Predictors Of Response To A Modified Whole Tumor Cell Immunotherapy In Patients With Advanced Breast Cancer From Two Phase I/Iia Trials.

Abstract Objectives: SV-BR-1-GM is a GM-CSF secreting breast cancer cell line derived from a Grade II (moderately differentiated) breast tumor that also expresses HLA class I & II antigens and is able to function as an antigen-presenting cell. Irradiated SV-BR-1-GM is used in a regimen including pre-dose low-dose cyclophosphamide and post-dose local IFN-α2b. The SV-BR-1-GM regimen has been used alone (“monotherapy”, ClinicalTrials.gov NCT03066947 - study completed) and in combination with checkpoint inhibitors (“combination”, ClinicalTrials.gov NCT03328026 - study ongoing). The objective is to evaluate potential predictors of response in advanced metastatic breast cancer (aMBC). Methodology: 23 patients with refractory aMBC were treated with the SV-BR-1-GM regimen as monotherapy (cycles every 2 weeks x3 and then monthly). The combination study uses the SV-BR-1-GM regimen with PD-1 inhibitors pembrolizumab or INCMGA00012 with cycles every 3 weeks (12 patients dosed to date). Analyses include circulating tumor cells (CTCs), cancer-associated macrophage-like cells (CAMLs), tumor Grade (well- (Grade I), moderately- (Grade II) or poorly differentiated (Grade III)), HLA-type, and the ability to develop delayed-type hypersensitivity (DTH).Preliminary Data: The patients were heavily pre-treated (median of 4 prior systemic therapies not including hormonal therapy). In the monotherapy study, disease control (including SD, PR or CR) was seen in 6 patients (26%, all with SD). 16 patients (76%) developed measurable DTH (2 patients with no data). In the combination therapy study, disease control was seen in 3 patients (25%, 1 PR and 2 SD) and 10 (91%) developed DTH. In the combined studies, patients with Grade I or Grade II tumors were more likely to achieve disease control (6/9, 67%) compared with those with Grade III tumors (2/20, 10%). Median progression free survival (PFS) on monotherapy was 2.6 months and 4.5 months for patients with Grade I/II disease. Median PFS on the combination study was 4.2 months and 6.9 months for patients with Grade I/II tumors. Patients with 1 or 2 HLA matches with SV-BR-1-GM achieved disease control in 29% (6/21) and 38% (5/13), respectively. In patients with Grade I or II tumors, for those with 1+ or 2+ HLA matches, disease control was seen in 57% (4/7) and 75% (3/4), respectively. None of the 3 patients with high levels of CTCs at baseline had disease control. Mean and median PD-L1 expression levels on CTCs and CAMLS were higher for patients with Grade III tumors compared with Grade I/II tumors, but this was not clearly correlated with clinical response.The SV-BR-1-GM regimen can produce disease control and clinical benefit in very heavily pretreated patients with aMBC refractory to conventional therapies especially if the patients have an intact immune system (DTH), do not have high levels of CTCs, have Grade I or II disease, and have HLA matching with the SV-BR-1-GM cell line. Citation Format: William V. Williams, Markus D. Lacher, Daniel L. Adams, Shaker R. Dakhil, Jarrod P. Holmes, Saveri Bhattacharya, Carmen Calfa, George E. Peoples, Charles L. Wiseman. Predictors of response to a modified whole tumor cell immunotherapy in patients with advanced breast cancer from two phase I/IIa trials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr CT102.