NCT06471673 · BriaCell Therapeutics Corporation
A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
What this study is about
This is an where both patients and doctors know the treatment given Phase 1/2a study. Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a clinically available check point inhibitor (CPI).
View original scientific description
This is an open-label Phase 1/2a study. Once the safety of the BC1 cell line alone has been demonstrated in Phase 1, in Phase 2, patients will be treated with the Bria-OTS regimen (see below) and a clinically available check point inhibitor (CPI). During the monotherapy phase of Phase 1, one patient will be treated intradermally every 2 weeks for 6 weeks (4 doses) with an initial dose of the BC1 cell line. If this dose is tolerated, the next patient will receive an increased dose of BC1. If once again tolerated, the third patient will receive a further dose increase of the BC1. Once at least 3 patients have been safely treated with the BC1 cell line, with no dose-limiting toxicity (DLT), the combinational phase of the study will commence. Following the monotherapy phase, patients will be treated with BC1 and the Bria-OTS regimen (see below) every 3 weeks, plus a CPI at the FDA approved labelled dose and schedule. There will be at least a 2-week spacing between enrollment of each of the first three subjects in the study in order to assess for any early unanticipated risk(s). During the Phase 1 combination and Phase 2 expansion phases, all patients will be treated with BC1 cells as part of the Bria-OTS regimen, which includes cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell inoculation, and peginterferon alpha-2a administered on the same day, following BC1 cell inoculation.
Interventions
BIOLOGICAL
BC1 cell line
BC1 cell line is a different experimental, HER-2 positive, allogeneic, whole cell BC cell lines designed to secrete GM-CSF in situ and augment dendritic cell activity. Similar to the SV-BR-1-GM cell line (NCT03328026, IND 10312), the BC cell line is derived from the BC parent cell line, SV-BR-1, which expresses multiple tumor associated antigens (TAAs)
BIOLOGICAL
Bria-OTS regimen and CPI (tislelizumab)
Biological: BC1 * BC1 inoculation intradermally at 4 sites Drug: Low dose cyclophosphamide * Pretreatment with low dose cyclophosphamide 2-3 days prior to BC1 inoculation Drug: Interferon * Subjects will receive low dose peginterferon alpha-2a on the same day as cell inoculation. Drug: Tislelizumab * CPI treatment will also be given on the same day as cell inoculation.
BIOLOGICAL
Bria-OTS regimen and CPI (tislelizumab) expansion cohort
Biological: BC1 * BC1 inoculation intradermally at 4 sites Drug: Low dose cyclophosphamide * Pretreatment with low dose cyclophosphamide 2-3 days prior to BC1 inoculation Drug: Interferon * Subjects will receive low dose peginterferon alpha-2a on the same day as cell inoculation. Drug: Tislelizumab * CPI treatment will also be given on the same day as cell inoculation.
Primary outcome measures
Safety as assessed by adverse events (AEs), including serious adverse events (SAEs)
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
Total number of AEs
Evaluate the Proportion of Patients with Abnormalities in Safety Laboratory Parameters that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab)
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters
Evaluate changes in the electrocardiogram QT interval that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab). [Safety]
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o Electrocardiograms (ECG) with measurement of the QT interval
Evaluate the proportion of patients with abnormal physical examination findings including vital signs
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
To evaluate the safety of BC1 as assessed by: o The Proportion of Patients with Abnormalities in Physical Examination Findings and Abnormal Vital Signs
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
Inclusion criteria
- Histological confirmed recurrent metastatic breast cancer which has failed prior therapy defined as:
- Human epidermal growth factor 2 (EGFR2, HER2) positive tumors must have failed therapy with at least 2 anti-HER2 agents
- HER2 negative and either ER or PR positive tumors: must be refractory to hormonal therapy and previously treated with at least 2 hormone based targeted therapy containing regimens.
- Triple-negative and inflammatory tumors must have exhausted other curative intent therapies including prior treatment with a taxane and platinum-based agent
- All other MBC types must have exhausted other curative intent therapies including any genomic or germline directed targeted therapy having available approved drug(s)
- Patients with new or progressive breast cancer metastatic to the brain will be eligible, provided: i. The brain metastases must be clinically stable (without evidence of progressive disease by imaging) for at least 4 weeks, prior to first dose. ii. There is no need for steroids and patients have not had steroids for at least 2 weeks prior to the first dose.
- Be 18 years of age or older.
- Have expected survival of at least 4 months.
- Have adequate performance status (up to and including ECOG 2)
- Patients must be stable with all known or expected toxicities from previous treatment including:
- Prior immune related toxicity must not have exceeded Grade 2 with exception of stable endocrinopathy (endocrinopathy if well-managed, is not
Exclusion criteria
- Toxicity of prior therapy that has not recovered to ≤ grade 1 or baseline (with the exception of any grade of alopecia, adequately treated endocrinopathy, and anemia not requiring transfusion support). Exclusion Criteria:
- Concurrent anti-cancer treatment.
- Recent chemotherapy, radiotherapy, or other anti-cancer treatment within 3 weeks of first protocol treatment.
- Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug.
- History of clinical hypersensitivity to the designated therapy, as specified in the protocol or to any components used in the preparation of any cell line in this study.
- History of clinical hypersensitivity to any protocol specified therapy.
- BUN \>30 in conjunction with a creatinine \>2, or calculated creatinine clearance (CrCl) \<30 mL/min (GFR can be used in place of creatinine or CrCl).
- Absolute granulocyte count \< 1000; platelets \<50,000.
- Bilirubin \>2.0; alkaline phosphatase \>4x upper limit of normal (ULN); ALT/AST \>2x ULN. For patients with hepatic metastases, ALT/AST \>5x ULN is exclusionary.
- Proteinuria \>1+ on urinalysis or \>1 gm/24hr.
- New York Heart Association stage 3 or 4 cardiac disease.
- A pleural or pericardial effusion of moderate severity or worse.
- 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.
- Men who are fertile/reproductively competent, should take appropriate precautions to avoid fathering a child for the duration of the study.
- Women who are pregnant or nursing.
- Patients with concurrent second malignancy.
- Persons with previous malignancies requiring treatment within the past 24 months.
- Patients who have clinical or laboratory features indicative of AIDS and are HIV positive (by self-report).
- 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 21 days prior to first dose of study treatment.
- Patients who are on treatment for an autoimmune disease, unless specifically approved by the Investigator and the Sponsor.
- Patients with severe psychiatric (e.g., schizophrenia, bipolar, or borderline personality disorder) or other clinically progressive major medical problems, unless approved by the Investigator and Sponsor.
- Patients may not be on a concurrent clinical trial, unless approved by Investigator and Sponsor.
Where
- Santa Monica, California
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Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced Aug 26, 2024 · Source of record for eligibility and locations