A Study of BRIA-OTS Cellular Immunotherapy in Metastatic Recurrent Breast Cancer
NCT Number: NCT06471673
Status: RECRUITING
Study Type: INTERVENTIONAL
Phases: PHASE1|PHASE2
Conditions: Breast Cancer|Breast Tumor|Cancer of Breast|Cancer of the Breast|Malignant Tumor of Breast|Tumors, Breast
Interventions: BIOLOGICAL: BC1 cell line|BIOLOGICAL: Bria-OTS regimen and CPI (tislelizumab)|BIOLOGICAL: Bria-OTS regimen and CPI (tislelizumab) expansion cohort
Sponsor: BriaCell Therapeutics Corporation
Sex: ALL
Age: ADULT, OLDER_ADULT
Enrollment: 18
Study Design: Allocation: NON_RANDOMIZED|Intervention Model: SEQUENTIAL|Masking: NONE|Primary Purpose: TREATMENT
Start Date: 2024-05-29
Completion Date: 2025-10-30
Locations: Sarcoma Oncology Center, Santa Monica, California, 90403, United States

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).

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.

Primary Outcome Measures: Safety as assessed by adverse events (AEs), including serious adverse events (SAEs), Total number of AEs, 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:

o The Proportion of Patients with Abnormalities in Safety Laboratory Parameters, 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:

o Electrocardiograms (ECG) with measurement of the QT interval, 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:

o The Proportion of Patients with Abnormalities in Physical Examination Findings and Abnormal Vital Signs, Throughout study period plus 4 weeks, approximately 16 weeks total
Secondary Outcome Measures: 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, 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, 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, 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, Throughout study period plus 4 weeks, approximately 16 weeks total
Other Outcome Measures: PFS and OS treated with HLA-characterized cellular immunotherapy, To evaluate the effect of the BC1 on progression-free survival (PFS)

• To assess the single agent activity of the BC1 regimen in the sample cohort using PFS, ORR, and CBR, and changes in circulating tumor cells before and after therapy., Throughout study period plus 4 weeks, approximately 16 weeks total|Evaluate Immune Responses, Immune responses will be evaluated by known and hypothesized covariates including DTH, Throughout study period plus 4 weeks, approximately 16 weeks total|Stratified Analysis of Outcomes by HLA type, Determine specific HLA type for analysis, Throughout study period plus 4 weeks, approximately 16 weeks total|Stratified Analysis of Outcomes by Tumor Grade, Classify the tumor based on its differentiation:

* well-differentiated or Grade 1
* moderately differentiated or Grade 2
* poorly differentiated or Grade 3, Throughout study period plus 4 weeks, approximately 16 weeks total|Stratified analysis of Circulating Cancer cell or Cancer-associated cell expression of PD-L1, PD-L2, and other selected antigens such as the cancer/testis antigen PRAME, Measure the expression relevant antigens on circulating cancer cells or cancer-associated cells, which may predict response to immunotherapy., Throughout study period plus 4 weeks, approximately 16 weeks total|Second Progression-Free Survival (PFS2) on subsequent therapy, Evaluate effectiveness of subsequent therapy in delaying further progression from the time of randomization to the second disease progression or death from any cause., Throughout study period plus 4 weeks, approximately 16 weeks total