PVX-410 + Pembrolizumab for Advanced Breast Cancer

Not currently recruiting at 2 trial locations

Age: 18+

Sex: Female

Trial Phase: Phase 1

Sponsor: Massachusetts General Hospital

Must not be taking: Anti-PD-1, Anti-PD-L1

Disqualifiers: Active tuberculosis, CNS metastases, others

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: 6

Duration: 28 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new combination of immunotherapy treatments for advanced Triple Negative Breast Cancer (TNBC), a condition where the cancer doesn't respond to hormonal therapy and has spread beyond the breast. The study uses two drugs, PVX-410 and Pembrolizumab (also known as KEYTRUDA or MK-3475), which aim to boost the body's immune system to fight cancer cells more effectively. Women with metastatic TNBC who are HLA-A2 positive (a specific immune system marker) might be suitable for this study. 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 new combination 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, it mentions that ongoing or planned systemic anti-cancer therapy or radiation therapy is not allowed, and there are specific time frames for stopping certain treatments before starting the trial. It's best to discuss your current medications with the study team to get a clear answer.

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

Research shows that the PVX-410 vaccine is safe and generally well-tolerated. Previous studies found that PVX-410 can trigger an immune response without causing unexpected side effects. Any common issues are manageable and not serious.

Research indicates that pembrolizumab helps improve survival in patients with certain cancers when combined with chemotherapy. It has been tested in many people and is considered safe. Some individuals might experience side effects like tiredness or skin reactions, but these are usually mild.

Both treatments have undergone early studies and are considered safe for further research. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about PVX-410 combined with pembrolizumab for advanced breast cancer because it offers a unique approach to treatment. Unlike traditional therapies such as chemotherapy and hormone therapy, PVX-410 is a vaccine designed to stimulate the immune system to specifically target cancer cells. Meanwhile, pembrolizumab is an immunotherapy that blocks a protein used by cancer cells to evade immune detection, enhancing the body's ability to fight the disease. This combination aims to provide a more targeted and potentially effective treatment by harnessing the body's own immune system against cancer.

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

This trial will evaluate the combination of PVX-410 with pembrolizumab for treating advanced Triple Negative Breast Cancer (TNBC). Research has shown that this combination may be beneficial, as previous studies indicated that 14% of patients experienced their cancer shrinking or stopping growth after 24 weeks. Pembrolizumab, when combined with chemotherapy, has also extended survival in patients with advanced TNBC, with a median survival of 23 months. The PVX-410 vaccine is designed to strengthen the immune system to better attack cancer cells. Together, these treatments aim to enhance the body's natural ability to fight cancer. ^{3 6 7 8 9}

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 metastatic Triple Negative Breast Cancer who are HLA-A2+. They must have had at least one prior systemic therapy, not be pregnant or breastfeeding, agree to use birth control if of childbearing potential, and have no active infections like HIV or hepatitis. Participants should not have received certain vaccines or cancer treatments recently and must be in good health with proper organ function.

Inclusion Criteria

My DNA test shows I am HLA A2 positive.

I am fully active or can carry out light work.

My organs and bone marrow are functioning well.

Exclusion Criteria

I have cancer that has spread to my brain or spinal cord.

I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

I have been treated with drugs targeting PD-1, PD-L1, or PD-L2.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive PVX-410 vaccine at weeks 0, 1, 2, 3, 4, and 5, followed by booster doses at weeks 10 and 28. Pembrolizumab is administered every 3 weeks starting at week 1.

28 weeks

Weekly visits for the first 6 weeks, then at weeks 10 and 28

Follow-up

Participants are monitored for safety and effectiveness after treatment, including immune response and adverse events.

3 years

What Are the Treatments Tested in This Trial?

Interventions

• Pembrolizumab
• PVX-410

Trial Overview The study tests a combination of immunotherapies: PVX-410 vaccine plus Pembrolizumab, along with Hiltonol and Montanide as possible treatments for breast cancer. The goal is to see how well these drugs work together in patients who express the HLA-A2+ molecule.

How Is the Trial Designed?

Group I: PVX-410 Experimental Treatment 2 Interventions

* PVX-410 vaccine at W0, 1, 2, 3, 4, and 5 followed by booster PVX-410 vaccine doses at W10 and 28 * Pembrolizumab will be administered every 3 weeks intravenously starting with week 1

Pembrolizumab is already approved in United States, European Union, United Kingdom for the following indications:

Approved in United States as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in European Union as KEYTRUDA for:

• Head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1
• Melanoma
• Non-small cell lung cancer (NSCLC)
• Urothelial carcinoma
• Colorectal cancer
• Gastric cancer
• Hepatocellular carcinoma
• Renal cell carcinoma
• Cervical cancer
• Endometrial carcinoma

Approved in United Kingdom as KEYTRUDA for:

• Untreated metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) with PD-L1 CPS ≥1

Who Is Running the Clinical Trial?

Massachusetts General Hospital

Lead Sponsor

Trials

3,066

Recruited

13,430,000+

Merck Sharp & Dohme LLC

Industry Sponsor

Trials

4,096

Recruited

5,232,000+

Chirfi Guindo

Merck Sharp & Dohme LLC

Chief Marketing Officer since 2022

Degree in Engineering from Ecole Centrale de Paris, MBA from New York University Stern School of Business

Robert M. Davis

Merck Sharp & Dohme LLC

Chief Executive Officer since 2021

JD from Northwestern University Pritzker School of Law, MBA from Northwestern University Kellogg Graduate School of Management, Bachelor's in Finance from Miami University

Published Research Related to This Trial

Pembrolizumab, a PD-1 inhibitor used in cancer treatment, can lead to rare but serious immune-related adverse events, including type 1 diabetes mellitus, occurring in about 0.2% of cases.

A review of 42 cases revealed that patients may develop diabetic ketoacidosis during treatment, highlighting the need for blood glucose monitoring and awareness of this potential side effect among clinicians.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. Clotman, K., Janssens, K., Specenier, P., et al.[2022]

Pembrolizumab (Keytruda) is approved for treating advanced endometrial carcinoma that is microsatellite instability-high or mismatch repair deficient, specifically for patients whose disease has progressed after previous treatments.

This approval is significant for patients who are not candidates for curative surgery or radiation, providing a new therapeutic option for a challenging stage of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

New Approved Use for Keytruda. Aschenbrenner, DS.[2022]

Pembrolizumab, an immune checkpoint inhibitor, can cause pneumonitis in 1%-5% of patients, and this case report highlights an atypical presentation of this side effect in a patient with metastatic squamous cell carcinoma.

The patient was successfully treated with steroid therapy after ruling out other potential causes, leading to complete resolution of the pneumonitis, emphasizing the importance of recognizing and managing atypical cases of checkpoint inhibitor-pneumonitis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. Jeon, WJ., Nguyen, J., Castillo, DR., et al.[2023]

In the KEYNOTE-010 study involving patients with advanced NSCLC, pembrolizumab significantly improved health-related quality of life (HRQoL) scores compared to docetaxel, indicating better overall patient well-being during treatment.

Patients treated with pembrolizumab experienced less deterioration in symptoms like cough and dyspnea, and showed a significant prolongation in time to deterioration for these symptoms, particularly at the 10 mg/kg dose compared to docetaxel.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced, Programmed Death Ligand 1-Expressing NSCLC. Barlesi, F., Garon, EB., Kim, DW., et al.[2020]

Pembrolizumab, a monoclonal antibody targeting PD-1, showed significant efficacy in treating a 79-year-old patient with advanced squamous cell lung cancer, leading to a complete response after just 3 cycles of treatment.

However, the patient developed acute myelomonocytic leukemia after starting pembrolizumab, highlighting a potential safety concern that warrants further investigation into the drug's effects on blood cell production.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. Kim, HB., Park, SG., Hong, R., et al.[2020]

In a study of 24 patients with advanced non-small cell lung cancer (NSCLC) treated with pembrolizumab, the objective response rate was 45.8%, indicating that nearly half of the patients experienced a reduction in tumor size after treatment.

Pembrolizumab showed promising results even in PD-L1-negative patients, with a major pathological response of 75% and a pathological complete response of 50% in those who underwent surgery, suggesting its potential effectiveness across different patient profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of pembrolizumab for the treatment of advanced non-small cell lung cancer: a retrospective, single-centre, single-arm study. Guo, T., Ding, Y., Chen, L., et al.[2022]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating advanced melanoma, showing an overall response rate of 24% in a trial of 89 patients, with 86% of responses lasting at least 6 months.

While there are potential immune-mediated side effects, the benefits of prolonged tumor response durations were deemed to outweigh these risks, marking an improvement over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. Chuk, MK., Chang, JT., Theoret, MR., et al.[2021]

In a study of 25 patients with advanced ER+/HER2- breast cancer, pembrolizumab showed a modest overall response rate of 12% and a clinical benefit rate of 20%, indicating some effectiveness in this difficult-to-treat population.

The treatment was well tolerated, with 64% of patients experiencing treatment-related adverse events, primarily mild nausea and fatigue, and no treatment-related discontinuations or deaths reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Antitumor Activity of Pembrolizumab in Patients with Estrogen Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer. Rugo, HS., Delord, JP., Im, SA., et al.[2022]

In a phase II trial involving 15 patients with resectable non-small cell lung cancer (NSCLC), neoadjuvant treatment with pembrolizumab showed a major pathologic response in 27% of patients, indicating promising antitumor activity before surgery.

The treatment was found to be feasible and safe, with only 33% of patients experiencing moderate adverse events, and no postoperative mortality, suggesting that pembrolizumab does not compromise surgical outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. Eichhorn, F., Klotz, LV., Kriegsmann, M., et al.[2022]

Pembrolizumab, a PD-1 inhibitor, has demonstrated clinical effectiveness in treating various solid tumors, particularly in patients with PD-L1-positive non-small-cell lung cancer and unresectable/metastatic melanoma.

Early-phase trials and ongoing studies are focused on further confirming the clinical benefits of pembrolizumab in thoracic malignancies, highlighting its potential as a significant treatment option in cancer therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. Karim, S., Leighl, N.[2017]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03362060

PVX-410 Vaccine Plus Pembrolizumab in HLA-A2+ ... This research study is studying immunotherapy as a possible treatment for metastatic Triple Negative Breast Cancer (TNBC) in participants who are HLA-A2+. The ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7650095/

Clinical Data on Immunotherapy in Breast Cancer - PMC At 24 weeks, the researchers observed an overall response rate of 14% (4 patients) and a manageable safety profile [57]. These results seem promising when ...

3. researchgate.net researchgate.net/publication/359118249_Abstract_P2-14-17_A_phase_1b_study_of_PVX-410_vaccine_in_combination_with_pembrolizumab_in_metastatic_triple_negative_breast_cancer_mTNBC

Abstract P2-14-17: A phase 1b study of PVX-410 vaccine in ... Abstract P2-14-17: A phase 1b study of PVX-410 vaccine in combination with pembrolizumab in metastatic triple negative breast cancer (mTNBC).

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04634747?tab=table

Phase 2 Study to Evaluate PVX-410 + Pembrolizumab ... A single-arm, open-label, multi-center phase II study to evaluate the combination of PVX-410 + Pembrolizumab + chemotherapy for frontline therapy of metastatic ...

5. cancer.gov cancer.gov/news-events/cancer-currents-blog/2022/pembrolizumab-triple-negative-breast-cancer-improves-survival

Pembrolizumab for Advanced Triple-Negative Breast Cancer Among patients with this combined positive score, median overall survival was 23.0 months for those who received pembrolizumab and chemotherapy ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2017.35.15_suppl.TPS1126

A phase 1b study of safety and immune response to PVX- ... PVX-410 (PVX) is a novel tetra-peptide vaccine against XBP1 (2 splice variants), CD138 and CS1 that was safe and induced immune responses in a ...

7. aacrjournals.org aacrjournals.org/cancerres/article/82/4_Supplement/P2-14-17/680810/Abstract-P2-14-17-A-phase-1b-study-of-PVX-410

Abstract P2-14-17: A phase 1b study of PVX-410 vaccine in ... Conclusions: PVX plus PEM is safe with manageable toxicity in pts with mTNBC. No new unexpected adverse events were identified. Immune response ...

8. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/30128502/

Assessment of Safety and Immunogenicity of PVX-410 ... Overall, these results suggest that the vaccine is safe and immunogenic in this patient population and support continued study of PVX-410 in SMM.

9. clinicaltrials.gov clinicaltrials.gov/study/NCT02826434

Adjuvant PVX-410 Vaccine and Durvalumab in Stage II/III ... This study will help researchers understand if the vaccine and Durvalumab can work together to help the body's immune system recognize triple negative breast ...