NCT03199040
Terminated
Phase 1
A Randomized Phase 1 Trial of Neoantigen DNA Vaccine Alone vs. Neoantigen DNA Vaccine Plus Durvalumab in Triple Negative Breast Cancer Patients Following Standard of Care Therapy
Washington University School of Medicine1 site in 1 country18 target enrollmentStarted: July 23, 2019Last updated:
ConditionsTriple Negative Breast CancerTriple Negative Breast NeoplasmsTNBC - Triple-Negative Breast CancerTriple-negative Breast Carcinoma
InterventionsDurvalumabNeoantigen DNA vaccineTDS-IM system (Inchor Medical Systems)Peripheral blood draw
DrugsDurvalumab
Overview
- Phase
- Phase 1
- Status
- Terminated
- Enrollment
- 18
- Locations
- 1
- Primary Endpoint
- Safety of Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Number of Adverse Events Experienced by Patient
Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •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 ≥
- •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
Exclusion Criteria
- •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.
Arms & Interventions
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.
Intervention: Durvalumab (Drug)
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.
Intervention: Neoantigen DNA vaccine (Biological)
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.
Intervention: TDS-IM system (Inchor Medical Systems) (Device)
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.
Intervention: Peripheral blood draw (Procedure)
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
Intervention: Neoantigen DNA vaccine (Biological)
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
Intervention: TDS-IM system (Inchor Medical Systems) (Device)
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
Intervention: Peripheral blood draw (Procedure)
Outcomes
Primary Outcomes
Safety of Neoantigen DNA Vaccines Given Alone or in Combination With Durvalumab as Measured by Number of Adverse Events Experienced by Patient
Time Frame: 90 days after completion of treatment (approximately day 259)
* 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
Secondary Outcomes
- 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 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))
- 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))
Investigators
Study Sites (1)
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