Clinical trial NCT06072612: Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer.
Official title: Randomized, Open-Label Study of the Bria-IMT Regimen and Check Point Inhibitor vs Physicians' Choice in Advanced Metastatic Breast Cancer.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Breast Cancer
Metastatic Breast Cancer
Breast Neoplasm
Breast Cancer Metastatic
End Stage Cancer
Keywords: Breast
metastatic
advanced
cancer
late line
Lead sponsor: BriaCell Therapeutics Corporation
Sponsor class: INDUSTRY
First posted: 2023-10-10
Enrollment: 404
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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: 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.

Primary outcomes:
measure: Overall Survival
timeFrame: Up to 60 months
Secondary outcomes:
measure: Progression-free survival (PFS)
timeFrame: Up to 60 months
measure: Clinical Benefit Rate (CBR)
timeFrame: Up to 60 months
measure: Overall response rate (ORR)
timeFrame: Up to 60 months
measure: Quality of life (QoL)
timeFrame: Up to 60 months
measure: CNS Event free survival (EFS)
timeFrame: Up to 60 months
Other outcomes:
Locations:
city: Tucson
country: United States
facility: University of Arizona-Cancer Center
state: Arizona
city: Anaheim
country: United States
facility: Los Angeles cancer Network_Anaheim
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Corona
country: United States
facility: Los Angeles Cancer Network_Corona
state: California
city: Fountain Valley
country: United States
facility: Los Angeles cancer Network_Fountain Vallley
state: California
city: Glendale
country: United States
facility: Los Angeles Cancer Network_Glendale
state: California
city: Irvine
country: United States
facility: Hoag Hospital Center
state: California
city: Irvine
country: United States
facility: Hoag Hospital Irvine
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network
state: California
city: Los Angeles
country: United States
facility: Los Angeles Cancer Network_Century City
state: California
city: Pasadena
country: United States
facility: Los Angeles Cancer Network_Pasadena
state: California
city: Riverside
country: United States
facility: Los Angeles cancer Network_Riverside
state: California
city: San Diego
country: United States
facility: UC San Diego
state: California
city: Santa Monica
country: United States
facility: St. John's Cancer Center
state: California
city: Torrance
country: United States
facility: Torrance Memorial Cancer Center
state: California
city: Van Nuys
country: United States
facility: Los Angeles Cancer Network_Valley Pres
state: California
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Coral Gables
country: United States
facility: University of Miami-SCCC-Lennar
state: Florida
city: Miami
country: United States
facility: University Of Miami-SCCC-Miami
state: Florida
city: Orlando
country: United States
facility: Advent Health - Orlando
state: Florida
city: Plantation
country: United States
facility: University of Miami-SCCC-Plantation
state: Florida
city: Chicago
country: United States
facility: Northwestern University
state: Illinois
city: Springfield
country: United States
facility: Southern Illinois University-Simmons
state: Illinois
city: Urbana
country: United States
facility: Carle Foundation Cancer Institute-Urbana
state: Illinois
city: Dyer
country: United States
facility: Northwest Cancer Center
state: Indiana
city: Kansas City
country: United States
facility: AMR Kansas City Oncology
state: Kansas
city: Marrero
country: United States
facility: Care Access-Marrero
state: Louisiana
city: Bethesda
country: United States
facility: The Center for Cancer and Blood Disorders a division of American Oncology Partners, P.A.
state: Maryland
city: Omaha
country: United States
facility: Nebraska Cancer Specialists
state: Nebraska
city: Babylon
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Babylon)
state: New York
city: Bronx
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Brox)
state: New York
city: New Hyde Park
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(New Hyde Park)
state: New York
city: New York
country: United States
facility: Manhattan Hematology /Oncology Associates
state: New York
city: New York
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C (NY)
state: New York
city: Patchogue
country: United States
facility: New York Cancers & Blood Specialists_North Shore Hematology Oncology Assocaites P.C (Patchogue)
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Port Jefferson Station2)
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C.(Port Jefferson Station1)
state: New York
city: Port Jefferson Station
country: United States
facility: New York Cancers & Blood Specialists
state: New York
city: Riverhead
country: United States
facility: New York Cancer and Blood Specialists_North Shore Hematology Oncology Assocaites P.C. (Riverhead)
state: New York
city: Canton
country: United States
facility: Gabrail Cancer & Research Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Dallas
country: United States
facility: Texas Oncology-Baylor Charles A. Sammons Cancer Center
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research
state: Texas
city: Edinburg
country: United States
facility: DHR Health Oncology Institute
state: Texas
city: Fredericksburg
country: United States
facility: Texas Oncology - Fredericksburg
state: Texas
city: Harlingen
country: United States
facility: Texas Oncology - Harlingen
state: Texas
city: McAllen
country: United States
facility: Texas Oncology McAllen
state: Texas
city: New Braunfels
country: United States
facility: Texas Oncology, New Braunfels
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology-San Antonio Cancer Care
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Northeast
state: Texas
city: San Antonio
country: United States
facility: Texas Oncology - San Antonio Stone Oak
state: Texas
city: Webster
country: United States
facility: Tranquil Clinical Research
state: Texas
city: Weslaco
country: United States
facility: Texas Oncology - Weslaco
state: Texas
city: Fredericksburg
country: United States
facility: Hematology-Oncology Associates of Fredericksburg, Inc
state: Virginia
city: Spokane Valley
country: United States
facility: Cancer Care Northwest
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest-1 (601 S. Sherman)
state: Washington
city: Spokane
country: United States
facility: Cancer Care Northwest_2 (605 E. Holland)
state: Washington
city: Sheboygan
country: United States
facility: Sheboygan Cancer & Blood Specialists
state: Wisconsin
Study officials:
affiliation: BriaCell Therapeutics
name: Giuseppe Del Priore, MD MPH
role: STUDY_DIRECTOR
References: