A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
brief summary
This is an 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 clinically available 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. If once again tolerated, the third patient will receive a further dose increase of the 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.
detailed description
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