PVX-410 + Durvalumab for Triple Negative Breast Cancer

Recruiting at 4 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Immunosuppressants, PD1/PD-L1 inhibitors

Disqualifiers: Stage IV disease, Autoimmune disease, others

Stay on Your Current Meds You can continue your current medications while participating

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

22 Participants Needed

Trial Summary

What is the purpose of this trial?

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)

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you cannot use immunosuppressive medications within 28 days before starting the trial, except for certain low-dose corticosteroids. It's best to discuss your specific medications with the trial team.

What data supports the effectiveness of the drug Durvalumab for treating triple-negative breast cancer?

Research shows that Durvalumab, when used with chemotherapy, improved overall survival in patients with triple-negative breast cancer, especially in those with certain genetic markers. This suggests it could be a promising option for this type of cancer. ^{1 2 3 4 5}

Is the combination of PVX-410 and Durvalumab safe for humans?

Durvalumab, also known as MEDI4736 or Imfinzi, has been studied in various cancers and generally shows a manageable safety profile. In a study with triple-negative breast cancer patients, some experienced serious side effects like neutropenia (low white blood cell count) and anemia, but no dose-limiting toxicities were observed. Safety data from other studies also suggest it is generally safe, though some patients may experience immune-related side effects. ^{1 4 6 7 8}

How is the drug PVX-410 + Durvalumab different from other treatments for triple-negative breast cancer?

PVX-410 + Durvalumab is unique because it combines a cancer vaccine (PVX-410) with an immune checkpoint inhibitor (Durvalumab), which may enhance the immune system's ability to target and destroy cancer cells. This combination aims to improve treatment outcomes by leveraging the body's immune response, which is different from traditional chemotherapy that directly targets cancer cells. ^{1 2 3 9 10}

Research Team

Steven Isakoff, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

This trial is for women over 18 with Stage II or III Triple Negative Breast Cancer who've finished their planned cancer therapy. They must not have HIV, hepatitis B/C, autoimmune diseases, or certain medical conditions that could affect the study. Participants need to be HLA-A2 positive and willing to use birth control if they can have children.

Inclusion Criteria

Written informed consent and any locally-required authorization obtained from the patient prior to performing any protocol-related procedures, including Screening evaluations.

You do not have HIV, hepatitis B, or hepatitis C.

If not postmenopausal or surgically sterile, study patients must be willing to practice at least one of the specified methods of birth control.

Exclusion Criteria

Participation in another clinical study with an investigational product during the previous 4 weeks.

Pregnant or nursing.

Previous enrollment in the present study.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 6 PVX-410 vaccine injections every 2 weeks and 2 infusions of Durvalumab on the day of the 4th and 6th PVX-410 injection

12 weeks

Follow-up

Participants are monitored for safety and immune response after treatment

4 weeks

Long-term follow-up

Participants are monitored for disease-free survival and adverse events

Up to approximately 5 years

Treatment Details

Interventions

• Durvalumab
• PVX-410 Vaccine

Trial Overview The trial tests a combination of PVX-410 vaccine and Durvalumab (MEDI4736), a PD-L1 inhibitor, as additional treatment after standard care for breast cancer. It aims to assess safety, tolerability, and how well the immune system responds to these treatments in patients.

Participant Groups

Group I: PVX-410 and Durvalumab Experimental Treatment 3 Interventions

Each patient will receive 6 PVX-410 vaccine injections and 2 infusions of Durvalumab. * The injection of PVX-410 will be co-administered with Hiltonol every 2 weeks for 6 injections. * The infusion of Durvalumab will be given on the day of the 4th and 6th PVX-410 injection, for a total of 2 infusions.

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

OncoPep, Inc.

Industry Sponsor

Trials

4

Recruited

120+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Findings from Research

The combination of MEDI0680 and durvalumab was found to be safe and tolerable in patients with advanced clear-cell renal cell carcinoma, but it did not show improved efficacy compared to nivolumab alone, with objective response rates of 16.7% for the combination and 23.8% for nivolumab.

Both treatment groups had a median progression-free survival of 3.6 months, and a notable percentage of patients (23.8% in the combination group) discontinued treatment due to adverse events, highlighting the need for careful monitoring of side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. Voss, MH., Azad, AA., Hansen, AR., et al.[2023]

Durvalumab, a PD-L1 blocking antibody, has shown clinical efficacy and a manageable safety profile in treating advanced non-small-cell lung cancer, especially in patients with ≥25% PD-L1 expression.

The drug is being evaluated in various treatment settings, including as a monotherapy and in combination with other therapies, showing promising results particularly after chemoradiation, although lower response rates were noted in patients with EGFR and ALK mutations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. Mezquita, L., Planchard, D.[2018]

Durvalumab, a PD-L1 inhibitor, has been shown to be safe for patients with various solid tumors, with common side effects including pruritus and fatigue, based on a meta-analysis of 17 studies involving 1,529 patients.

Higher levels of PD-L1 expression in tumors are linked to better treatment responses to durvalumab, indicating that PD-L1 could serve as a useful biomarker for predicting the drug's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. Yang, H., Shen, K., Zhu, C., et al.[2022]

In a Phase I/II trial involving 59 patients with stages I-III triple-negative breast cancer, the combination of durvalumab with chemotherapy resulted in a pathologic complete response (pCR) rate of 44%, indicating its potential efficacy as a neoadjuvant treatment.

The study found that higher levels of stromal tumor-infiltrating lymphocytes (sTILs) were associated with better pCR rates, suggesting that immune response may play a role in treatment effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. Foldi, J., Silber, A., Reisenbichler, E., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Clinical Outcomes and Immune Markers by Race in a Phase I/II Clinical Trial of Durvalumab Concomitant with Neoadjuvant Chemotherapy in Early-Stage TNBC. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

PD-L1 Protein Expression on Both Tumor Cells and Macrophages are Associated with Response to Neoadjuvant Durvalumab with Chemotherapy in Triple-negative Breast Cancer. [2021]

3. England pubmed.ncbi.nlm.nih.gov

A randomised phase II study investigating durvalumab in addition to an anthracycline taxane-based neoadjuvant therapy in early triple-negative breast cancer: clinical results and biomarker analysis of GeparNuevo study. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

A Randomized Phase II Study of MEDI0680 in Combination with Durvalumab versus Nivolumab Monotherapy in Patients with Advanced or Metastatic Clear-cell Renal Cell Carcinoma. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Durvalumab compared to maintenance chemotherapy in metastatic breast cancer: the randomized phase II SAFIR02-BREAST IMMUNO trial. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Durvalumab in non-small-cell lung cancer patients: current developments. [2018]

7. New Zealand pubmed.ncbi.nlm.nih.gov

Safety and efficacy of durvalumab (MEDI4736) in various solid tumors. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Neoadjuvant durvalumab plus weekly nab-paclitaxel and dose-dense doxorubicin/cyclophosphamide in triple-negative breast cancer. [2022]

9. Egypt pubmed.ncbi.nlm.nih.gov

A Meta-Analysis of Efficacy and Safety of PD-1/PD-L1 Inhibitors in Triple-Negative Breast Cancer. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Expression of PD-L1 and BRCA1 in Triple-Negative Breast Cancer Patients and Relationship with Clinicopathological Characteristics. [2023]