Clinical Trial 19105

Cancer Type: Breast
Interventions:AMP-514 (Durvalumab); Durvalumab; MEDI4736 (Durvalumab); PVX-410

Study Type: Treatment
Phase of Study: Phase I
Investigators:

  • Hatem Soliman

Overview

Study Title

A Phase 1b Study of Safety and Immune Response to PVX-410 Vaccine Alone and in Combination with an Antibody Targeting the PD-1/PD-L1 Pathway in HLA-A2+ Subjects Who Have Completed Initial Standard Treatment of Stage II or III Triple Negative Breast Cancer (TNBC)

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)

Objective

Primary Objective The primary objective of this study is: - to assess and explore the safety and tolerability of 3 injections of PVX-410 alone followed by 3 doses of PVX-410 in combination with 2 infusions of durvalumab. Secondary Objectives The secondary objectives of this study are: - to perform a pair-wise comparison of the immune response to PVX-410 and PVX-410 plus durvalumab using patients as their own controls. - to assess disease-free survival. - to evaluate correlative immune response indicators. - to compare the safety profile of PVX-410 vaccine regimen alone versus PVX-410 vaccine regimen plus durvalumab.

Inclusion Criteria

  • 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)> Completed all planned therapy for Stage II or III TNBC (American Joint Committee on Cancer, 7th Edition) meeting the following guidelines: a.) 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. b.) All planned radiation therapy surgery for the treatment of the current cancer should be complete (not including plastic or reconstructive surgery). c.) 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.
  • Adequate normal organ and marrow function
  • Negative virology/serology for human immunodeficiency virus (HIV)-1, HIV-2, hepatitis B (surface antigen), and hepatitis C.
  • Must either be of non-reproductive potential or must have a negative serum pregnancy test (β-human chorionic gonadotropin (HCG)) at the Screening visit. If not postmenopausal or surgically sterile, must be willing to practice contraception methods outlined in the study documentation.
  • Willing and able to comply with the protocol for the duration of the study including undergoing treatment and scheduled visits and examinations including follow up.

  • Exclusion Criteria

  • 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 (e.g., hearing loss, peripherally neuropathy) 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.
  • 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 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 (e.g., Crohn's disease, ulcerative colitis).
  • History of primary immunodeficiency.
  • History of allogeneic organ transplant.
  • Uncontrolled intercurrent illness (including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active bleeding diatheses including any patient known to have evidence of acute or chronic hepatitis B, hepatitis C or HIV).
  • Psychiatric illness/social situations that would limit compliance with study requirements or compromise the ability of the patient to give written informed consent.
  • History or clinical evidence of any surgical or medical condition which the Investigator judges as likely to interfere with the results of the study or pose an additional risk in participating.
  • Known history of previous clinical diagnosis of tuberculosis.
  • Receipt of live attenuated vaccination within 30 days prior to study entry or within 30 days of receiving durvalumab.
  • Weight < 30 kg.