Cancer Immunotherapeutic (PCI) Strategy in Triple Negative Breast Cancer Patients

NCT07300475 | Not Yet Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 25-x465
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Triple Negative Breast Cancer

Keywords

Personalized medicine; IL-2; Cancer neoantigen; Personalized cancer immunotherapeutic; Personalized cancer vaccine

Outcome Measures

Primary Outcomes (6)

• Treatment-emergent adverse events (TEAEs)

  Treatment-emergent adverse events (TEAEs) will be assessed via CTCAE v5.

  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.

  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.

  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.

  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.

  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.

  Day 1

Secondary Outcomes (2)

• Immune response as evaluated by ELISPOT analysis.

  Step 0 Enrollment to 12 months after PCI completion (estimated time of 18 months and 85 days)

• Recurrence-free survival (RFS)

  Step 1 enrollment through completion of follow up (estimated time of 5 years and 85 days)

Study Arms (2)

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab

EXPERIMENTAL

Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen for eight 21-day cycles. Patients will take a 2-week drug holiday from the end of SOC neoadjuvant chemoimmunotherapy to the start of personalized cancer immunotherapeutic (PCI). Patients will receive 5 doses of the PCI + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCI + poly-ICLC. Patients will receive 9 doses of SOC adjuvant pembrolizumab on a 21-day cycle. The PCI + poly-ICLC will be given on Days 43, 64, and 85.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Biological: Personalized cancer immunotherapeutic (PCI); Other: pVAC tools neoantigen prediction algorithm; Drug: poly-ICLC

Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

EXPERIMENTAL

Patients will be treated with standard of care (SOC) neoadjuvant chemoimmunotherapy according to the KEYNOTE 522 regimen for eight 21-day cycles. Patients will take a 2-week drug holiday from the end of SOC neoadjuvant chemoimmunotherapy to the start of personalized cancer immunotherapeutic (PCI). Patients will receive 5 doses of the PCI + poly-ICLC on Days 1, 4, 8, 15, and 22. Patients will also receive 2 doses of AB248. Patients will undergo the SOC surgery on Day 29 +/- 5 days. Following surgery, patients will receive 3 additional doses of the PCI + poly-ICLC. Patients will receive 9 doses of SOC adjuvant pembrolizumab on a 21-day cycle. The PCI + poly-ICLC will be given on Days 43, 64, and 85.

Drug: Paclitaxel; Drug: Carboplatin; Drug: Pembrolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Biological: Personalized cancer immunotherapeutic (PCI); Drug: AB248 (CD8-selective IL-2 mutein fusion protein); Other: pVAC tools neoantigen prediction algorithm; Drug: poly-ICLC

Interventions

Paclitaxel DRUG

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).

Also known as: Onxol, Taxol

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Carboplatin DRUG

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).

Also known as: KYXATA, Paraplatin

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Pembrolizumab DRUG

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.

Also known as: Keytruda

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Doxorubicin DRUG

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).

Also known as: Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Cyclophosphamide DRUG

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).

Also known as: Cytoxan, Neosar, Frindovyx

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

poly-ICLC DRUG

Poly-ICLC is mixed with the personalized cancer immunotherapeutic (PCI). The PCI is given intramuscularly (IM) at 1mg dose.

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Personalized cancer immunotherapeutic (PCI) BIOLOGICAL

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.

Also known as: CD8-selective IL-2 mutein fusion protein

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

AB248 (CD8-selective IL-2 mutein fusion protein) DRUG

AB248 is given intravenously (IV) over 30 minutes at the recommended dose.

Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

pVAC tools neoantigen prediction algorithm OTHER

The pVACtools suite of software tools will be used to identify and prioritize cancer neoantigens based on neoantigen identification algorithms.

Arm 1: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab; Arm 2: Neoadjuvant SOC KEYNOTE 522 + Adjuvant PCI + Pembrolizumab+AB248

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Newly diagnosed, previously untreated, locally advanced non-metastatic triple negative breast cancer (as defined by the most recent ASCO/CAP guidelines). Permissible staging per AJCC is as follows:
• T1c, N1-N2
• T2, N0-N2
• T3, N0-N2
• At least 18 years of age.
• Adequate tissue available for nucleic acid isolation/PCI design.
• Adequate cardiac function per treating physician and a candidate for the KEYNOTE 522 regimen (or receiving the KEYNOTE 522 regimen for no more than one month).
• Ability to understand and willingness to sign an IRB approved written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants.

You may not qualify if:

• Prior or concurrent malignancy whose natural history has the potential to interfere with the safety or efficacy assessment of the investigational regimen. Patients with prior or concurrent malignancy that does NOT meet that definition are eligible for this trial.
• Received prior chemotherapy, targeted therapy, or radiation therapy within the past 12 months.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another co-inhibitory T-cell receptor.
• Currently receiving any other investigational agents.
• A history of allergic reactions attributed to compounds of similar chemical or biologic composition to any agents used in the study.
• Received a live vaccine within 30 days of the first dose of pembrolizumab.
• Active autoimmune disease that has required systemic treatment in the past 2 years.
• Diagnosis of immunodeficiency or receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of pembrolizumab.
• History of (non-infectious) pneumonitis that required steroids, or current pneumonitis.
• Uncontrolled intercurrent illness including, but not limited to: ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Patients with a known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the New York Heart Association Function Classification; to be eligible for this trial, patients should be a class 2B or better.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negative pregnancy test within 7 days of study entry.
• Known history of active TB (bacillus tuberculosis).
• Known history of HIV.
• Evidence of chronic hepatitis B virus (HBV) that is detectable on suppressive therapy. Patients with evidence of chronic HBV infection with undetectable HBV viral load on suppressive therapy are eligible. HBV testing not required in the absence of known history of infection.
• History of hepatitis C virus (HCV) infection that has not been cured or that has a detectable viral load. Patients with a history of HCV that has been treated and cured are eligible. Patients with HCV infection who are currently on treatment and have an undetectable HCV viral load are eligible. HCV testing not required in the absence of known history of infection.

Sponsors & Collaborators

• Washington University School of Medicine: lead

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Paclitaxel; Carboplatin; pembrolizumab; Doxorubicin; Cyclophosphamide; poly ICLC

Condition Hierarchy (Ancestors)

Breast Neoplasms; Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds

Study Officials

• William Gillanders, MD

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

William Gillanders, MD

CONTACT

314-747-0072; gillandersw@wustl.edu

Katherine Clifton, M.D.

CONTACT

314-273-3712; k.clifton@wustl.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 9, 2025
• First Posted: December 23, 2025
• Study Start: March 31, 2026
• Primary Completion (Estimated): January 8, 2030
• Study Completion (Estimated): December 9, 2034
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)