Overview
Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer.
Status:
Recruiting
Recruiting
Trial end date:
2025-12-01
2025-12-01
Target enrollment:
0
0
Participant gender:
All
All
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.Phase:
Phase 3Accepts Healthy Volunteers?
NoDetails
Lead Sponsor:
BriaCell Therapeutics CorporationTreatments:
Cyclophosphamide
Interferons
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.