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.
Histological confirmed recurrent metastatic breast cancer which has failed prior
Human epidermal growth factor 2 (EGFR2, HER2) positive tumors must have failed therapy with at least 2 anti-HER2 agents
HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy and previously treated with at least 2 hormone based targeted therapy containing regimens.
Triple-negative and inflammatory tumors must have exhausted other curative intent therapies including prior treatment with a taxane and platinum-based agent
Concurrent anti-cancer treatment.
Recent chemotherapy, radiotherapy, or other anti-cancer treatment within 3 weeks of first protocol treatment.
Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
History of clinical hypersensitivity to the designated therapy, as specified in the protocol or to any components used in the preparation of any cell line in this study.
Sequential
BC1 cell line
Biological/VaccineBC1 cell line is a different experimental, HER-2 positive, allogeneic, whole cell BC cell lines designed to secrete GM-CSF in situ and augment dendritic cell activity. Similar to the SV-BR-1-GM cell line (NCT03328026, IND 10312), the BC cell line is derived from the BC parent cell line, SV-BR-1, which expresses multiple tumor associated antigens (TAAs)
Bria-OTS regimen and CPI (tislelizumab)
Biological/VaccineBiological: BC1 * BC1 inoculation intradermally at 4 sites Drug: Low dose cyclophosphamide * Pretreatment with low dose cyclophosphamide 2-3 days prior to BC1 inoculation Drug: Interferon * Subjects will receive low dose peginterferon alpha-2a on the same day as cell inoculation. Drug: Tislelizumab * CPI treatment will also be given on the same day as cell inoculation.
Bria-OTS regimen and CPI (tislelizumab) expansion cohort
Biological/VaccineBiological: BC1 * BC1 inoculation intradermally at 4 sites Drug: Low dose cyclophosphamide * Pretreatment with low dose cyclophosphamide 2-3 days prior to BC1 inoculation Drug: Interferon * Subjects will receive low dose peginterferon alpha-2a on the same day as cell inoculation. Drug: Tislelizumab * CPI treatment will also be given on the same day as cell inoculation.
Safety as assessed by adverse events (AEs), including serious adverse events (SAEs)
Total number of AEs
Evaluate the Proportion of Patients with Abnormalities in Safety Laboratory Parameters that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab)
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters
Evaluate changes in the electrocardiogram QT interval that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab). [Safety]
To evaluate the safety of BC1 as assessed by: o Electrocardiograms (ECG) with measurement of the QT interval
Evaluate the proportion of patients with abnormal physical examination findings including vital signs
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Physical Examination Findings and Abnormal Vital Signs
Tumor response as assessed by Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Quantify tumor ORR
Tumor response as assessed by Clinical response rate as determined by local standard of care imaging and investigators
Determine clinical relevance of tumor response
Tumor response as assessed by Non-progressive rate (aka: clinical benefit rate), defined as CR, PR, or stable disease (SD) per RECIST 1.1 and as determined by local standard of care imaging and investigators
Quantify change in tumor rate of progression
Tumor response as assessed by Duration of response (DoR)
Quantify tumor duration of response to therapy
PFS and OS treated with HLA-characterized cellular immunotherapy
To evaluate the effect of the BC1 on progression-free survival (PFS) • To assess the single agent activity of the BC1 regimen in the sample cohort using PFS, ORR, and CBR, and changes in circulating tumor cells before and after therapy.
Evaluate Immune Responses
Immune responses will be evaluated by known and hypothesized covariates including DTH
Stratified Analysis of Outcomes by HLA type
Determine specific HLA type for analysis
Stratified Analysis of Outcomes by Tumor Grade
Classify the tumor based on its differentiation: * well-differentiated or Grade 1 * moderately differentiated or Grade 2 * poorly differentiated or Grade 3
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