Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer.
Purpose
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.
Conditions
- Breast Cancer
- Metastatic Breast Cancer
- Breast Neoplasm
- Breast Cancer Metastatic
- End Stage Cancer
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Be ≥ 18 years of age. 2. Have signed informed consent. 3. Have histological confirmation of breast cancer with either locally recurrent unresectable and/or metastatic lesions, and have failed prior therapy: - Patients with persistent disease and local recurrence must not be amenable to local treatment. - For patients with metastatic disease, late-stage MBC with no meaningful alternative therapies available and the following class specific treatment histories: 1. 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. 2. Estrogen receptor (ER), progesterone receptor (PR) positive tumors: must be refractory to hormonal therapy demonstrated by progression on at least 2 hormonal agents in 2 separate lines of hormone directed therapy. 3. Triple Negative tumors: Must have exhausted all curative intent therapies including at least 2 prior chemotherapy regimens, which can include regimens in neoadjuvant and adjuvant settings. 4. Cancers with known germline or genomic actionable targets, e.g. g/mBRCA, must have been treated with all tumor directed indicated treatment e.g. PARPi, if tolerated. 5. HER2 low patients, in addition to the appropriate therapies based on ER/PR status and germline or genomic actionable targets, must also have received at least one HER2-targeted agent approved for treatment of HER2 low patients. 6. HER2 negative tumors must be refractory to hormonal therapy (if indicated) and previously treated with at least 2 chemotherapy regimens. 7. Patients with new or progressive breast cancer metastatic to the brain will be eligible provided: - The brain metastases must be clinically stable (without evidence of progressive disease by imaging for at least 4 weeks prior to first dose) - There is no need for steroids and patients have not had steroids for at least 2 weeks prior to the first dose - Tumor is not impinging on Middle Cerebral Artery/speech-motor strip - If surgically debulked, must be healed with at least 3 weeks since surgery prior to the first dose 4. Has expected survival of at least 4 months. 5. ECOG performance status of 0, 1 or 2
Exclusion Criteria
- Concurrent or recent chemotherapy, immunotherapy or major surgery within 21 days prior to the first dose. 2. Radiotherapy within 14 days of the first dose of study treatment. 3. 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). 4. 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), . 5. Toxicity to prior CPI that has not resolved to grade 1 or less except for stable asymptomatic endocrinopathies. 6. History of clinical hypersensitivity to the designated therapy as specified in the protocol, including the proposed TPC, beef, or to any components used in the preparation of SV- BR-1-GM. 7. History of hypersensitivity to any of the therapies proposed for treatment in this study. 8. Serum creatinine OR Measured OR calculated Creatinine Clearance (CrCl) (GFR can also be used in place of creatinine or CrCl) >2.0 × ULN or <30 mL/min for participants with creatinine levels >2.0 × institutional ULN. 9. Absolute granulocyte count <1000; platelets <80,000; hemoglobin ≤ 7 g/L. 10. Bilirubin ≥ 2 × ULN unless conjugated bilirubin ≤ ULN; alkaline phosphatase >5x upper limit of normal (ULN); ALT/AST >3x ULN. For patients with hepatic metastases, ALT/AST >5x ULN is exclusionary. 11. INR or PT or aPTT > 1.8 × ULN, unless the participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulants. 12. Receiving any medication listed in the prohibited medication section of the protocol. 13. Proteinuria >2+ on urinalysis 14. A history or presence of an abnormal electrocardiogram (ECG) that, in the Investigator's opinion, is clinically meaningful. Screening corrected QT interval (QTc) interval >480 milliseconds is excluded (corrected by Fridericia or Bazett formula). In the event that a single QTc is >480 milliseconds, the participant may enroll if the average QTc for the 3 ECGs is <480 milliseconds. 15. New York Heart Association stage 3 or 4 cardiac disease. 16. A pericardial effusion of moderate severity or worse. 17. Symptomatic pleural effusion or ascites. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible. 18. Any woman of childbearing potential (i.e., has had a menstrual cycle within the past year and has not been surgically sterilized), unless she agrees to take appropriate precautions to avoid becoming pregnant during the study and has a negative serum pregnancy test within 7 days prior to starting treatment. 19. Men must have been sterile or, if they were potentially fertile/reproductively competent, should take appropriate precautions to avoid fathering a child for the duration of the study. 20. Women who are pregnant or nursing. 21. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 2 years of study entry with the exception of cured basal cell or squamous cell carcinoma of the skin, superficial bladder cancer, prostate intraepithelial neoplasm, carcinoma in situ of the cervix, or other noninvasive or indolent malignancy, or cancers from which the participant has been disease-free for > 1 year, after treatment with curative intent. 22. Patients who have uncontrolled HIV or have clinical or laboratory features indicative of AIDS. 23. Have a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (doses exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study treatment. 24. Have an active autoimmune disease that has required systemic treatment in past year (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is allowed. 25. Known active HAV, HBV, or HCV infection, as defined by elevated transaminases with the following serology: positivity for HAV IgM antibody, anti-HCV, anti-HBc IgG or IgM, or HBsAg (in the absence of prior immunization). 26. Active infections requiring systemic therapy within the past 14 days. 27. Patients with severe psychiatric disease (e.g., schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator in consultation with the Medical Monitor. 28. Has received a live vaccine within 28 days of the first dose of study drug. 29. Patients may not be on a concurrent clinical trial, unless approved by the Investigator.
Study Design
- Phase
- Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Bria-IMT Regimen + CPI |
The Bria-IMT regimen: 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 administered intra-dermally within each SV-BR-1-GM inoculation site |
|
|
Active Comparator Treatment of Physician's Choice |
TPC consists of eribulin, carboplatin, capecitabine, gemcitabine, vinorelbine or taxanes in accordance with the investigators' and institutional standard of care. The specific details of the selected regimen must include every detail of administration including frequency, sequencing (for multi-agent regimens), duration of infusion or oral administration, planned dose, dose prescribed, dose administered, dose adjustments after initial prescription or start of TPC treatment, and any other change in TPC from its initial election prior to randomization. |
|
|
Experimental Bria-IMT Regimen Alone |
The Bria-IMT regimen: 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 administered intra-dermally within each SV-BR-1-GM inoculation site |
|
Recruiting Locations
Mayo Clinic-Comprehensive Cancer Center-Breast Clinic
Phoenix 5308655, Arizona 5551752 85054
Phoenix 5308655, Arizona 5551752 85054
University of Arizona-Cancer Center
Tucson 5318313, Arizona 5551752 85719
Tucson 5318313, Arizona 5551752 85719
Los Angeles cancer Network_Anaheim
Anaheim 5323810, California 5332921 92801
Anaheim 5323810, California 5332921 92801
Comprehensive Blood and Cancer Center
Bakersfield 5325738, California 5332921 93309
Bakersfield 5325738, California 5332921 93309
Cedars-Sinai Cancer Beverly Hills
Beverly Hills 5328041, California 5332921 90211
Beverly Hills 5328041, California 5332921 90211
Los Angeles Cancer Network_Corona
Corona 5339631, California 5332921 92879
Corona 5339631, California 5332921 92879
Los Angeles cancer Network_Fountain Vallley
Fountain Valley 5350207, California 5332921 92708
Fountain Valley 5350207, California 5332921 92708
Los Angeles Cancer Network_Glendale
Glendale 5352423, California 5332921 91206
Glendale 5352423, California 5332921 91206
Hoag Hospital Center
Irvine 5359777, California 5332921 92618
Irvine 5359777, California 5332921 92618
Hoag Hospital Irvine
Irvine 5359777, California 5332921 92618
Irvine 5359777, California 5332921 92618
Los Angeles Cancer Network
Los Angeles 5368361, California 5332921 90017
Los Angeles 5368361, California 5332921 90017
Cedars-Sinai Cancer at Cedars-Sinai Medical Facility
Los Angeles 5368361, California 5332921 90048
Los Angeles 5368361, California 5332921 90048
Los Angeles Cancer Network_Century City
Los Angeles 5368361, California 5332921 90067
Los Angeles 5368361, California 5332921 90067
UCLA-Hematology/Oncology Medical Plaza
Los Angeles 5368361, California 5332921 90095
Los Angeles 5368361, California 5332921 90095
UCLA-Hematology/Oncology_LA 2
Los Angeles 5368361, California 5332921 90095
Los Angeles 5368361, California 5332921 90095
UCLA-Hematology/Oncology_LA
Los Angeles 5368361, California 5332921 90095
Los Angeles 5368361, California 5332921 90095
Los Angeles Cancer Network_Pasadena
Pasadena 5381396, California 5332921 91105
Pasadena 5381396, California 5332921 91105
Los Angeles cancer Network_Riverside
Riverside 5387877, California 5332921 92501
Riverside 5387877, California 5332921 92501
UC San Diego
San Diego 5391811, California 5332921 92037
San Diego 5391811, California 5332921 92037
St. John's Cancer Center
Santa Monica 5393212, California 5332921 90404
Santa Monica 5393212, California 5332921 90404
UCLA-Department of Medicine Hematology/Oncology-Parkside
Santa Monica 5393212, California 5332921 90404
Santa Monica 5393212, California 5332921 90404
UCLA-Hetamtology/Oncology_S Monica
Santa Monica 5393212, California 5332921 90404
Santa Monica 5393212, California 5332921 90404
Torrance Memorial Cancer Center
Torrance 5403022, California 5332921 90505
Torrance 5403022, California 5332921 90505
Los Angeles Cancer Network_Valley Pres
Van Nuys 5405693, California 5332921 91405
Van Nuys 5405693, California 5332921 91405
Cedars-Sinai Breast Health Services Building
West Hollywood 5408076, California 5332921 90048
West Hollywood 5408076, California 5332921 90048
Smilow Cancer Hospital at Yale New Haven
New Haven 4839366, Connecticut 4831725 06511
New Haven 4839366, Connecticut 4831725 06511
University of Miami _SCCC - Aventura
Aventura 4146429, Florida 4155751 33180
Aventura 4146429, Florida 4155751 33180
University of Miami-SCCC-Lennar
Coral Gables 4151871, Florida 4155751 33146
Coral Gables 4151871, Florida 4155751 33146
University of Miami_SCCC-Coral Springs
Coral Springs 4151909, Florida 4155751 33065
Coral Springs 4151909, Florida 4155751 33065
University of Miami Hospital and Clinics - Deerfield Beach
Deerfield Beach 4153071, Florida 4155751 33442
Deerfield Beach 4153071, Florida 4155751 33442
University of Miami_SCCC-Hollywood
Hollywood 4158928, Florida 4155751 33021
Hollywood 4158928, Florida 4155751 33021
Mayo Clinic Florida-Comprehensive Cancer Center
Jacksonville 4160021, Florida 4155751 32224
Jacksonville 4160021, Florida 4155751 32224
University Of Miami-SCCC-Miami
Miami 4164138, Florida 4155751 33136
Miami 4164138, Florida 4155751 33136
University of Miami_SCCC - Kendall
Miami 4164138, Florida 4155751 33176
Miami 4164138, Florida 4155751 33176
Advent Health - Orlando
Orlando 4167147, Florida 4155751 32804
Orlando 4167147, Florida 4155751 32804
University of Miami-SCCC-Plantation
Plantation 4168782, Florida 4155751 33324
Plantation 4168782, Florida 4155751 33324
Winship Cancer Institute of Emory University
Atlanta 4180439, Georgia 4197000 30322
Atlanta 4180439, Georgia 4197000 30322
Northwestern University
Chicago 4887398, Illinois 4896861 60611
Chicago 4887398, Illinois 4896861 60611
Southern Illinois University-Simmons
Springfield 4250542, Illinois 4896861 62702
Springfield 4250542, Illinois 4896861 62702
Carle Foundation Cancer Institute-Urbana
Urbana 4914570, Illinois 4896861 61801
Urbana 4914570, Illinois 4896861 61801
Northwest Cancer Center
Dyer 4919820, Indiana 4921868 46311
Dyer 4919820, Indiana 4921868 46311
AMR Kansas City Oncology
Kansas City 4273837, Kansas 4273857 66204
Kansas City 4273837, Kansas 4273857 66204
Care Access-Marrero
Marrero 4332628, Louisiana 4331987 70072
Marrero 4332628, Louisiana 4331987 70072
The Center for Cancer and Blood Disorders a division of American Oncology Partners, P.A.
Bethesda 4348599, Maryland 4361885 20817
Bethesda 4348599, Maryland 4361885 20817
Mayo Clinic-Comprehensive Cancer Center-Breast Clinic
Rochester 5043473, Minnesota 5037779 55905
Rochester 5043473, Minnesota 5037779 55905
Nebraska Cancer Specialists
Omaha 5074472, Nebraska 5073708 68130
Omaha 5074472, Nebraska 5073708 68130
Dartmouth Hitchcock Medical Center
Lebanon 5088597, New Hampshire 5090174 03756
Lebanon 5088597, New Hampshire 5090174 03756
Hunterdon Medical Center
Flemington 5098124, New Jersey 5101760 08822
Flemington 5098124, New Jersey 5101760 08822
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Babylon)
Babylon 5107612, New York 5128638 11702
Babylon 5107612, New York 5128638 11702
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(New Hyde Park)
New Hyde Park 5128514, New York 5128638 11042
New Hyde Park 5128514, New York 5128638 11042
Manhattan Hematology /Oncology Associates
New York 5128581, New York 5128638 10016
New York 5128581, New York 5128638 10016
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (NY)
New York 5128581, New York 5128638 10028
New York 5128581, New York 5128638 10028
New York Cancers & Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Patchogue)
Patchogue 5130672, New York 5128638 11772
Patchogue 5130672, New York 5128638 11772
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Port Jefferson Station2)
Port Jefferson Station 5132015, New York 5128638 11776
Port Jefferson Station 5132015, New York 5128638 11776
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(Port Jefferson Station1)
Port Jefferson Station 5132015, New York 5128638 11776
Port Jefferson Station 5132015, New York 5128638 11776
New York Cancers & Blood Specialists
Port Jefferson Station 5132015, New York 5128638 11776
Port Jefferson Station 5132015, New York 5128638 11776
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Riverhead)
Riverhead 5133926, New York 5128638 11901
Riverhead 5133926, New York 5128638 11901
New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Brox)
The Bronx 5110266, New York 5128638 10469
The Bronx 5110266, New York 5128638 10469
Gabrail Cancer & Research Center
Canton 5149222, Ohio 5165418 44718
Canton 5149222, Ohio 5165418 44718
Cleveland Clinic
Cleveland 5150529, Ohio 5165418 44195
Cleveland 5150529, Ohio 5165418 44195
Texas Oncology-Baylor Charles A. Sammons Cancer Center
Dallas 4684888, Texas 4736286 75246
Dallas 4684888, Texas 4736286 75246
Mary Crowley Cancer Research
Dallas 4684888, Texas 4736286 75251
Dallas 4684888, Texas 4736286 75251
DHR Health Oncology Institute
Edinburg 4688275, Texas 4736286 78539
Edinburg 4688275, Texas 4736286 78539
Texas Oncology - Fredericksburg
Fredericksburg 4692279, Texas 4736286 78624
Fredericksburg 4692279, Texas 4736286 78624
Texas Oncology - Harlingen
Harlingen 4696233, Texas 4736286 78550
Harlingen 4696233, Texas 4736286 78550
Texas Oncology McAllen
McAllen 4709796, Texas 4736286 78503
McAllen 4709796, Texas 4736286 78503
Texas Oncology, New Braunfels
New Braunfels 4714131, Texas 4736286 78130
New Braunfels 4714131, Texas 4736286 78130
Texas Oncology-San Antonio Cancer Care
San Antonio 4726206, Texas 4736286 78216
San Antonio 4726206, Texas 4736286 78216
Texas Oncology - San Antonio Northeast
San Antonio 4726206, Texas 4736286 78217
San Antonio 4726206, Texas 4736286 78217
Texas Oncology - San Antonio Stone Oak
San Antonio 4726206, Texas 4736286 78258
San Antonio 4726206, Texas 4736286 78258
Tranquil Clinical Research
Webster 4740423, Texas 4736286 77598
Webster 4740423, Texas 4736286 77598
Texas Oncology - Weslaco
Weslaco 4740629, Texas 4736286 78596
Weslaco 4740629, Texas 4736286 78596
Hematology-Oncology Associates of Fredericksburg, Inc
Fredericksburg 4760059, Virginia 6254928 22408
Fredericksburg 4760059, Virginia 6254928 22408
Cancer Care Northwest-1 (601 S. Sherman)
Spokane 5811696, Washington 5815135 99202
Spokane 5811696, Washington 5815135 99202
Cancer Care Northwest_2 (605 E. Holland)
Spokane 5811696, Washington 5815135 99218
Spokane 5811696, Washington 5815135 99218
Cancer Care Northwest
Spokane Valley 5811729, Washington 5815135 99218
Spokane Valley 5811729, Washington 5815135 99218
Sheboygan Cancer & Blood Specialists
Sheboygan 5272893, Wisconsin 5279468 53081
Sheboygan 5272893, Wisconsin 5279468 53081
More Details
- NCT ID
- NCT06072612
- Status
- Recruiting
- Sponsor
- BriaCell Therapeutics Corporation
Detailed Description
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