Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer
This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to re...
Saved in:
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2024-12-01
|
| Series: | Human Vaccines & Immunotherapeutics |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/21645515.2024.2379864 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850185188067246080 |
|---|---|
| author | Charles L. Wiseman Jarrod P. Holmes Carmen Calfa Shaker R. Dakhil Saveri Bhattacharya George E. Peoples Markus D. Lacher Miguel Lopez-Lago Alex Kharazi Giuseppe Del Priore Mingjin Chang Daniel L. Adams William V. Williams |
| author_facet | Charles L. Wiseman Jarrod P. Holmes Carmen Calfa Shaker R. Dakhil Saveri Bhattacharya George E. Peoples Markus D. Lacher Miguel Lopez-Lago Alex Kharazi Giuseppe Del Priore Mingjin Chang Daniel L. Adams William V. Williams |
| author_sort | Charles L. Wiseman |
| collection | DOAJ |
| description | This Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), with pre-dose low-dose cyclophosphamide and post-dose local interferon alpha. Twenty-six patients were enrolled; 23 (88.5%) were inoculated, receiving a total of 79 inoculations. There were six Grade 4 and one Grade 5 adverse events noted (judged unrelated to SV-BR-1-GM). Disease control (stable disease [SD]) occurred in 8 of 16 evaluable patients; 4 showed objective regression of metastases, including 1 patient with near-complete regressions in 20 of 20 pulmonary lesions. All patients with regressions had human leukocyte antigen (HLA) matches with SV-BR-1-GM; non-responders were equally divided between matching and nonmatching (p = .01, Chi-squared), and having ≥2 HLA matches with SV-BR-1-GM (n = 6) correlated with clinical benefit. Delayed-type hypersensitivity (DTH) testing to candida antigen and SV-BR-1-GM generated positive responses (≥5 mm) in 11 (42.3%) and 13 (50%) patients, respectively. Quantifying peripheral circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) showed that a drop in CAMLs was significantly correlated with an improvement in progression-free survival (PFS; 4.1 months vs. 1.8 months, p = .0058). Eight of 10 patients significantly upregulated programmed cell death ligand 1 (PD-L1) on CTCs/CAMLs with treatment (p = .0012). These observations support the safety of the Bria-IMT regimen, demonstrate clinical regressions, imply a role for HLA matching, and identify a possible value for monitoring CAMLs in peripheral blood. |
| format | Article |
| id | doaj-art-67922cae6ff54870900ebf2a5b42091c |
| institution | OA Journals |
| issn | 2164-5515 2164-554X |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Human Vaccines & Immunotherapeutics |
| spelling | doaj-art-67922cae6ff54870900ebf2a5b42091c2025-08-20T02:16:49ZengTaylor & Francis GroupHuman Vaccines & Immunotherapeutics2164-55152164-554X2024-12-0120110.1080/21645515.2024.2379864Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancerCharles L. Wiseman0Jarrod P. Holmes1Carmen Calfa2Shaker R. Dakhil3Saveri Bhattacharya4George E. Peoples5Markus D. Lacher6Miguel Lopez-Lago7Alex Kharazi8Giuseppe Del Priore9Mingjin Chang10Daniel L. Adams11William V. Williams12Development, BriaCell Therapeutics Corp, Philadelphia, PA, USAHematology Oncology, Providence Medical Group Santa Rosa - Cancer Center, Santa Rosa, CA, USAMedical Oncology, University of Miami, Miami, FL, USAMedical Oncology, Cancer Center of Kansas, Wichita, KS, USAAbramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USAOncology, Lumabridge, San Antonio, TX, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USADiscovery, Creatv MicroTech, Inc., Rockville, MD, USADevelopment, BriaCell Therapeutics Corp, Philadelphia, PA, USAThis Phase I/IIa open-label, single-arm clinical trial addressing advanced, refractory, metastatic breast cancer was conducted at six medical centers in the United States. We repeated inoculations with irradiated SV-BR-1-GM, a breast cancer cell line with antigen-presenting activity engineered to release granulocyte-macrophage colony-stimulating factor (GM-CSF), with pre-dose low-dose cyclophosphamide and post-dose local interferon alpha. Twenty-six patients were enrolled; 23 (88.5%) were inoculated, receiving a total of 79 inoculations. There were six Grade 4 and one Grade 5 adverse events noted (judged unrelated to SV-BR-1-GM). Disease control (stable disease [SD]) occurred in 8 of 16 evaluable patients; 4 showed objective regression of metastases, including 1 patient with near-complete regressions in 20 of 20 pulmonary lesions. All patients with regressions had human leukocyte antigen (HLA) matches with SV-BR-1-GM; non-responders were equally divided between matching and nonmatching (p = .01, Chi-squared), and having ≥2 HLA matches with SV-BR-1-GM (n = 6) correlated with clinical benefit. Delayed-type hypersensitivity (DTH) testing to candida antigen and SV-BR-1-GM generated positive responses (≥5 mm) in 11 (42.3%) and 13 (50%) patients, respectively. Quantifying peripheral circulating tumor cells (CTCs) and cancer-associated macrophage-like cells (CAMLs) showed that a drop in CAMLs was significantly correlated with an improvement in progression-free survival (PFS; 4.1 months vs. 1.8 months, p = .0058). Eight of 10 patients significantly upregulated programmed cell death ligand 1 (PD-L1) on CTCs/CAMLs with treatment (p = .0012). These observations support the safety of the Bria-IMT regimen, demonstrate clinical regressions, imply a role for HLA matching, and identify a possible value for monitoring CAMLs in peripheral blood.https://www.tandfonline.com/doi/10.1080/21645515.2024.2379864SV-BR-1-GMbreast cancerimmunotherapytherapeutic cancer vaccinehistocompatibility markersTrial registration |
| spellingShingle | Charles L. Wiseman Jarrod P. Holmes Carmen Calfa Shaker R. Dakhil Saveri Bhattacharya George E. Peoples Markus D. Lacher Miguel Lopez-Lago Alex Kharazi Giuseppe Del Priore Mingjin Chang Daniel L. Adams William V. Williams Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer Human Vaccines & Immunotherapeutics SV-BR-1-GM breast cancer immunotherapy therapeutic cancer vaccine histocompatibility markers Trial registration |
| title | Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer |
| title_full | Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer |
| title_fullStr | Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer |
| title_full_unstemmed | Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer |
| title_short | Results of a phase I/IIa trial of SV-BR-1-GM inoculation with low-dose cyclophosphamide and interferon alpha (Bria-IMT) in metastatic breast cancer |
| title_sort | results of a phase i iia trial of sv br 1 gm inoculation with low dose cyclophosphamide and interferon alpha bria imt in metastatic breast cancer |
| topic | SV-BR-1-GM breast cancer immunotherapy therapeutic cancer vaccine histocompatibility markers Trial registration |
| url | https://www.tandfonline.com/doi/10.1080/21645515.2024.2379864 |
| work_keys_str_mv | AT charleslwiseman resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT jarrodpholmes resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT carmencalfa resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT shakerrdakhil resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT saveribhattacharya resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT georgeepeoples resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT markusdlacher resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT miguellopezlago resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT alexkharazi resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT giuseppedelpriore resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT mingjinchang resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT danielladams resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer AT williamvwilliams resultsofaphaseiiiatrialofsvbr1gminoculationwithlowdosecyclophosphamideandinterferonalphabriaimtinmetastaticbreastcancer |