This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC).
This is a Phase II, randomized, open-label trial to evaluate the clinical and immunologic activity of pembrolizumab plus chemotherapy when combined with various immunotherapy induction regimens as neoadjuvant therapy for triple negative breast cancer (TNBC). A commonly used standard neoadjuvant regimen for TNBC is a weekly taxane (e.g., paclitaxel 80mg/m2) for 12 weeks followed by an anthracycline (e.g., doxorubicin 60 mg/m2 plus cyclophosphamide at 600 mg/m2 \[AC\]) every 3 weeks (Q3W) for 4 cycles. The chemotherapy regimen included in this study is built upon the aforementioned regimen. Pembrolizumab in combination with this regimen will be studied as part of a multi-arm study that randomizes subjects to receive: * Control Arm: (Pembro + ACT): Pembrolizumab induction (single-dose 200mg IV), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. * Arm A: (Pembro + IRX-2 + ACT): Pembrolizumab (single-dose 200mg IV) + cyclophosphamide (single-dose 300 mg/m2 IV) + IRX-2 induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab Q3W + paclitaxel (T) weekly x 4 cycles, followed by IRX-2 re-induction (1mL SQ x 2 daily, x 10 days), followed by pembrolizumab + doxorubicin + cyclophosphamide (AC) Q3W x 4 cycles as neoadjuvant therapy prior to surgery. * Subsequent induction therapy arms are to be included in protocol amendments. Note: 1 cycle = 21 days
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
Pembrolizumab is a humanized anti-PD-1 mAb of the IgG4/kappa isotype with a stabilizing S228P sequence alteration in the Fc region.
IRX-2, is a cell-derived biologic with multiple active cytokine components that acts on multiple cell types of the immune system including T cells, dendritic cells and natural killer cells.
Providence Portland Medical Center
Portland, Oregon, United States
Pathological Complete Response (pCR) Rate (ypT0/Tis ypN0)
Number of patients who showed pCR post surgery. pCR rate (ypT0/Tis ypN0) is defined as the proportion of subjects without residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy per the current AJCC staging criteria assessed by the local pathologist at the time of definitive surgery.
Time frame: Following definitive surgery, approximately 9 months.
Safety and Tolerability Profile as Assessed by CTCAE v5.0
Number of serious adverse events (SAE) reported by patients attributed to study drugs.
Time frame: Cycle 1, Day 1 through safety follow-up visit, approximately 9 months.
Percent Change in Tumor Infiltrating Lymphocytes (TIL) Quantity Changes
Evaluate increase in tumor infiltrating lymphocyte by H\&E (comparing diagnostic biopsy to post-induction biopsy). Tumor infiltrating lymphocytes will be assessed by the San Antonio stromal TIL criteria.
Time frame: Following definitive surgery, approximately 9 months.
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