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.
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. A secondary objective will be to evaluate the activity of the Bria-IMT regimen alone in comparison with the Bria-IMT regimen in combination with CPI. Initial randomization will be 1:1:1 to the Bria-IMT regimen + CPI (combination therapy), TPC, and the Bria-IMT regimen alone (monotherapy). After the first 150 patients have enrolled in the study, the monotherapy arm will be discontinued and patients allowed to cross over to the combination therapy if needed. Randomization will continue 1:1 between the combination therapy vs TPC. For the Bria regimen +/- CPI arms, treatment cycles occur every 3 weeks. TPC cycle details will be according to the site's SOC. In the absence of progressive disease or major safety issues, the patient will continue with therapy cycles, with imaging assessment every 6 weeks x2 then every 8 weeks thereafter. The Bria-IMT regimen includes: Day -2 or -3 Cyclophosphamide 300mg/m2 Day 0 SV-BR-1-GM given intradermally divided into 4 inoculations Day 1-3 CPI infusion plus interferon intra-dermally within each Bria-IMT inoculation site
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
404
SV-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 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 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 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.
Patients 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.
Mayo Clinic-Comprehensive Cancer Center-Breast Clinic
Phoenix, Arizona, United States
RECRUITINGUniversity of Arizona-Cancer Center
Tucson, Arizona, United States
RECRUITINGLos Angeles cancer Network_Anaheim
Anaheim, California, United States
RECRUITINGComprehensive Blood and Cancer Center
Bakersfield, California, United States
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.
Time frame: Up to 60 months
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
Time frame: Up to 60 months
Clinical Benefit Rate (CBR)
To evaluate the efficacy of the Bria-IMT regimen with CPI using Clinical Benefit Rate (CBR)
Time frame: Up to 60 months
Overall response rate (ORR)
To evaluate the efficacy of the Bria-IMT regimen with CPI using best overall response rate (ORR)
Time frame: Up to 60 months
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.
Time frame: Up to 60 months
CNS Event free survival (EFS)
CNS event free survival for subjects with and without known CNS metastases at baseline
Time frame: Up to 60 months
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Cedars-Sinai Cancer Beverly Hills
Beverly Hills, California, United States
RECRUITINGLos Angeles Cancer Network_Corona
Corona, California, United States
RECRUITINGLos Angeles cancer Network_Fountain Vallley
Fountain Valley, California, United States
RECRUITINGLos Angeles Cancer Network_Glendale
Glendale, California, United States
RECRUITINGHoag Hospital Center
Irvine, California, United States
RECRUITINGHoag Hospital Irvine
Irvine, California, United States
RECRUITING...and 67 more locations