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NCT06072612PHASE3Recruiting

Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer.

BriaCell Therapeutics Corporation

Start Date

12/5/2023

Completion Date

6/1/2028

Summary

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.

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

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: 1. 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: 1. 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.

Interventions

BIOLOGICAL

SV-BR-1-GM

DRUG

Cyclophosphamide

DRUG

Interferon infiltration of the inoculation site

DRUG

Retifanlimab

DRUG

Treatment of Physician's Choice

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Conditions

Breast CancerMetastatic Breast CancerBreast NeoplasmBreast Cancer MetastaticEnd Stage Cancer

Locations

Mayo Clinic-Comprehensive Cancer Center-Breast Clinic

Phoenix, Arizona 85054

United States

University of Arizona-Cancer Center

Tucson, Arizona 85719

United States

Los Angeles cancer Network_Anaheim

Anaheim, California 92801

United States

Comprehensive Blood and Cancer Center

Bakersfield, California 93309

United States

Cedars-Sinai Cancer Beverly Hills

Beverly Hills, California 90211

United States

Los Angeles Cancer Network_Corona

Corona, California 92879

United States

Los Angeles cancer Network_Fountain Vallley

Fountain Valley, California 92708

United States

Los Angeles Cancer Network_Glendale

Glendale, California 91206

United States

Hoag Hospital Center

Irvine, California 92618

United States

Hoag Hospital Irvine

Irvine, California 92618

United States

Los Angeles Cancer Network

Los Angeles, California 90017

United States

Cedars-Sinai Cancer at Cedars-Sinai Medical Facility

Los Angeles, California 90048

United States

Los Angeles Cancer Network_Century City

Los Angeles, California 90067

United States

UCLA-Hematology/Oncology Medical Plaza

Los Angeles, California 90095

United States

UCLA-Hematology/Oncology_LA 2

Los Angeles, California 90095

United States

UCLA-Hematology/Oncology_LA

Los Angeles, California 90095

United States

Los Angeles Cancer Network_Pasadena

Pasadena, California 91105

United States

Los Angeles cancer Network_Riverside

Riverside, California 92501

United States

UC San Diego

San Diego, California 92037

United States

St. John's Cancer Center

Santa Monica, California 90404

United States

UCLA-Department of Medicine Hematology/Oncology-Parkside

Santa Monica, California 90404

United States

UCLA-Hetamtology/Oncology_S Monica

Santa Monica, California 90404

United States

Torrance Memorial Cancer Center

Torrance, California 90505

United States

Los Angeles Cancer Network_Valley Pres

Van Nuys, California 91405

United States

Cedars-Sinai Breast Health Services Building

West Hollywood, California 90048

United States

Smilow Cancer Hospital at Yale New Haven

New Haven, Connecticut 06511

United States

University of Miami _SCCC - Aventura

Aventura, Florida 33180

United States

University of Miami-SCCC-Lennar

Coral Gables, Florida 33146

United States

University of Miami_SCCC-Coral Springs

Coral Springs, Florida 33065

United States

University of Miami Hospital and Clinics - Deerfield Beach

Deerfield Beach, Florida 33442

United States

University of Miami_SCCC-Hollywood

Hollywood, Florida 33021

United States

Mayo Clinic Florida-Comprehensive Cancer Center

Jacksonville, Florida 32224

United States

University Of Miami-SCCC-Miami

Miami, Florida 33136

United States

University of Miami_SCCC - Kendall

Miami, Florida 33176

United States

Advent Health - Orlando

Orlando, Florida 32804

United States

University of Miami-SCCC-Plantation

Plantation, Florida 33324

United States

Winship Cancer Institute of Emory University

Atlanta, Georgia 30322

United States

Northwestern University

Chicago, Illinois 60611

United States

Southern Illinois University-Simmons

Springfield, Illinois 62702

United States

Carle Foundation Cancer Institute-Urbana

Urbana, Illinois 61801

United States

Northwest Cancer Center

Dyer, Indiana 46311

United States

AMR Kansas City Oncology

Kansas City, Kansas 66204

United States

Care Access-Marrero

Marrero, Louisiana 70072

United States

The Center for Cancer and Blood Disorders a division of American Oncology Partners, P.A.

Bethesda, Maryland 20817

United States

Mayo Clinic-Comprehensive Cancer Center-Breast Clinic

Rochester, Minnesota 55905

United States

Nebraska Cancer Specialists

Omaha, Nebraska 68130

United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire 03756

United States

Hunterdon Medical Center

Flemington, New Jersey 08822

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Babylon)

Babylon, New York 11702

United States

NYU Langone's Perlmutter Cancer Center

Manhattan, New York 10016

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(New Hyde Park)

New Hyde Park, New York 11042

United States

Manhattan Hematology /Oncology Associates

New York, New York 10016

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (NY)

New York, New York 10028

United States

New York Cancers & Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Patchogue)

Patchogue, New York 11772

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Port Jefferson Station2)

Port Jefferson Station, New York 11776

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(Port Jefferson Station1)

Port Jefferson Station, New York 11776

United States

New York Cancers & Blood Specialists

Port Jefferson Station, New York 11776

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Riverhead)

Riverhead, New York 11901

United States

New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Brox)

The Bronx, New York 10469

United States

Regional Medical Oncology Center_Wlson

Wilson, North Carolina 27893

United States

Gabrail Cancer & Research Center

Canton, Ohio 44718

United States

Cleveland Clinic

Cleveland, Ohio 44195

United States

Texas Oncology-Baylor Charles A. Sammons Cancer Center

Dallas, Texas 75246

United States

Mary Crowley Cancer Research

Dallas, Texas 75251

United States

DHR Health Oncology Institute

Edinburg, Texas 78539

United States

Texas Oncology - Fredericksburg

Fredericksburg, Texas 78624

United States

Texas Oncology - Harlingen

Harlingen, Texas 78550

United States

Texas Oncology McAllen

McAllen, Texas 78503

United States

Texas Oncology, New Braunfels

New Braunfels, Texas 78130

United States

Texas Oncology-San Antonio Cancer Care

San Antonio, Texas 78216

United States

Texas Oncology - San Antonio Northeast

San Antonio, Texas 78217

United States

Texas Oncology - San Antonio Stone Oak

San Antonio, Texas 78258

United States

Tranquil Clinical Research

Webster, Texas 77598

United States

Texas Oncology - Weslaco

Weslaco, Texas 78596

United States

Hematology-Oncology Associates of Fredericksburg, Inc

Fredericksburg, Virginia 22408

United States

Cancer Care Northwest-1 (601 S. Sherman)

Spokane, Washington 99202

United States

Cancer Care Northwest_2 (605 E. Holland)

Spokane, Washington 99218

United States

Cancer Care Northwest

Spokane Valley, Washington 99218

United States

Sheboygan Cancer & Blood Specialists

Sheboygan, Wisconsin 53081

United States