This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer immunotherapeutic (PCI) strategy with or without CD8-selective IL-2 mutein fusion protein in patients with triple negative breast cancer undergoing neoadjuvant chemoimmunotherapy.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
30
As part of the KEYNOTE 522 Regimen, paclitaxel is given intravenously (IV) with a dose 80 mg/m2 on Days 1, 8, and 15 of a 21 day cycle after Step 0 enrollment. Paclitaxel will be given a total of 4 cycles (cycles 1-4).
As part of the KEYNOTE 522 Regimen, carboplatin is given intravenously (IV) with a dose of AUC 1.5 on Days 1, 8, and 15 of a 21 day cycle after Step 0 enrollment. Carboplatin will be given a total of 4 cycles (cycles 1-4).
As a part of the KEYNOTE 522 Regimen, pembrolizumab is given intravenously (IV) at a dose of 200 mg on Day 1 of a 21 day cycle after Step 0 enrollment. Pembrolizumab will be given for 8 cycles (cycles 1-8) Pembrolizumab will also be given intravenously (IV) at a dose of 200 mg on days 43, 64, and 85 (same as adjuvant PCI) and then 6 additional doses.
Washington University School of Medicine
St Louis, Missouri, United States
Treatment-emergent adverse events (TEAEs)
Treatment-emergent adverse events (TEAEs) will be assessed via CTCAE v5.
Time frame: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Treatment-related adverse events (TRAEs)
Treatment-related adverse events (TRAEs) will be assessed via CTCAE v5.
Time frame: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Serious adverse events (SAEs)
Serious adverse events (SAEs) will be assessed via CTCAE v5.
Time frame: Step 1 enrollment to 30 days after completion of PCI treatment (estimated time of 115 days)
Feasibility as determined by number of enrolled patients with triple negative breast cancer
Defined as enrolling 24 evaluable patients in 36 months.
Time frame: Completion of enrollment (1 day for patient)
Feasibility as determined by time required for PCI design and manufacture
Defined as completion of design and manufacture within 24 weeks.
Time frame: Start of Step 0 Enrollment to PCI completion (estimated time of 24 weeks)
Feasibility as determined by rate of successful PCI delivery
Defined as at least 70% of patients receiving at least one dose of PCI.
Time frame: Day 1
Immune response as evaluated by ELISPOT analysis.
Samples will be drawn at Step 0 enrollment, day 1, day 15, day 22, day of surgery, day 43, day 64, day 85, and patients randomized to Arm 2 will have an optional draw at Year 1 follow-up.
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As part of the KEYNOTE 522 Regimen, doxorubicin will be given intravenously (IV) at a dose of 60 mg/m2 on Day 1 of a 21 day cycle after Step 0 enrollment. Doxorubicin will be given a total of 4 cycles (cycles 5-8).
As part of the KEYNOTE 522 Regimen, cyclophosphamide is given intravenously (IV) at a dose of 600 mg/m2 dose on Day 1 of a 21 day cycle after Step 0 enrollment. Cyclophosphamide will be given a total of 4 cycles (cycles 5-8).
PCI is given intra-muscular (IM) at 1 mg dose. Each PCI will consists of up to 4 separate injections, with each syringe containing peptides from one of the up to four peptide pools combined with adjuvant poly-ICLC.
AB248 is given intravenously (IV) over 30 minutes at the recommended dose.
The pVACtools suite of software tools will be used to identify and prioritize cancer neoantigens based on neoantigen identification algorithms.
Poly-ICLC is mixed with the personalized cancer immunotherapeutic (PCI). The PCI is given intramuscularly (IM) at 1mg dose.
Time frame: Step 0 Enrollment to 12 months after PCI completion (estimated time of 18 months and 85 days)
Recurrence-free survival (RFS)
Recurrence-free survival is defined as the rate of disease recurrence from Step 1 enrollment until disease recurrence per standard of care assessments or until patient is off study, whichever occurs first.
Time frame: Step 1 enrollment through completion of follow up (estimated time of 5 years and 85 days)