Abstract CT171: Safety and efficacy of a whole-cell targeted immunotherapy for breast cancer: Preliminary findings
Authors: Holmes Jarrod P. , Tan-Chiu Elizabeth , Wiseman Charles L. , Lacher Markus D. , Peoples George , Williams William V. 
Published: August 2018

Abstract
The purpose of this study is to evaluate the safety and preliminary efficacy of a targeted immunotherapy for breast cancer based on SV-BR-1-GM, a breast cancer cell line modified to secrete GM-CSF. The regimen used includes low dose cyclophosphamide (300 mg/m2) 2-3 days prior to inoculation to reduce immune suppression; irradiated SV-BR-1-GM (20,000 cGy) dosed intradermally (ID) in 4 sites (~20x106 cells total); and post-inoculation interferon-α (10,000 units ID into the SV-BR-1-GM inoculation sites) 2±1 and 4±1 days later. Dosing is every 2 weeks for the first month, then monthly for up to one year. This regimen was used in a prior study in 4 evaluable patients with advanced cancer (3 breast and 1 ovarian) and was safe and well tolerated. One patient, who had a partial response of widely metastatic breast cancer, was found to match SV-BR-1-GM at an MHC class II allele (HLA-DRB3*02:02).
This regimen is being used in a clinical trial (NCT03066947 in ClinicalTrials.gov) in patients with advanced breast cancer. To date 7 patients with metastatic breast cancer have been recruited and 6 dosed with evidence of tumor response in 2 patients. Ages ranged from 46-73. Time from initial diagnosis ranged from 2 - 12 years. The number of prior chemotherapy or biological therapy regimens ranged from 3-7. Treatment was generally safe and well tolerated. The majority of adverse events were limited to local irritation at the injection sites. No serious adverse events related to SV-BR-1-GM treatment have been reported and no new or unexpected safety issues related to SV-BR-1-GM have been observed. Two patients dropped out after a single cycle of treatment. One patient with inflammatory breast cancer dropped out after 2 treatments due to worsening breast inflammation. One patient appeared to be responding in the breast after the first treatment, with regression of soft tissue lesions in the breast, but developed a worsening pleural and pericardial effusions shortly after the second treatment with the development of pulseless electrical activity and was unable to be resuscitated. One patient has received 5 cycles of therapy and is ongoing. One patient had a notable response. For this 73-year-old woman with breast cancer diagnosed in 1995 with liver and lung metastases and 7 prior rounds of chemotherapy, after 3 months of treatment her scans noted “a clear response in the multiple bilateral pulmonary nodules” indicating that several lung tumors had disappeared or decreased in size. This response was maintained after 6 months. The liver tumors were stable to slightly increased at 3 months, and then progressed after 6 months. This patient matched with SV-BR-1-GM at 2 HLA loci (HLA-A*24:02 and HLA-DRB3*02:02).
The regimen used in this study has shown early evidence of activity in these patients with late stage, heavily pre-treated metastatic breast cancer. HLA matching may be useful in predicting those patients most likely to respond.
Citation Format: Jarrod P. Holmes, Elizabeth Tan-Chiu, Charles L. Wiseman, Markus D. Lacher, George Peoples, William V. Williams. Safety and efficacy of a whole-cell targeted immunotherapy for breast cancer: Preliminary findings [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT171.