PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ Metastatic Triple Negative Breast Cancer

NCT03362060 | Active Not Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 17-328
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 3

Brief Summary

This research study is studying immunotherapy as a possible treatment for metastatic Triple Negative Breast Cancer (TNBC) in participants who are HLA-A2+. The drugs involved in this study are:

• PVX-410
• Pembrolizumab
• Hiltonol
• Montanide

Conditions

Triple Negative Breast Cancer; Metastatic Breast Cancer

Keywords

Triple Negative Breast Cancer; Vaccine; Immunotherapy; PD-1 Inhibitor; Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Immune Response following treatment with PVX-410 in combination with pembrolizumab

  The fold activation of T cells from blood of treated patients at week 10 compared to baseline

  3 years

Secondary Outcomes (5)

• Late Immune response after treatment with PVX-410 and pembrolizumab

  3 years

• Incidence of treatment emergent adverse events (safety and tolerability) of PVX-410 in combination with pembrolizumab

  3 years

• Progression Free Survival

  3 years

• Overall Survival

  3 years

• Response rate

  3 years

Study Arms (1)

PVX-410

EXPERIMENTAL

* PVX-410 vaccine at W0, 1, 2, 3, 4, and 5 followed by booster PVX-410 vaccine doses at W10 and 28 * Pembrolizumab will be administered every 3 weeks intravenously starting with week 1

Drug: Pembrolizumab; Biological: PVX-410

Interventions

Pembrolizumab DRUG

Pembrolizumab is a monoclonal antibody checkpoint inhibitor that blocks a protein in T-cells cells called PD-1, which then allows these cells and other parts of the immune system to attack tumors

Also known as: Keytruda

PVX-410

PVX-410 BIOLOGICAL

PVX-410 is a type of vaccine composed of 4 9-amino acid peptides that may help the immune system stimulate immunity against cancer cells

PVX-410

Eligibility Criteria

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

You may qualify if:

• Willing and able to provide written informed consent for the study.
• Female aged ≥18 years on the day of signing informed consent.
• HLA A2+ by deoxyribonucleic acid (DNA) sequence analysis (by history with documentation or as part of this study).
• Histopathological diagnosis of metastatic or inoperable locally advanced TNBC that meets the following criteria:
• Triple negative 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 (ASCO)/College of American Pathologists (CAP) guidelines by local testing according to institutional standards.
• For tumors with equivocal interpretation of receptor status (e.g., ER/PR ≥1% "weak" or "faint" staining), the Principal Investigator will have final determination of triple-negative status. For tumors with discrepant receptor results between 2 or more biopsies (including metastatic and/or early stage biopsies), the Principal Investigator will have final determination of triple negative status, but in general the most recent biopsy can be used for eligibility purposes. If receptor testing is not available on a metastatic biopsy, the primary tumor test result is acceptable.
• Metastatic or inoperable locally advanced disease is defined as either: histologically confirmed metastatic breast cancer by biopsy; or locally advanced breast cancer that, in the opinion of the treating physician, is not amenable to curative intent surgical resection; or, radiological or clinical evidence suggestive and supportive of metastatic disease without a documented metastatic biopsy, provided the patient has a prior diagnosis of TNBC that otherwise meets the eligibility criteria.
• Ductal, lobular, mixed, or metaplastic histology.
• Measurable disease, as determined by RECIST 1.1.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix section 16.1)
• At least one line of prior systemic therapy for metastatic or recurrent breast cancer (there is no limit to the number of prior therapies).
• Adequate normal organ and marrow function within 10 days of planned treatment initiation, as defined below:
• Hematologic
• Hemoglobin ≥9.0 g/dL or ≥5.6 mmol/L without transfusion or erythropoietin dependency (within 7 days of assessment)
• Absolute neutrophil count (ANC) ≥1.5x10\^9/L (≥1500 per mm3)

You may not qualify if:

• Currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of study treatment.
• Previous enrollment in the present study.
• Mucinous or tubal histology or other good prognosis histology.
• Known hypersensitivity to any component of PVX-410, Hiltonol®, Montanide, pembrolizumab, or excipients.
• Receipt of the last dose or treatment of anti-cancer chemotherapy, radiotherapy, surgery, endocrine therapy, targeted therapy, biologic therapy, or tumor embolization ≤2 weeks (4 weeks for any monoclonal Antibody (mAb), 6 weeks for nitrosoureas or mitomycin C) prior to first dose of study treatment, or has not recovered (i.e., to ≤Grade 1 or Baseline) from clinically significant Adverse Events (AEs) due to these previously administered agents.
• Patients with ≤Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
• Subjects with other irreversible toxicity (e.g., hearing loss) or reversible toxicity (e.g. 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.
• If patient received major surgery, they must have recovered adequately from the toxicity and/or complications from the intervention prior to starting therapy.
• Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• Received a live vaccine within 30 days of planned start of study therapy.
• Seasonal influenza vaccines for injection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live attenuated vaccines, and are not allowed.
• Ongoing or planned systemic anti-cancer therapy or radiation therapy.
• Pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study, starting with the pre-screening or screening visit through 120 days after the last dose of study treatment.
• Has a known history of active Tuberculosis (Bacillus Tuberculosis).
• History of allogeneic organ transplant.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (3)

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

MeSH Terms

Conditions

Triple Negative Breast Neoplasms; Breast Neoplasms

Interventions

pembrolizumab; PVX-410 vaccine

Condition Hierarchy (Ancestors)

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

Study Officials

• Steven J. 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: Principal Investigator

Study Record Dates

• First Submitted: November 27, 2017
• First Posted: December 5, 2017
• Study Start: December 12, 2017
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)