Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III Triple Negative Breast Cancer

NCT02826434 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 16-132
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this research study is to evaluate Immunotherapy with a peptide vaccine and Programmed Death Ligand 1 (PD-L1) inhibitor as a possible adjuvant treatment for Stage II or III Triple Negative Breast Cancer. This research study is studying the safety, tolerability, and immune response of these treatments. The names of the study interventions involved in this study are:

• PVX-410 Vaccine
• Durvalumab (MEDI4736)

Conditions

Breast Cancer

Keywords

Breast Cancer; vaccine; immunotherapy; PD-L1 Inhibitor; triple negative breast cancer

Outcome Measures

Primary Outcomes (1)

• Dose Limiting Toxicity Rate of PVX-410 in Combination With Durvalumab

  To assess the safety of the vaccine and PDL1 inhibitor.

  4 Weeks

Secondary Outcomes (3)

• Immune Response Rate of cluster designation 8 (CD8)+ Cytotoxic T Lymphocytes (CTLs) to Vaccine-Specific Peptides

  14 weeks from first dose

• Disease-Free Survival

  Up to approximately 5 years

• Adverse events according to Common Toxicology Criteria for Adverse Events (CTCAE 4.0) will be assessed for the PVX-410 vaccine regimen alone versus PVX-410 vaccine regimen plus durvalumab

  From the start of treatment until 30 days after the end of treatment, up to approximately 14 weeks

Study Arms (1)

PVX-410 and Durvalumab

EXPERIMENTAL

Each patient will receive 6 PVX-410 vaccine injections and 2 infusions of Durvalumab. * The injection of PVX-410 will be co-administered with Hiltonol every 2 weeks for 6 injections. * The infusion of Durvalumab will be given on the day of the 4th and 6th PVX-410 injection, for a total of 2 infusions.

Biological: PVX-410; Biological: Durvalumab; Drug: Hiltonol

Interventions

PVX-410 BIOLOGICAL

This is a Vaccine that will be injected intramuscularly as a mixture with an adjuvant.

PVX-410 and Durvalumab

Durvalumab BIOLOGICAL

This is an intravenous infusion of a monoclonal antibody.

Also known as: MEDI4736

PVX-410 and Durvalumab

Hiltonol DRUG

This is an intramuscular injection of an adjuvant to enhance the immune response to vaccine.

Also known as: poly-ICLC

PVX-410 and Durvalumab

Eligibility Criteria

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

You may qualify if:

• Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including Screening evaluations.
• Females, ≥18 years at time of study entry.
• HLA-A2 positive by deoxyribonucleic acid (DNA) sequence analysis (by history or as part of this study).
• Histopathological diagnosis of triple negative breast cancer(TNBC) (ductal, lobular, mixed or metaplastic), defined as estrogen receptor (ER)\<1%, progesterone receptor (PR)\<1%, and Human Epidermal growth factor Receptor 2 (HER2) negative according to American Society of Clinical Oncology/College of American Pathologists guidelines by local testing according to institutional standards. For tumors with equivocal interpretation of receptor status (e.g. "weak" or "faint" staining, the Principal Investigator will have final determination of triple negative status.
• Completed all planned therapy for Stage II or III TNBC (American Joint Committee on Cancer, 7th Edition) meeting the following guidelines:
• received neoadjuvant chemotherapy with residual invasive disease at surgery and/or completed adjuvant chemotherapy with or without radiation. (The patient may have had adjuvant and/or neoadjuvant chemotherapy for their disease). Adjuvant/neoadjuvant chemotherapy regimens must include at least 4 cycles of a standard chemotherapy regimen, and generally this should include one of the generally accepted standard regimens (including but not limited to: Adriamycin/Cytoxan-Taxol, Taxotere/Cytoxan, Adriamycin/Cytoxan, or Cytoxan/Methotrexate/Fluorouracil). For patients who received their standard chemotherapy as part of a clinical trial, the regimen should include at least 4 cycles of therapy.
• All planned radiation therapy surgery for the treatment of the current cancer should be complete (not including plastic or reconstructive surgery).
• Patients with local-regional recurrence without evidence of distant metastases (no definite stage IV disease) who are treated with curative intent may be eligible following completion of all surgery and/or chemotherapy and/or radiotherapy. Such patients must have no evidence of residual disease by standard clinical and radiological examination (per Investigator discretion) following completion of curative intent treatment.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix B).
• Adequate normal organ and marrow function as defined below:
• Hemoglobin ≥9.0 g/dL.
• absolute neutrophil count (ANC) ≥1.5 109/L (≥1500 per mm3).
• Platelet count ≥100 109/L (\>100,000 per mm3).
• Serum bilirubin ≤1.5 institutional upper limit of normal (ULN). This will not apply to patients with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology).
• aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ≤2.5 ULN.

You may not qualify if:

• Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• Previous enrollment in the present study.
• Receipt of the last dose or treatment of anti-cancer therapy for the current cancer (chemotherapy, radiotherapy, surgery, immunotherapy, endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal antibodies, other investigational agent) ≤4 weeks (6 weeks for nitrosoureas or mitomycin C) or \>6 months prior to first dose of study drug.
• Any unresolved clinically significant treatment related toxicity of ≥Grade 1 intensity, as assessed using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), from previous anti-cancer therapy. Patients with irreversible toxicity (eg, hearing loss, peripherally neuropathy) or reversible toxicity (eg, alopecia) that is not reasonably expected to be exacerbated by the investigational product and is not expected to interfere with study participation may be included.
• Participation in another clinical study with an investigational product during the previous 4 weeks.
• Any previous treatment with a programmed cell death protein 1 (PD1) or PD-L1 inhibitor, including durvalumab.
• Stage IV disease, confirmed by biopsy or unequivocal radiographic evidence (note: staging scans are not required, but should be performed at treating physician discretion in accordance with standard guidelines).
• Mucinous or tubal histology or other good prognosis histology.
• Ongoing or planned systemic anti-cancer therapy or radiation therapy.
• Pregnant or nursing.
• Known hypersensitivity to any component of the investigational product (PVX-410, durvalumab, or any excipient).
• Mean QT interval corrected for heart rate (QTc) ≥470 ms calculated from 3 electrocardiograms (ECGs) using Frediricia's Correction.
• Active or prior documented active autoimmune disease that has required systemic treatment. Note: Patients with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within the past 2 years) are not excluded.
• Current or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal and inhaled corticosteroids or systemic (oral or iv) corticosteroids at physiological doses, which are not to exceed 10 mg/day of prednisone, or an equivalent corticosteroid.
• Active or prior documented inflammatory bowel disease (eg, Crohn's disease, ulcerative colitis).

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• OncoPep, Inc.: collaborator
• AstraZeneca: collaborator

Study Sites (5)

Lee Moffitt Cancer Center and Research Institute

Tampa, Florida, 33607, United States

Location

Massachusetts general Hospital

Boston, Massachusetts, 02114, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02115, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

New York University School of Medicine

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

PVX-410 vaccine; durvalumab; poly ICLC

Condition Hierarchy (Ancestors)

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

Study Officials

• Steven Isakoff, MD, PhD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Steven Isakoff MD PhD

Study Record Dates

• First Submitted: July 5, 2016
• First Posted: July 11, 2016
• Study Start: August 18, 2016
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): September 1, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)