A Phase 1b Study of Safety and Immune Response to PVX-410 Vaccine Alone and in Combination With Pembrolizumab in HLA-A2+ Patients With Metastatic Triple Negative Breast Cancer (TNBC)
Overview
- Phase
- Phase 1
- Intervention
- Pembrolizumab
- Conditions
- Triple Negative Breast Cancer
- Sponsor
- Massachusetts General Hospital
- Enrollment
- 20
- Locations
- 3
- Primary Endpoint
- Immune Response following treatment with PVX-410 in combination with pembrolizumab
- Status
- Active, not recruiting
- Last Updated
- 7 months ago
Overview
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
Detailed Description
This research study is a Phase Ib clinical trial, which tests the safety of an investigational drug combination and also tries to better understand how the investigational intervention affects the body. "Investigational" means that the FDA (the U.S. Food and Drug Administration) has not approved the combination of PVX-410 and pembrolizumab as a treatment regimen for this specific disease. The FDA has not approved PVX-410 as a treatment for any disease. PVX-410 is a type of vaccine that may help the immune system stimulate immunity against the cancer cells. The FDA has not approved pembrolizumab for this specific disease but it has been approved in the United Sates for other types of cancer. Pembrolizumab is a drug that may treat cancer by working with the immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the immune cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the cells called Programmed Death-1 (PD-1), which then allows these cells and other parts of the immune system to attack tumors. In this research study, the investigators are studying the body's immune response to the PVX-410 study vaccine in combination with pembrolizumab. This study will help researchers understand if the vaccine and pembrolizumab can work together to help the body's immune system recognize and treat triple negative breast cancer. The investigators are also studying the safety of the PVX-410 together with the pembrolizumab
Investigators
Steven J Isakoff, MD, PhD
Principal Investigator
Massachusetts General Hospital
Eligibility Criteria
Inclusion Criteria
- •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.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 (see Appendix section 16.1)
Exclusion Criteria
- •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.
Arms & Interventions
PVX-410
* 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
Intervention: Pembrolizumab
PVX-410
* 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
Intervention: PVX-410
Outcomes
Primary Outcomes
Immune Response following treatment with PVX-410 in combination with pembrolizumab
Time Frame: 3 years
The fold activation of T cells from blood of treated patients at week 10 compared to baseline
Secondary Outcomes
- Late Immune response after treatment with PVX-410 and pembrolizumab(3 years)
- Response rate(3 years)
- Incidence of treatment emergent adverse events (safety and tolerability) of PVX-410 in combination with pembrolizumab(3 years)
- Overall Survival(3 years)
- Progression Free Survival(3 years)