachusetts General Hospital, Boston, Massachusetts, USA3 Mayo Clinic, Jackson, Florida, USA10 University Hospitals Seidman Cancer Center and Case Western Reserve University, Cleveland, Ohio, USABackground Novel treatment options are required in patients with platinum-resistant ovarian cancer (PROC). Myeloid-derived suppressor cells promote 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 Triggering receptor expressed on myeloid cells-1 (TREM1) that reprograms immunosuppressive intratumoral myeloid cells, and PY314, an antagonist antibody to Triggering receptor expressed on myeloid cells-2 (TREM2) that depletes tumor-associated macrophages, as single agents and in combination with pembrolizumab in subjects with PROC.Methods PY159 and PY314 were individually evaluated in patients with PROC. Patients 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, patients 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 Response Evaluation Criteria in Solid Tumor version 1.1 was performed every 6 weeks.Results 17 patients were enrolled in the PY159 study (median age 67, range 22–77; median prior therapies 6, range 2–18) and 16 patients in PY314 (median age 65.5, range 49–81; median prior therapies 4, range 2–10). 7 patients in PY159 and 8 patients in PY314 crossed over to combination therapy. Safety events included the following: treatment-related adverse events occurred in 15 patients (88.2%) in PY159 and 9 patients (56.3%) in PY314. Infusion-related reactions occurred in 6 patients (35.3%) in PY159 and 3 patients (18.8%) in PY314. Immune-related adverse events occurred in 13 patients (76.5%) in PY159 (arthralgias) and 1 patient (6.3%) in PY314 (diarrhea). Serious adverse events occurred in 6 patients (36.3%) in PY159 (1 related) and 12 patients (75%) in PY314 (all unrelated). The best radiographic response in PY159 was stable disease in 8/16 patients (50%; median 16 weeks, range 9–33), and in PY314, it was stable disease in 8/16 patients (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.Conclusions Both PY159 and PY314 were well tolerated, with an acceptable safety profile, as both single agents and in combination with pembrolizumab. Both agents warrant further investigation in heavily pretreated PROC.https://jitc.bmj.com/content/13/3/e010959.full |
| spellingShingle | Afshin Dowlati Judy Wang Siqing Fu Amita Patnaik Minal Barve Shivaani Kummar Abdul Rafeh Naqash Patricia LoRusso Michael Gordon Debra L Richardson Ira Winer Christos Kyriakopoulos Joleen Hubbard Marc Chamberlain Oladapo O Yeku Winston W Tan Sarah K Lynam Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer Journal for ImmunoTherapy of Cancer |
| title | Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer |
| title_full | Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer |
| title_fullStr | Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer |
| title_full_unstemmed | Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer |
| title_short | Myeloid targeting antibodies PY159 and PY314 for platinum-resistant ovarian cancer |
| title_sort | myeloid targeting antibodies py159 and py314 for platinum resistant ovarian cancer |
| url | https://jitc.bmj.com/content/13/3/e010959.full |
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