Abstract 5588: Clinical and pharmacodynamic responses to a modified whole tumor cell immunotherapy in patients with advanced breast cancer from two phase I-IIa trials
Authors: Sunkari Vivekananda G. , Galeas Jacqueline , Dakhil Shaker R. , Holmes Jarrod , Bhattacharya Saveri , Calfa Carmen J. , Kundra Ajay , Adams Daniel L. , DaSilva Diane , Peoples George E. , Wiseman Charles L. , Williams William V. , Lacher Markus D. 
Published: September 2020

Abstract
SV-BR-1-GM is a GM-CSF secreting breast cancer cell line that also expresses HLA class I & II antigens. Irradiated SV-BR-1-GM is used in a regimen including pre-dose low-dose cyclophosphamide and post-dose local interferon-α2b. The SV-BR-1-GM regimen has been used alone (“Monotherapy” study ClinicalTrials.gov NCT03066947) and in combination with immune checkpoint inhibitors (ongoing combination study ClinicalTrials.gov identifier NCT03328026). Here we report regression of metastatic breast cancer and pharmacodynamic analysis with immunologic correlates.
23 patients with advanced breast cancer refractory to standard therapies were treated with the SV-BR-1-GM regimen in the monotherapy trial with cycles every 2 weeks for the first month and then monthly. The combination study is evaluating the SV-BR-1-GM regimen with checkpoint inhibitors (PD-1 inhibitors pembrolizumab or INCMGA00012) with cycles every 3 weeks (11 patients have been dosed to date). Pharmacodynamic analyses include delayed-type hypersensitivity (DTH), antibodies against SV-BR-1 (precursor of SV-BR-1-GM), blood lymphocyte proliferation (determined using flow cytometry), circulating cytokines in sera and cytokine secretion (Luminex based assays) following stimulation with peptides of antigens expressed in SV-BR-1-GM cells (HER2 and PRAME).
In the monotherapy study, tumor regression was seen in 3 patients. 21 patients developed measurable DTH signifying cellular immunity. Blood lymphocytes from responders after treatment showed increased proliferation and cytokine secretion (GM-CSF, IL-2, IL-21) - following stimulation with HER2 and PRAME peptides. Differential serum cytokine levels were observed (CD40L, MCP-1, IL-1RA) in 5 patients. Increased antibody levels compared to baseline were observed in 6 of the 12 patients assessed. Patients with objective tumor regression had the most pronounced responses. In the combination therapy study, 2 patients have shown objective evidence of tumor regression, including one patient with liver metastases, which decreased by 25%, and one patient with adrenal and dural metastases (29% reduction in target lesion). Both patients had Grade II tumors, similar to the tumor from which SV-BR-1-GM was derived.
These observations confirm the ability of the SV-BR-1-GM regimen to elicit regression of far advanced refractory metastatic breast cancer. No serious toxicities clearly attributed to the SV-BR-1-GM regimen were observed. Pharmacodynamic analysis of humoral and cell-mediated immune responses showed notable upregulation, the strongest responses being seen in those with measurable clinical regression. Patients with Grade I or II tumors appeared more likely to respond.
Citation Format: Vivekananda G. Sunkari, Jacqueline Galeas, Shaker R. Dakhil, Jarrod Holmes, Saveri Bhattacharya, Carmen J. Calfa, Ajay Kundra, Daniel L. Adams, Diane DaSilva, George E. Peoples, Charles L. Wiseman, William V. Williams, Markus D. Lacher. Clinical and pharmacodynamic responses to a modified whole tumor cell immunotherapy in patients with advanced breast cancer from two phase I-IIa trials [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5588.