PVX-410 + Durvalumab for Triple Negative Breast Cancer

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new approach to treat triple negative breast cancer, a type that doesn't respond to hormonal therapy. It combines a peptide vaccine, PVX-410, with Durvalumab (also known as Imfinzi), which helps the immune system target cancer cells. The goal is to determine if this combination is safe and can enhance the body’s immune response against cancer after primary treatments. This trial may suit individuals who have completed treatment for Stage II or III triple negative breast cancer and show no signs of cancer spreading. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that the PVX-410 vaccine is generally safe and well-tolerated. Previous studies found no unexpected side effects and confirmed that the body recognized and responded to the vaccine as planned.

For durvalumab, studies indicate it is safe for patients with various types of cancer. Reports suggest that while side effects may occur, they are usually not severe and can be managed in a medical setting.

Researchers are carefully studying both treatments to ensure safety for participants. If considering joining a trial, this information suggests that the treatments have been tested and found safe so far. Always consult your doctor to understand what this means for you personally. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Unlike the standard treatments for triple-negative breast cancer, which usually involve chemotherapy, surgery, and radiation, the combination of PVX-410 and Durvalumab offers a novel approach. PVX-410 is a vaccine that trains the immune system to recognize and attack cancer cells, while Durvalumab is an immunotherapy that enhances the immune response by blocking a protein that allows cancer cells to hide from the immune system. Researchers are excited about these treatments because they harness the body's natural defenses to target cancer more precisely, potentially leading to fewer side effects and better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for Triple Negative Breast Cancer?

Research has shown that using PVX-410, a type of vaccine, with Durvalumab, a medicine that aids the immune system, can activate the body's defenses in people with certain cancers. In this trial, participants will receive both PVX-410 and Durvalumab to evaluate their combined effect on triple-negative breast cancer (TNBC). Durvalumab has shown promise in helping patients with TNBC live longer when combined with other treatments. One study found that it helped patients survive longer, even though it only slightly increased the number of cases where the tumor completely disappeared. While specific information about PVX-410 in TNBC is limited, the vaccine is designed to strengthen the immune system to better fight cancer cells. Overall, these treatments are being studied for their potential to help the body combat triple-negative breast cancer more effectively. ^{6 7 8 9 10}

Who Is on the Research Team?

Steven Isakoff, MD, PhD

Principal Investigator

Massachusetts General Hospital

Are You a Good Fit for This Trial?

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.

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

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

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02826434

Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III ... In this research study, the investigators are studying the body's immune response to the PVX-410 study vaccine in combination with Durvalumab.

2. asco.org asco.org/abstracts-presentations/ABSTRACT184859

A phase 1b study of safety and immune response to PVX- ... A phase 1b study of safety and immune response to PVX-410 vaccine alone and in combination with durvalumab (MEDI4736) in HLA-A2+ patients following adjuvant ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35961599/

Neoadjuvant durvalumab improves survival in early triple- ... Conclusions: Durvalumab added to NACT in TNBC significantly improved survival despite a modest pCR increase and no adjuvant component of durvalumab. Additional ...

4. astrazeneca-us.com astrazeneca-us.com/media/press-releases/2023/datopotamab-deruxtecan-plus-imfinzi-durvalumab-demonstrated-robust-and-durable-tumor-responses-in-1st-line-treatment-of-patients-with-metastatic-triple-negative-breast-cancer-in-begonia-phase-ib-ii-trial-10222023.html

Datopotamab deruxtecan plus IMFINZI® (durvalumab) ... AstraZeneca and Daiichi Sankyo's datopotamab deruxtecan plus IMFINZI showed a confirmed objective response rate of 79%.

5. onclive.com onclive.com/view/neoadjuvant-dato-dxd-plus-durvalumab-shows-variable-pcr-rates-in-stage-ii-iii-breast-cancer

Neoadjuvant Dato-DXd Plus Durvalumab Shows Variable ... Datopotamab deruxtecan and durvalumab achieved a 50% pCR rate in high-risk HER2-negative breast cancer, emphasizing the role of RPS in treatment ...

6. ascopubs.org ascopubs.org/doi/abs/10.1200/JCO.2025.43.16_suppl.TPS623

Short-term pre-operative durvalumab (MEDI 4736) in early ... POP-Durva (NCT05215106) is a prospective, single-arm phase II trial evaluating pCR after two doses of durvalumab in Stage I TNBC.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT01693562

NCT01693562 | A Phase 1/2 Study to Evaluate MEDI4736 This is a multicenter, open-label, first-time-in-human study with a standard 3+3 dose-escalation phase in participants with advanced solid tumors.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6038862/

Safety and efficacy of durvalumab (MEDI4736) in various ... Durvalumab is safe in patients with many solid cancers and, in combination with tremelimumab, it has a tolerable safety profile and is associated with improved ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT03356860

Safety and Efficacy of Durvalumab Combined to ... The phase Ib aims to evaluate the safety and tolerability of durvalumab in combination with a dose- dense EC regimen in a neoadjuvant setting for early breast ...

10. dovepress.com dovepress.com/article/download/39200

Safety and efficacy of durvalumab (MEDI4736) in various ... The following data were extracted from eligible articles: 1) the basic characteris- tics of studies, including first author, year of publication, clinical trial ...