Abstract P3-09-08: Efficacy and safety of a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer alone and in combination with immune checkpoint inhibitors
Authors: Williams William , Dakhil Shaker R , Holmes Jarrod P , Bhattacharya Saveri , Calfa Carmen , Kundra Ajay , Adams Daniel L , DaSilva Diane , Peoples George E , Sunkari Vivek , Lacher Markus , Wiseman Charles L 
Published: March 2020

Abstract
Background: SV-BR-1-GM is a GM-CSF transfected breast cancer cell line, exceptional for having antigen-presenting capability expressing both HLA I and II. We report clinical efficacy, safety, and immunologic correlates of response from our initial Phase I/II trial and initial data from our trial of SV-BR1-GM in combination with immune checkpoint inhibitors. Methods: We enrolled patients with recurrent and/or metastatic breast cancer refractory to standard therapy. Patients received cyclophosphamide 300 mg/m2 2-3d prior to intradermal injection of SV-BR-1-GM (20-40 × 106 cells divided into 4 sites) and IFNα into the inoculation sites (10,000 IU/site) ~2 & 4 days subsequently. Cycles were q2 weeks x3 then qmo x 3. Adverse events (AE) were evaluated after each inoculation. Immunologic responses were measured by delayed type hypersensitivity (DTH) after each inoculation with humoral and cellular responses evaluated ~q3 mo. Disease response was evaluated radiographically q3 mo and as clinically indicated (clinical trial NCT03066947). A similar regimen was used with SV-BR-1-GM in combination with pembrolizumab (200 mg IV) with cycles every 3 weeks (Phase I/II study NCT03328026). Results: In Phase I/IIa (NCT03066947), 23 patients underwent 1 - 8 cycles of treatment. Tumor regression was seen in 3 patients, all of whom matched SV-BR-1-GM at least at one HLA allele. There were no related serious adverse events. The most common adverse event was minor local irritation at the inoculation site. Clinical data are shown in the table. A measurable DTH response was present in 21 patients. Of patients who developed a DTH response and had at least one HLA match, the tumor regression rate was 33% and for those with 2 HLA matches 67%. We saw evidence of antibody responses in 3 of 5 patients evaluated to date. Especially in responders after treatment, blood lymphocytes showed increased cytokine secretion (including ITAC, IFNγ, IL-6 & IL-8) following stimulation with antigens expressed in SV-BR-1-GM. 21/23 patients had expression of PD-L1 in identified circulating cancer-associated cells, and expression levels increased with treatment. Therefore, a combination study with pembrolizumab was initiated. Data on the first 6 patients shows that the regimen is clinically active and safe. One patient with a robust DTH response had evidence of tumor regression in liver metastases. This study is ongoing and is being modified to evaluate combination therapy with the PD-1 inhibitor INCMGA00012 and the IDO inhibitor epacadostat. Conclusions: SV-BR-1-GM appears to be safe and well-tolerated. Contrary to conventional wisdom, SV-BR-1-GM can produce regression of metastatic breast cancer correlating with an immunologic response and HLA matching. Combination therapy with checkpoint inhibitors is ongoing.
Citation Format: William Williams, Shaker R Dakhil, Jarrod P Holmes, Saveri Bhattacharya, Carmen Calfa, Ajay Kundra, Daniel L Adams, Diane DaSilva, George E Peoples, Vivek Sunkari, Markus Lacher, Charles L Wiseman. Efficacy and safety of a modified whole tumor cell targeted immunotherapy in patients with advanced breast cancer alone and in combination with immune checkpoint inhibitors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P3-09-08.