Personalized Cancer Vaccine (PCV) Strategy in Triple Negative Breast Cancer Patients

Official title

Phase 1 Clinical Trial of a Personalized Cancer Vaccine (PCV) Strategy +/- AB248 (CD8-selective IL-2 Mutein Fusion Protein) in Patients With a New Diagnosis of Triple Negative Breast Cancer Undergoing Neoadjuvant Chemoimmunotherapy

Overview

This is a phase 1 clinical trial to evaluate the safety, feasibility and immunogenicity of a personalized cancer vaccine (PCV) strategy with or without CD8-selective IL-2 mutein fusion protein in patients with triple negative breast cancer undergoing neoadjuvant chemoimmunotherapy.

Interventions

• Drug Paclitaxel
  As part of the KEYNOTE 522 Regimen, given per standard of care.
• Drug Carboplatin
  As part of the KEYNOTE 522 Regimen, given per standard of care.
• Drug Pembrolizumab
  As a part of the KEYNOTE 522 Regimen, given per standard of care. Adjuvant pembrolizumab will be given per standard of care.
• Drug Doxorubicin
  As part of the KEYNOTE 522 Regimen, given per standard of care.
• Drug Cyclophosphamide
  As part of the KEYNOTE 522 Regimen, given per standard of care.
• Biological Personalized cancer vaccine (PCV)
  PCV is given intra-muscular (IM). Each PCV 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.
• Drug AB248
  AB248 is given intravenously (IV) over 30 minutes at the recommended dose.
• Other pVAC tools neoantigen prediction algorithm
  The pVACtools suite of software tools will be used to identify and prioritize cancer neoantigens based on neoantigen identification algorithms.
• Drug poly-ICLC
  Poly-ICLC is mixed with the personalized cancer vaccine (PCV). The PCV is given intramuscularly (IM) at 1mg dose.

Primary outcome measures

• Treatment-emergent adverse events (TEAEs) [Time frame: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)]
• Treatment-related adverse events (TRAEs) [Time frame: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)]
• Serious adverse events (SAEs) [Time frame: Step 1 enrollment to 30 days after completion of PCV treatment (estimated time of 115 days)]
• Feasibility as determined by number of enrolled patients with triple negative breast cancer [Time frame: Completion of enrollment (1 day for patient)]
• Feasibility as determined by time required for PCV design and manufacture [Time frame: Start of Step 0 Enrollment to PCV completion (estimated time of 24 weeks)]
• Feasibility as determined by rate of successful PCV delivery [Time frame: Day 1]

Secondary outcome measures (2)

• Immune response as evaluated by ELISPOT analysis. [Time frame: Step 0 Enrollment to 12 months after PCV completion (estimated time of 18 months and 85 days)]
• Recurrence-free survival (RFS) [Time frame: Step 1 enrollment through completion of follow up (estimated time of 5 years and 85 days)]

Eligibility criteria

Step 0 Inclusion Criteria:

• 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/PCV design or willing to undergo biopsy if adequate tissue is not available.
• 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). Note that patients who are already receiving the KEYNOTE 522 regimen at the time of screening must have adequate archival tissue for nucleic acid isolation/PCV design (biopsy will not be permitted).
• TIL percentage < 10% (performed on SOC biopsy).
• 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.

Step 0 Exclusion Criteria:

• 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.

Step 1 Inclusion Criteria:

• ECOG performance status ≤ 1 within 10 days of initiation of PCV
• Adequate bone marrow and organ function within 28 days of initiation of PCV as defined below:

• Absolute neutrophil count ≥ 1.0 K/cumm
• Platelets ≥ 100 K/cumm
• Hemoglobin ≥ 8.0 g/dL
• Total bilirubin ≤ 1.5 x IULN
• AST(SGOT)/ALT(SGPT) ≤ 3.0 x IULN
• Creatinine clearance > 30 mL/min by Cockcroft-Gault
• The effects of the PCV on the developing human fetus are unknown. For this reason, women of childbearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 6 months after last dose of PCV. Should a woman become pregnant or suspect she is pregnant while participating in this study or should a man suspect he has fathered a child, s/he must inform her treating physician immediately.
• Received at least 4 months of the KEYNOTE 522 regimen.

Step 1 Exclusion Criteria:

• Currently receiving any other investigational agents.
• Pregnant and/or breastfeeding.
• Experiencing ongoing AEs related to the SOC KEYNOTE 522 regimen that have not resolved to < grade 3. Patients may be permitted to enroll with a grade 3 AE with approval of the PI and treating physician.
• QTcF > 470 msec.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Identifiers

NCT: NCT07300475 · 202604114

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗