Breast cancer grade and clinical benefit in patients with advanced breast cancer treated with an engineered whole tumor cell-targeted immunotherapy alone or in combination with checkpoint inhibition.

3033 Background: SV-BR-1 is a breast cancer cell line derived from a grade II (moderately differentiated) tumor. SV-BR-1 was transfected with the CSF2 gene (encoding GM-CSF) to form SV-BR-1-GM. SV-BR-1-GM expresses HLA class I & II antigens and has functional antigen-presenting cell activity, directly stimulating CD4+ T cells in an HLA-DR restricted fashion. The SV-BR-1-GM regimen consists of low-dose cyclophosphamide (300 mg/m2) to reduce immune suppression, intradermal inoculation with irradiated SV-BR-1-GM (20x106 cells divided into 4 sites) and interferon-α2b (10,000 IU into each inoculation site ~2 & 4 days later) to boost the response. Here, we evaluate the impact of tumor grade on clinical benefit following treatment with the SV-BR-1-GM regimen. Methods: Patients with advanced breast cancer were treated with either the SV-BR-1-GM regimen alone or with the SV-BR-1-GM regimen with pembrolizumab. For the SV-BR-1-GM regimen alone, cycles were administered every 2 weeks x 3 and then monthly, while combination with pembrolizumab (200 mg IV 1-5 days following SV-BR-1-GM inoculation) administered cycles every 3 weeks. Tumor restaging was every 6-12 weeks. Results: 33 patients were enrolled. The treatment was generally safe with inoculation site pruritis, erythema and induration the most common adverse events. 23 patients had grade III (poorly differentiated) tumors, 9 had grade II tumors and one had a grade I (well differentiated) tumor. None of the patients with grade III tumors exhibited clinical benefit. 7 patients with grade I/II tumors received the SV-BR-1-GM regimen alone, 2 received the SV-BR-1-GM regimen with pembrolizumab and 1 received both regimens. As noted in the Table, 7 patients experienced clinical benefit including all 3 patients treated in combination with pembrolizumab. This included 6 patients with stable disease and one with a partial response. Conclusions: The SV-BR-1-GM regimen with or without pembrolizumab appears safe and able to induce clinical benefit even in very heavily pre-treated patients with low or intermediate grade advanced breast cancer. Clinical trial information: NCT03328026 . [Table: see text]