Breast CancerPhase 1/2NCT06471673
A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
A Phase 1/2 study testing BC1 cell line, Bria-OTS regimen and CPI (tislelizumab) and Bria-OTS regimen and CPI (tislelizumab) expansion cohort in people with Breast Cancer and Breast Tumor, run by BriaCell Therapeutics Corporation at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer, Breast Tumor, Cancer of Breast
- What is being tested?
- BC1 cell line, Bria-OTS regimen and CPI (tislelizumab) and Bria-OTS regimen and CPI (tislelizumab) expansion cohort
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 29 May 2024to 30 Oct 2025
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
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- 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.
- 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 exclusionary).
- 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).
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Sarcoma Oncology Center
Santa Monica, California, 90403
Victoria Chua-Alcala, MD, 310-552-9999, vchua@sarcomaoncology.com
Sant Chawla, MD, 310-552-9999, santchawla@sarcomaoncology.com
About this study
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.
Read more
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.
Read the detailed description
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 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 cells. If once again tolerated, the third patient will receive a further increased dose of 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.
Imaging studies will be performed at screening for baseline prior to first treatment; after the completion of the monotherapy phase just before starting the combination phase, and subsequently every 9 weeks for the first 6 months then q12 weeks thereafter while on treatment.
Patients who develop progressive disease on imaging, may remain on treatment as long as the Investigator feels they are deriving clinical benefit and there is no reasonable, meaningful, clinical alternative therapy available. Subjects will continue to be followed for time on subsequent therapy (PFS2) and survival by phone call or medical record review, every 3 months for up to 2 years.
Study Drug, Dosage, and Mode of Administration:
The Part 1 monotherapy phase of Phase 1 will proceed as follows for each patient:
Subject 1, Q2w for 4 doses Subject 2, Q2w for 4 doses Subject 3, Q2w for 4 doses
Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment.
If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. If none of the patients in the expanded cohort experience a DLT (DLT rate of 1/4), the study will move into Bria-OTS and CPI combination. The dose for the combination will be either the highest dose at which no DLT is observed among the first 3 patients or the 3 patient expanded cohort dose level. In Phase 1, DLTs for determining the combinational BC1 dose will be observed until the first scheduled assessment. If the Phase 1 DLT rate is ≥ 2/4, an additional 3 patients will be dosed using the next lower dose level or 10 million cells (whichever is higher). If none of the 3 subjects experience dose-limiting toxicities (DLTs), that determined BC1 MTD dose will be included in the Part 2 combinational phase of Phase 1 along with a CPI. If a tolerated dose for BC1 cell line cannot be identified, further investigation will be paused, the data reviewed and may resume at a lower dose only with protocol amendment and IRB approval.
Following the Phase 1, Part 1 monotherapy phase, 3 patients will be treated every 3 weeks with the Bria-OTS regimen with a CPI in the Part 2 combination phase. The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI on the same day of the cell inoculation according to approved dosing.
Once 3 patients have been safely treated with the Bria-OTS regimen and CPI for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI).
- Conditions
- Breast Cancer, Breast Tumor, Cancer of Breast, Cancer of the Breast, Malignant Tumor of Breast, Tumors, Breast
- Being tested
- BC1 cell line, Bria-OTS regimen and CPI (tislelizumab), Bria-OTS regimen and CPI (tislelizumab) expansion cohort
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BC1 cell lineBiological
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)
Bria-OTS regimen and CPI (tislelizumab)Biological
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.
Bria-OTS regimen and CPI (tislelizumab) expansion cohortBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Phase 1, Part 1 Monotherapy Phase | Experimental | Subject 1, Q2w for 4 doses
Subject 2, Q2w for 4 doses
Subject 3, Q2w for 4 doses Treatment is administered every 2 weeks for a total of 4 doses.
Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment.
If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. A total of 3-6 subjects will be assessed for safety. Receives: Biological: BC1 cell line |
| Phase 1, Part 2 Combination Phase | Experimental | 3 subjects will be treated every 3 weeks with the Bria-OTS regimen with a CPI (tislelizumab) in the Part 2 combination phase.
The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing.
Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab). Receives: Biological: Bria-OTS regimen and CPI (tislelizumab) |
| Phase 2 Expansion Cohort | Experimental | Once 3 patients have been safely treated with the Bria-OTS regimen and CPI (tislelizumab) for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI).
The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing.
Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab). Receives: Biological: Bria-OTS regimen and CPI (tislelizumab) expansion cohort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety as assessed by adverse events (AEs), including serious adverse events (SAEs)
Total number of AEs
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
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)
To evaluate the safety of BC1 as assessed by:
- The Proportion of Patients with Abnormalities in Safety Laboratory Parameters
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Evaluate changes in the electrocardiogram QT interval that occur in patients treated with BC1 and BC1 administered in combination with CPI (tislelizumab). [Safety]
To evaluate the safety of BC1 as assessed by:
- Electrocardiograms (ECG) with measurement of the QT interval
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Evaluate the proportion of patients with abnormal physical examination findings including vital signs
To evaluate the safety of BC1 as assessed by:
- The Proportion of Patients with Abnormalities in Physical Examination Findings and Abnormal Vital Signs
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Secondary outcomes (4)
Tumor response as assessed by Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Quantify tumor ORR
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Clinical response rate as determined by local standard of care imaging and investigators
Determine clinical relevance of tumor response
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Non-progressive rate (aka: clinical benefit rate), defined as CR, PR, or stable disease (SD) per RECIST 1.1 and as determined by local standard of care imaging and investigators
Quantify change in tumor rate of progression
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Duration of response (DoR)
Quantify tumor duration of response to therapy
Measured: Throughout study period plus 4 weeks, approximately 16 weeks total
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jun 2024
- Study start29 May 2024
- Primary completion30 Apr 2025 (estimated)
- Study completion30 Oct 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (91)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- BriaCell Therapeutics Corporation
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Giuseppe Del Priore, MD, MPH, Study chair, BriaCell Therapeutics CorpVictoria Chua-Alcala, MD, Study director, Sarcoma Oncology Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06471673
- Sponsor's protocol ID
- BC-OTS-001
- Status last verified
- Aug 2024
- First submitted
- 11 Jun 2024
- Last updated
- 26 Aug 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Ahn SS, Irie RF, Weisenburger TH, Jones PC, Juillard G, Roe DJ, Morton DL. Humoral immune response to intralymphatic immunotherapy for disseminated melanoma: correlation with clinical response. Surgery. 1982 Aug;92(2):362-7.
PubMed 7101129Al-Awadhi A, Lee Murray J, Ibrahim NK. Developing anti-HER2 vaccines: Breast cancer experience. Int J Cancer. 2018 Nov 1;143(9):2126-2132. doi: 10.1002/ijc.31551. Epub 2018 May 10.
PubMed 29693245Antonarelli G, Corti C, Tarantino P, Ascione L, Cortes J, Romero P, Mittendorf EA, Disis ML, Curigliano G. Therapeutic cancer vaccines revamping: technology advancements and pitfalls. Ann Oncol. 2021 Dec;32(12):1537-1551. doi: 10.1016/j.annonc.2021.08.2153. Epub 2021 Sep 6.
PubMed 34500046Arico E, Belardelli F. Interferon-alpha as antiviral and antitumor vaccine adjuvants: mechanisms of action and response signature. J Interferon Cytokine Res. 2012 Jun;32(6):235-47. doi: 10.1089/jir.2011.0077. Epub 2012 Apr 10.
PubMed 22490303Avigan D, Vasir B, Gong J, Borges V, Wu Z, Uhl L, Atkins M, Mier J, McDermott D, Smith T, Giallambardo N, Stone C, Schadt K, Dolgoff J, Tetreault JC, Villarroel M, Kufe D. Fusion cell vaccination of patients with metastatic breast and renal cancer induces immunological and clinical responses. Clin Cancer Res. 2004 Jul 15;10(14):4699-708. doi: 10.1158/1078-0432.CCR-04-0347.
PubMed 15269142Baars A, Claessen AM, van den Eertwegh AJ, Gall HE, Stam AG, Meijer S, Giaccone G, Meijer CJ, Scheper RJ, Wagstaff J, Vermorken JB, Pinedo HM. Skin tests predict survival after autologous tumor cell vaccination in metastatic melanoma: experience in 81 patients. Ann Oncol. 2000 Aug;11(8):965-70. doi: 10.1023/a:1008363601515.
PubMed 11038032Baker F, Haffer SC, Denniston M. Health-related quality of life of cancer and noncancer patients in Medicare managed care. Cancer. 2003 Feb 1;97(3):674-81. doi: 10.1002/cncr.11085.
PubMed 12548610Berd D, Maguire HC Jr, Mastrangelo MJ. Induction of cell-mediated immunity to autologous melanoma cells and regression of metastases after treatment with a melanoma cell vaccine preceded by cyclophosphamide. Cancer Res. 1986 May;46(5):2572-7.
PubMed 3697996Berd D, Mastrangelo MJ. Effect of low dose cyclophosphamide on the immune system of cancer patients: reduction of T-suppressor function without depletion of the CD8+ subset. Cancer Res. 1987 Jun 15;47(12):3317-21.
PubMed 2953413Boyer CM, Dawson DV, Neal SE, Winchell LF, Leslie DS, Ring D, Bast RC Jr. Differential induction by interferons of major histocompatibility complex-encoded and non-major histocompatibility complex-encoded antigens in human breast and ovarian carcinoma cell lines. Cancer Res. 1989 Jun 1;49(11):2928-34.
PubMed 2497969Brahmer JR, Lacchetti C, Schneider BJ, Atkins MB, Brassil KJ, Caterino JM, Chau I, Ernstoff MS, Gardner JM, Ginex P, Hallmeyer S, Holter Chakrabarty J, Leighl NB, Mammen JS, McDermott DF, Naing A, Nastoupil LJ, Phillips T, Porter LD, Puzanov I, Reichner CA, Santomasso BD, Seigel C, Spira A, Suarez-Almazor ME, Wang Y, Weber JS, Wolchok JD, Thompson JA; National Comprehensive Cancer Network. Management of Immune-Related Adverse Events in Patients Treated With Immune Checkpoint Inhibitor Therapy: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2018 Jun 10;36(17):1714-1768. doi: 10.1200/JCO.2017.77.6385. Epub 2018 Feb 14.
PubMed 29442540Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12.
PubMed 30207593Brinkmann U, Kontermann RE. The making of bispecific antibodies. MAbs. 2017 Feb/Mar;9(2):182-212. doi: 10.1080/19420862.2016.1268307.
PubMed 28071970Callard RE, Smith SH, Shields JG, Levinsky RJ. T cell help in human antigen-specific antibody responses can be replaced by interleukin 2. Eur J Immunol. 1986 Sep;16(9):1037-42. doi: 10.1002/eji.1830160902.
PubMed 3019704Carson WE 3rd, Unger JM, Sosman JA, Flaherty LE, Tuthill RJ, Porter MJ, Thompson JA, Kempf RA, Othus M, Ribas A, Sondak VK. Adjuvant vaccine immunotherapy of resected, clinically node-negative melanoma: long-term outcome and impact of HLA class I antigen expression on overall survival. Cancer Immunol Res. 2014 Oct;2(10):981-7. doi: 10.1158/2326-6066.CIR-14-0052. Epub 2014 Jul 3.
PubMed 24994597
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
- ClinicalTrials.gov ID
- NCT06471673
- Acronym / sponsor ID
- BC-OTS-001
- Conditions
- Breast Cancer, Breast Tumor, Cancer of Breast, Cancer of the Breast, Malignant Tumor of Breast, Tumors, Breast
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- BriaCell Therapeutics CorporationIndustry (pharma, biotech, devices)
- Study start
- 29 May 2024 (actual)
- Primary completion
- 30 Apr 2025 (estimated)
- Study completion
- 30 Oct 2025 (estimated)
- First posted
- 24 Jun 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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 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 cells. If once again tolerated, the third patient will receive a further increased dose of 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.
Imaging studies will be performed at screening for baseline prior to first treatment; after the completion of the monotherapy phase just before starting the combination phase, and subsequently every 9 weeks for the first 6 months then q12 weeks thereafter while on treatment.
Patients who develop progressive disease on imaging, may remain on treatment as long as the Investigator feels they are deriving clinical benefit and there is no reasonable, meaningful, clinical alternative therapy available. Subjects will continue to be followed for time on subsequent therapy (PFS2) and survival by phone call or medical record review, every 3 months for up to 2 years.
Study Drug, Dosage, and Mode of Administration:
The Part 1 monotherapy phase of Phase 1 will proceed as follows for each patient:
Subject 1, Q2w for 4 doses Subject 2, Q2w for 4 doses Subject 3, Q2w for 4 doses
Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment.
If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. If none of the patients in the expanded cohort experience a DLT (DLT rate of 1/4), the study will move into Bria-OTS and CPI combination. The dose for the combination will be either the highest dose at which no DLT is observed among the first 3 patients or the 3 patient expanded cohort dose level. In Phase 1, DLTs for determining the combinational BC1 dose will be observed until the first scheduled assessment. If the Phase 1 DLT rate is ≥ 2/4, an additional 3 patients will be dosed using the next lower dose level or 10 million cells (whichever is higher). If none of the 3 subjects experience dose-limiting toxicities (DLTs), that determined BC1 MTD dose will be included in the Part 2 combinational phase of Phase 1 along with a CPI. If a tolerated dose for BC1 cell line cannot be identified, further investigation will be paused, the data reviewed and may resume at a lower dose only with protocol amendment and IRB approval.
Following the Phase 1, Part 1 monotherapy phase, 3 patients will be treated every 3 weeks with the Bria-OTS regimen with a CPI in the Part 2 combination phase. The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI on the same day of the cell inoculation according to approved dosing.
Once 3 patients have been safely treated with the Bria-OTS regimen and CPI for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI).
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Phase 1, Part 1 Monotherapy Phase | Experimental | Biological: BC1 cell lineSubject 1, Q2w for 4 doses Subject 2, Q2w for 4 doses Subject 3, Q2w for 4 doses Treatment is administered every 2 weeks for a total of 4 doses. Initially, safety will be assessed on these 3 subjects. DLTs are defined as CTCAE Grade 3 or 4 adverse events that are suspected to be possibly related to study treatment. If 1 of 3 Phase 1 subjects experience a DLT, that dose cohort will be expanded to another 3 patients before the combinational phase begins. A total of 3-6 subjects will be assessed for safety. |
| Phase 1, Part 2 Combination Phase | Experimental | Biological: Bria-OTS regimen and CPI (tislelizumab)3 subjects will be treated every 3 weeks with the Bria-OTS regimen with a CPI (tislelizumab) in the Part 2 combination phase. The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing. Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab). |
| Phase 2 Expansion Cohort | Experimental | Biological: Bria-OTS regimen and CPI (tislelizumab) expansion cohortOnce 3 patients have been safely treated with the Bria-OTS regimen and CPI (tislelizumab) for 2 cycles, Phase 2 will enroll an expansion cohort, consisting of up to an additional 9 subjects (for a total of 12 treated with the Bria-OTS regimen and CPI). The Bria-OTS regimen consists of cyclophosphamide 300 mg/m2 2-3 days prior to BC1 cell line inoculation. On the same day as the cell inoculation, subjects will receive peginterferon alpha-2a. Subjects will also receive the CPI (tislelizumab) on the same day of the cell inoculation according to approved dosing. Treatment is administered every 3 weeks in combination with the Bria-OTS regimen and CPI (tislelizumab). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Histological confirmed recurrent metastatic breast cancer which has failed prior
- 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:
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BC1 cell lineBC1 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 | Phase 1, Part 1 Monotherapy Phase |
| 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 | Phase 1, Part 2 Combination Phase |
| Bria-OTS regimen and CPI (tislelizumab) expansion cohortBiological: 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 | Phase 2 Expansion Cohort |
Primary outcome
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
4 secondary outcomes
Tumor response as assessed by Objective response rate (ORR), defined as complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Clinical response rate as determined by local standard of care imaging and investigators
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Non-progressive rate (aka: clinical benefit rate), defined as CR, PR, or stable disease (SD) per RECIST 1.1 and as determined by local standard of care imaging and investigators
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
Tumor response as assessed by Duration of response (DoR)
Time frame: Throughout study period plus 4 weeks, approximately 16 weeks total
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2024.
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- Cyclophosphamide Prescribing Information.Link provided by the sponsor.
- NCCN Clinical Practice Guidelines in Oncology.Link provided by the sponsor.
- SEER Cancer Stat Facts: Female Breast Cancer. National Cancer Institute. Bethesda, MD,Link provided by the sponsor.
- CTCAE v5.0 Toxicity Criteria:Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Giuseppe Del Priore, MD, MPH study chair
BriaCell Therapeutics Corp
Victoria Chua-Alcala, MD study director
Sarcoma Oncology Research Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing BC1 cell line, Bria-OTS regimen and CPI (tislelizumab) and Bria-OTS regimen and CPI (tislelizumab) expansion cohort in people with Breast Cancer and Breast Tumor, run by BriaCell Therapeutics Corporation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 26 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tamar Aghajanian, PharmD (1-888-485-6340, tamar@briacell.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety as assessed by adverse events (AEs), including serious adverse events (SAEs) (time frame: Throughout study period plus 4 weeks, approximately 16 weeks total). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06471673, which also lists 91 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2024.