PVX-410 + Pembrolizumab for Advanced Breast Cancer

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

20 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug pembrolizumab for advanced breast cancer?

Research shows that pembrolizumab, when used for certain types of advanced breast cancer, was well tolerated and provided a modest but lasting response in some patients. In a study, 12% of patients experienced a partial response, and 20% had a clinical benefit, indicating potential effectiveness in this context. ^{1 2 3 4 5}

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

Pembrolizumab (also known as Keytruda) has been used in various cancer treatments and is generally considered safe, but it can cause side effects. Common side effects include fatigue, nausea, and rash, while more serious immune-related side effects can affect organs like the lungs (pneumonitis) and endocrine organs, sometimes leading to conditions like type 1 diabetes. These side effects are rare but important to consider. ^{1 2 6 7 8}

What makes the drug PVX-410 + Pembrolizumab unique for advanced breast cancer?

This treatment combines PVX-410, a cancer vaccine, with Pembrolizumab, an immune checkpoint inhibitor that helps the immune system attack cancer cells. Pembrolizumab has shown success in treating other cancers by targeting the PD-1 pathway, making this combination a novel approach for advanced breast cancer. ^{1 2 5 9 10}

What is the purpose of this trial?

This research study is studying immunotherapy as a possible treatment for metastatic Triple Negative Breast Cancer (TNBC) in participants who are HLA-A2+. The drugs involved in this study are: * PVX-410 * Pembrolizumab * Hiltonol * Montanide

Research Team

Steven Isakoff, MD, PhD

Principal Investigator

Massachusetts General Hospital

Eligibility Criteria

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.

Currently participating or has participated in a study of an investigational agent within 4 weeks of the first dose of study treatment

Timeline

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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, 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]

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]

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]

References

1. Ireland pubmed.ncbi.nlm.nih.gov

Neoadjuvant anti-programmed death-1 immunotherapy by pembrolizumab in resectable non-small cell lung cancer: First clinical experience. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Pembrolizumab for the treatment of thoracic malignancies: current landscape and future directions. [2017]

3. United States 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. [2020]

4. United States 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. [2022]

5. China 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. [2022]

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

FDA Approval Summary: Accelerated Approval of Pembrolizumab for Second-Line Treatment of Metastatic Melanoma. [2021]

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

Programmed Cell Death-1 Inhibitor-Induced Type 1 Diabetes Mellitus. [2022]

8. England pubmed.ncbi.nlm.nih.gov

Recurrent and atypical immune checkpoint inhibitor-induced pneumonitis. [2023]

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

Acute myelomonocytic leukemia during pembrolizumab treatment for non-small cell lung cancer: A case report. [2020]

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

New Approved Use for Keytruda. [2022]