Neoantigen DNA Vaccine Alone vs. Neoantigen DNA Vaccine Plus Durvalumab in Triple Negative Breast Cancer Patients Following Standard of Care Therapy

NCT03199040 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2017101091R01CA240983-01
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

This is a single institution, open-label randomized phase 1 trial of neoantigen DNA vaccine alone vs. neoantigen DNA vaccine plus durvalumab in triple negative breast cancer (TNBC) patients following standard of care therapy. Patients with newly diagnosed clinical stage II-III TNBC are eligible for enrollment. Patients will receive standard of care therapy including chemotherapy, surgery and radiation therapy as clinically indicated. Following standard of care therapy, patients will be randomized to receive either a neoantigen DNA vaccine alone, or a neoantigen DNA vaccine + durvalumab.

Conditions

Triple Negative Breast Cancer; Triple Negative Breast Neoplasms; TNBC - Triple-Negative Breast Cancer; Triple-negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Safety of Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Number of Adverse Events Experienced by Patient

  * Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events v4.03. * Assessment of the safety of neoantigen DNA vaccines will include both clinical observation and laboratory evaluation. Safety will be closely monitored after injection with eight or more clinical and laboratory assessments in the first 24 weeks of the trial

  90 days after completion of treatment (approximately day 259)

Secondary Outcomes (4)

• Immune Response to Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Luminex Assay

  Up to 1 year after completion of treatment (approximately 1 year and 141 days)

• Number of Participants With an Immune Response to Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Interferon-gamma ELISPOT Assay

  Up to 1 year after completion of treatment (approximately 1 year and 141 days)

• Number of Participants With Immune Response to Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Multiparametric Flow Cytometry - CD4

  Up to 1 year after completion of treatment (approximately 1 year and 141 days)

• Number of Participants With Immune Response to Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Multiparametric Flow Cytometry - CD8

  Up to 1 year after completion of treatment (approximately 1 year and 141 days)

Study Arms (2)

Neoantigen DNA vaccine + Durvalumab

EXPERIMENTAL

* The first neoantigen DNA vaccine injection will take place following the completion of standard of care therapy. The day of the first vaccine injection will be referred to as Day 1 * The schedule of vaccination is Day 1, Day 29 ± 7, Day 57 ± 7, Day 85 ± 7, Day 113 ± 7, and Day 141 ± 7 with at least 21 days between injection days * For patients who are randomized to the neoantigen DNA vaccine plus durvalumab arm, the neoantigen-specific T cell response will be assessed prior to Day 85. If a neoantigen-specific T cell response is present, durvalumab will be started on Day 85, and will be administered Q4W at a dose of 1500 mg over the course of 60 minutes. If a neoantigen-specific T cell response is not present, these patients will be replaced but may continue to receive the neoantigen DNA vaccine on study. They will not be transferred to the vaccine-only arm.

Drug: Durvalumab; Biological: Neoantigen DNA vaccine; Device: TDS-IM system (Inchor Medical Systems); Procedure: Peripheral blood draw

Neoantigen DNA vaccine

EXPERIMENTAL

* The first neoantigen DNA vaccine injection will take place following the completion of standard of care therapy. The day of the first vaccine injection will be referred to as Day 1 * The schedule of vaccination is Day 1, Day 29 ± 7, Day 57 ± 7, Day 85 ± 7, Day 113 ± 7, and Day 141 ± 7 with at least 21 days between injection days

Biological: Neoantigen DNA vaccine; Device: TDS-IM system (Inchor Medical Systems); Procedure: Peripheral blood draw

Interventions

Durvalumab DRUG

-Human monoclonal antibody

Also known as: Imfinzi

Neoantigen DNA vaccine + Durvalumab

Neoantigen DNA vaccine BIOLOGICAL

-The vaccine will be given by the TDS-IM system

Neoantigen DNA vaccine; Neoantigen DNA vaccine + Durvalumab

TDS-IM system (Inchor Medical Systems) DEVICE

-At each vaccination time point, patients will receive two injections at separate sites.

Also known as: Integrated electroporation administration system

Neoantigen DNA vaccine; Neoantigen DNA vaccine + Durvalumab

Peripheral blood draw PROCEDURE

-Baseline, following completion of standard of care therapy, Day 1, Day 57, Day 113, Day 159, and 1 year after initiation of neoantigen DNA vaccine therapy

Neoantigen DNA vaccine; Neoantigen DNA vaccine + Durvalumab

Eligibility Criteria

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

You may qualify if:

• Histologically confirmed diagnosis of invasive breast cancer.
• ER and PR less than Allred score of 3 or less than 1% positive staining cells in the invasive component of the tumor. Patients not meeting this pathology criteria, but have been clinically treated as having TNBC, may be enrolled at treating physician's discretion.
• HER2 negative by FISH or IHC staining 0 or 1+.
• Consented for genome sequencing
• Clinical stage T1c-T4c, any N, M0 primary tumor by AJCC 7th edition clinical staging prior to neoadjuvant chemotherapy, with residual invasive breast cancer after neoadjuvant therapy.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≥1.
• Adequate organ and marrow function no more than 14 days prior to registration as defined below:
• absolute neutrophil count ≥1,500/μL
• platelets ≥100,000/μL
• hemoglobin ≥ 9.0 g/dL
• total bilirubin ≤ 1.5 X institutional upper limit of normal
• AST/ALT ≤2.5 X institutional upper limit of normal
• serum creatinine clearance \>40 mL/min by the Cockcroft-Gault formula or by 24-hour urine collection for determination of creatinine clearance
• Body weight \> 30 kg.

You may not qualify if:

• Received chemotherapy, radiotherapy (to more than 30% of the bone marrow or with a wide field of radiation), or biologic therapy within the last 30 days.
• Concurrent enrollment in another clinical study, unless it is an observational (non-interventional) clinical study or during the follow-up period of an interventional study.
• Receiving any other investigational agent(s) or has received an investigational agent within the last 30 days.
• Receipt of live attenuated vaccination within 6 months prior to study entry or within 30 days of receiving durvalumab.
• Major surgical procedure within 28 days prior to the first dose of durvalumab. Local surgery of isolated lesions for palliative intent is acceptable.
• Current use or prior use of immunosuppressive medication within 28 days before the first dose of durvalumab, with the exceptions of intranasal, inhaled, and intra-articular corticosteroids or systemic corticosteroids at physiological doses which are not to exceed 10 mg/day of prednisone or an equivalent corticosteroid.
• Known metastatic disease.
• Invasive cancer in the contralateral breast.
• Known allergy, or history of serious adverse reaction to vaccines such as anaphylaxis, hives, or respiratory difficulty.
• History of hypersensitivity to durvalumab or any excipient.
• Mean QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms calculated from 3 electrocardiograms (ECGs) (within 15 minutes at 5 minutes apart).
• Uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, evidence of any acute or chronic viral illness or disease, or psychiatric illness/social situation that would limit compliance with study requirements or compromise the ability of the subject to give written informed consent.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., colitis or Crohn's disease\], diverticulitis \[with the exception of diverticulosis\], systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome \[granulomatosis with polyangiitis, Graves' disease, rheumatoid arthritis, hypophysitis, uveitis, etc.\]). The following are exceptions to this criterion:
• Subjects with vitiligo or alopecia
• Subjects with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement

Sponsors & Collaborators

• Washington University School of Medicine: lead
• MedImmune LLC: collaborator
• National Cancer Institute (NCI): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (1)

Washington University School of Medicine

St Louis, Missouri, 63110, United States

Location

Related Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

durvalumab

Condition Hierarchy (Ancestors)

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

Results Point of Contact

• Title: Williams Gillanders, M.D.
• Organization: Washington University School of Medicine

gillandersw@wustl.edu

314-747-0072

Study Officials

• William Gillanders, M.D.

  Washington University School of Medicine

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 22, 2017
• First Posted: June 26, 2017
• Study Start: July 23, 2019
• Primary Completion: November 21, 2022
• Study Completion: May 1, 2023
• Last Updated: May 28, 2024
• Results First Posted: December 14, 2023

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)