A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer

Open-label Phase 1/2a study. Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a check point inhibitor (CPI). During the monotherapy phase of Phase 1, one patient will be treated intradermally every 2 weeks for 6 weeks (4 doses) with an initial dose of the BC1 cell line. If this dose is tolerated, the next patient will receive an increased dose of BC1 cells. If once again tolerated, the third patient will receive a further increased dose of BC1. Once at least 3 patients have been safely treated with the BC1 cell line, with no dose-limiting toxicity (DLT), the combinational phase of the study will commence. Following the monotherapy phase, patients will be treated with BC1 and the Bria-OTS regimen (see below) every 3 weeks, plus a CPI at the FDA approved labelled dose and schedule. There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risk(s). During the Phase 1 combination and Phase 2 expansion phases, all patients will be treated with BC1 cells as part of the Bria-OTS regimen, which includes cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell inoculation, and peginterferon alpha-2a administered on the same day, following BC1 cell inoculation. Imaging studies will be performed at screening for baseline prior to first treatment; after the completion of the monotherapy phase just before starting the combination phase, and subsequently every 9 weeks for the first 6 months then q12 weeks thereafter while on treatment. Patients who develop progressive disease on imaging, may remain on treatment as long as the Investigator feels they are deriving clinical benefit and there is no reasonable, meaningful, clinical alternative therapy available. Subjects will continue to be followed for time on subsequent therapy (PFS2) and survival by phone call or medical record review, every 3 months for up to 2 years. Study Drug, Dosage, and Mode of Administration: The Part 1 monotherapy phase of Phase 1 will proceed as follows for each patient: Subject 1, Q2w for 4 doses Subject 2, Q2w for 4 doses Subject 3, Q2w for 4 doses Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment. If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. If none of the patients in the expanded cohort experience a DLT (DLT rate of 1/4), the study will move into Bria-OTS and CPI combination. The dose for the combination will be either the highest dose at which no DLT is observed among the first 3 patients or the 3 patient expanded cohort dose level. In Phase 1, DLTs for determining the combinational BC1 dose will be observed until the first scheduled assessment. If the Phase 1 DLT rate is ≥ 2/4, an additional 3 patients will be dosed using the next lower dose level or 10 million cells (whichever is higher). If none of the 3 subjects experience dose-limiting toxicities (DLTs), that determined BC1 MTD dose will be included in the Part 2 combinational phase of Phase 1 along with a CPI. If a tolerated dose for BC1 cell line cannot be identified, further investigation will be paused, the data reviewed and may resume at a lower dose only with protocol amendment and IRB approval. Following the Phase 1, Part 1 monotherapy phase, 3 patients will be treated every 3 weeks with the Bria-OTS regimen with a CPI in the Part 2 combination phase. The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI on the same day of the cell inoculation according to approved dosing. Once 3 patients have been safely treated with the Bria-OTS regimen and CPI for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI).