Randomized, Open-Label Study of the Bria-IMT Regimen and Check Point Inhibitor vs Physicians' Choice in Advanced Metastatic Breast Cancer.

Plain English Summary

Study of the Bria-IMT Regimen and CPI vs Physicians' Choice in Advanced Metastatic Breast Cancer. is a Phase 3 clinical trial sponsored by BriaCell Therapeutics Corporation studying Breast Cancer, Metastatic Breast Cancer, Breast Neoplasm, Breast Cancer Metastatic, End Stage Cancer. This trial tests a new treatment called Bria-IMT combined with a checkpoint inhibitor against the standard treatment chosen by doctors. It is for adults with advanced, widespread breast cancer that has not responded to other treatments. Participants will receive either the new combination therapy or the doctor's choice of treatment, and will be monitored for survival and other outcomes. Alternative treatments include various chemotherapy and hormone therapies, depending on the specific type of breast cancer. The trial aims to enroll 404 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults aged 18 and older with a confirmed diagnosis of breast cancer that has spread or returned and cannot be treated locally. Patients must have tried and failed previous treatments specific to their cancer type (e.g., HER2-positive, ER/PR-positive, triple-negative, or HER2-low). Patients with brain metastases may be eligible if they are stable and not requiring steroids. Individuals with certain blood count, liver, or kidney function abnormalities, or significant heart conditions may not be eligible. This trial is studying Breast Cancer, Metastatic Breast Cancer, Breast Neoplasm, Breast Cancer Metastatic, End Stage Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary goal is to see if the new treatment helps patients live longer compared to the standard treatment. The specific primary outcome measures are: Overall Survival (Up to 60 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for new therapies in patients with advanced metastatic breast cancer who have exhausted all other treatment options, aiming to improve survival. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Cancer, Metastatic Breast Cancer, Breast Neoplasm, Breast Cancer Metastatic, End Stage Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a significant unmet need in late-stage breast cancer, with potential for a novel immunotherapy combination if successful, indicating a promising market opportunity for BriaCell Ther Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage.

Is This Trial Right for Me?

Ask your doctor if your specific type of breast cancer has been treated with all available options. Understand that you will be randomly assigned to one of two treatment groups. Participation involves regular clinic visits for treatment, monitoring, and tests over several years. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 404 participants

Interventions

• BIOLOGICAL: SV-BR-1-GM — 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
• DRUG: Cyclophosphamide — 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.
• DRUG: Interferon infiltration of the inoculation site — 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.
• DRUG: Retifanlimab — 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.
• DRUG: Treatment of Physician's Choice — 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.

Primary Outcomes

• Overall Survival (Up to 60 months)

Secondary Outcomes

• Progression-free survival (PFS) (Up to 60 months)
• Clinical Benefit Rate (CBR) (Up to 60 months)
• Overall response rate (ORR) (Up to 60 months)
• Quality of life (QoL) (Up to 60 months)
• CNS Event free survival (EFS) (Up to 60 months)

Full 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 neg

Trial Locations

• Mayo Clinic-Comprehensive Cancer Center-Breast Clinic, Phoenix, Arizona, United States
• University of Arizona-Cancer Center, Tucson, Arizona, United States
• Los Angeles cancer Network_Anaheim, Anaheim, California, United States
• Comprehensive Blood and Cancer Center, Bakersfield, California, United States
• Cedars-Sinai Cancer Beverly Hills, Beverly Hills, California, United States
• Los Angeles Cancer Network_Corona, Corona, California, United States
• Los Angeles cancer Network_Fountain Vallley, Fountain Valley, California, United States
• Los Angeles Cancer Network_Glendale, Glendale, California, United States
• Hoag Hospital Center, Irvine, California, United States
• Hoag Hospital Irvine, Irvine, California, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Metastatic Breast Cancer
• Advanced Breast Cancer
• Triple-Negative Breast Cancer
• HER2-Positive Breast Cancer
• Hormone Receptor-Positive Breast Cancer
• HER2-Low Breast Cancer
• Metastatic Cancer
• Cancer
• Oncology

More Breast Cancer Trials

View all Breast Cancer clinical trials