This is a multicenter randomized, open label study to evaluate overall survival with the Bria-IMT regimen in combination with Checkpoint Inhibitor \[Retifanlimab\], versus Treatment of Patients'/Physicians' Choice (TPC) in advanced metastatic or locally recurrent breast cancer (aMBC) patients with no approved alternative therapies available.
Be ≥ 18 years of age.
Have signed informed consent.
Patients with persistent disease and local recurrence must not be amenable to local treatment.
Human epidermal growth factor 2 (HER2) positive must be previously treated with at least 3 regimens containing at least two anti-HER2 and at least one chemotherapy containing regimen.
Concurrent or recent chemotherapy, immunotherapy or major surgery within 21 days prior to the first dose.
Radiotherapy within 14 days of the first dose of study treatment.
Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of any grade of alopecia and anemia not requiring transfusion support).
Any toxicity to prior CPI that was grade 3 or higher unless it has been successfully treated (e.g. hypothyroidism or hypopituitarism treated with replacement therapy), .
Parallel
SV-BR-1-GM
Biological/VaccineSV-BR-1-GM is an experimental, allogeneic, whole cell breast tumor cell line stably transfected with the CSF2 gene (encoding GM-CSF) to secrete GM-CSF in vivo to consequently augment dendritic cell activity
Cyclophosphamide
DrugCyclophosphamide is an alkylating agent with indications for treatment of malignant diseases including breast cancer. Cyclophosphamide (Cytoxan) 300 mg/m2 I.V., single dose, will be given to patients assigned to the SV-BR-1-GM. Cyclophosphamide will be administered 2-3 days prior to SV-BR-1-GM inoculations.
Interferon infiltration of the inoculation site
DrugInterferon is a cytokine released by cells to regulate immune responses to viral infections. For this study, 0.1 mcg Pegasys per injection site (x 4 injection sites) will be administered.
Retifanlimab
DrugRetifanlimab is a checkpoint inhibitor. A total dose of 375mg will be administered at first cycle on or about day +2 (+/-1d). In all other cycles, Retifanlimab is permitted to be administered between Day -2/-3 to Day 2±1 of the cycle based on the convenience of the patients and the clinical sites. However once the timing of the CPI is chosen for C1, it must be given on the same day thereafter throughout the trial.
Treatment of Physician's Choice
DrugPatients in the TPC arm of the study will be treated with one or a combination of the following: carboplatin, taxanes, capecitabine, gemcitabine, vinorelbine or eribulin in accordance with the investigators and institutional standard of care. For HER2+ patients, a HER2-targeted agent of the physician's choice can be part of TPC.
Overall Survival
To evaluate the effect of the Bria-IMT regimen in combination with Check Point Inhibitor (CPI) on overall survival (OS) compared to treatment of physician's choice (TPC) chemotherapy in patients with metastatic breast cancer with no approved alternative therapies available as per the Inclusion criteria.
Progression-free survival (PFS)
To evaluate the effect of the Bria-IMT regimen with CPI on progression-free survival (PFS) • To assess the single agent activity of the Bria-IMT regimen in the sample cohort using PFS, ORR, and CBR
Clinical Benefit Rate (CBR)
To evaluate the efficacy of the Bria-IMT regimen with CPI using Clinical Benefit Rate (CBR)
Overall response rate (ORR)
To evaluate the efficacy of the Bria-IMT regimen with CPI using best overall response rate (ORR)
Quality of life (QoL)
To compare the effect of the Bria-IMT regimen with CPI on quality of life (QoL) including time without symptoms and time without toxicities (TWiST) adjusted for time on study.
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