Abstract P2-09-09: Initial safety and efficacy of a phase I/IIa trial of a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer
Authors: Bhattacharya S , Holmes JP , Calfa C , Lukas J , Tan-Chiu E , Clifton GT , Peoples GE , Lacher M , Wiseman CL , Williams WV 
Published: May 2019

Abstract
Background: SV-BR-1-GM is a GM-CSF transfected breast cancer cell line which expresses HLA class I & II antigens. In a previous clinical trial, a partial response of widely metastatic breast cancer was seen in a patient who matched SV-BR-1-GM at HLA-DRB3*02:02. Here we report the safety and efficacy analysis with immunologic correlates of response in the initial patients in a phase I/IIa trial of SV-BR-1-GM in patients with advanced breast cancer
Methods: This phase I/IIa trial enrolled patients with recurrent and/or metastatic breast cancer refractory to standard chemotherapy/targeted-therapy. Patients received low-dose cyclophosphamide 2-3d prior to intradermal injection of SV-BR-1-GM (20x106 cells divided into 4 sites) and interferon-α into the inoculation sites (10,000 IU/site) ˜2 & 4 days subsequently. Cycles were 2 weeks x3 then q mo x 3. Adverse events (AE) were evaluated after each inoculation and graded via CTCAE v4.03. Immunologic response was measured by delayed type hypersensitivity (DTH) after each inoculation. Disease response was evaluated radiographically q3 mo and as clinically indicated (clinical trial NCT03066947).
Results: To date, twenty-two patients have been enrolled and 17 have been inoculated for a total of 39 SV-BR-1-GM inoculations given. Per inoculation, the maximum related AE was grade 1 in 64%, grade 2 in 7.7%, and grade 3 in 7.7%. There were no related grade &gt;3 or unexpected AE. Efficacy data is available on the first six (Table). Tumor regression was seen in 2 patients. 01-002 presented with liver, bone and 20 classic miliary lung metastases (up to 9mm). This subject previously received 7 chemotherapy regimens. She matched SV-BR-1-GM at Class I & II HLA loci. Imaging at 3 mo showed virtually complete regression of all 20 identifiable lesions in the lungs. This response was maintained at 6 mo but the subject was taken off protocol because of disease progression (liver and bone). 01-005, matching HLA-A*24:02, had notable regression of cutaneous lesions, but progressed in pleural and pericardial effusions, had irreversible cardiac arrest (unlikely related). DTH increased in 01-002 from 4mm (first dose) to 47mm (8th dose). Three of 3 patients evaluated developed antibodies responses (as measured by flow cytometry with SV-BR-1) including 01-002. Interleukin 8 also increased in 01-002.
Conclusions: SV-BR-1-GM in this regimen appears to be safe and well-tolerated. In this initial exploratory analysis, SV-BR-1-GM can produce regression of pre-treated metastatic breast cancer correlating with an immunologic response. HLA matching is being evaluated as a predictor of response.
PatientAgeMetastatic Sites# Prior RegimensHLA Matches# of CyclesTumor Regression?01-00146Pleura, Lymph Nodes7 chemo/bio, 5 hormonalDRB3*02:021No01-00273Lung, Liver, Bone6 chemo, 1 hormonalA*24:02, DRB3*02:028Lungs01-00554Lymph nodes, Pleura, Skin3 chemo/bioA*24:022Skin02-00170Lymph nodes1 chemo/bioNone1No02-00361Bone, Brain3 chemoNone6No02-00474Lymph nodes, Cutaneous3 chemo/bio, 1 hormonalDRB3*02:022Lost to Follow-up
Citation Format: Bhattacharya S, Holmes JP, Calfa C, Lukas J, Tan-Chiu E, Clifton GT, Peoples GE, Lacher M, Wiseman CL, Williams WV. Initial safety and efficacy of a phase I/IIa trial of a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P2-09-09.