HER2 BATs + Pembrolizumab for Breast Cancer

(Breast-47 Trial)

Not currently recruiting at 1 trial location

Overseen By Ashley Donihee

Age: 18+

Sex: Female

Trial Phase: Phase 1 & 2

Sponsor: University of Virginia

Must not be taking: Steroids, Immunosuppressants, Anti-PD-1

Disqualifiers: Immunodeficiency, Active TB, CNS metastases, others

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

Compensation: Varies

Number of Visits: 3

Duration: 7 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a combination of treatments: HER2 BATs (a type of immune cell therapy) and pembrolizumab (an immunotherapy drug), to determine if they can effectively treat metastatic breast cancer together. The goal is to find a safe dose and assess whether this combination can help control the cancer. Women with metastatic breast cancer who have not responded to two or more previous treatments might be suitable candidates for this study. As a Phase 1, Phase 2 trial, this research aims to understand how the treatment works in people and measure its effectiveness in an initial, smaller group.

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 participate if you are on systemic steroid therapy or any immunosuppressive therapy within 7 days before the trial starts.

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

Research has shown that HER2 BATs have been tested in earlier trials, and patients generally handled the treatment well. In one study, about 46.8% of patients who received HER2 BATs had stable disease for at least a month after their last treatment, suggesting that many did not experience severe immediate problems.

Pembrolizumab (PBZ) has been used in various cancer trials. These studies have often found that pembrolizumab, when combined with chemotherapy, can improve survival rates. However, some patients have experienced significant side effects, including immune-related adverse events (irAEs), where the immune system mistakenly attacks healthy cells. This is important to consider when combining it with HER2 BATs.

Overall, both treatments have been studied separately and have shown some level of safety, but they can also cause side effects. Research continues to find the safest way to use them together. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about HER2 BATs combined with Pembrolizumab for breast cancer because of its innovative approach to targeting the disease. Unlike traditional treatments like chemotherapy or hormone therapy, HER2 BATs use bioengineered T cells to directly attack HER2-positive cancer cells, potentially enhancing the immune response against the tumor. Pembrolizumab, an immune checkpoint inhibitor, works by unleashing the body’s immune system to recognize and fight cancer cells more effectively. This combination could offer a more targeted and robust treatment option compared to existing therapies, which may result in improved outcomes for patients with HER2-positive breast cancer.

What evidence suggests that this trial's treatments could be effective for metastatic breast cancer?

Research has shown that HER2 BATs may help treat breast cancer. In one study, 46.8% of patients who received HER2 BATs had stable disease one month after treatment. Additionally, pembrolizumab has helped patients with advanced breast cancer live longer. When combined with chemotherapy, it significantly increased survival compared to chemotherapy alone. This trial will explore different schedules combining HER2 BATs and pembrolizumab to determine if they work better together against metastatic breast cancer. Early results are promising, suggesting they may be more effective when used together. ^{1 2 6 7 8}

Who Is on the Research Team?

Patrick Dillon, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for women over 18 with metastatic breast cancer who have had at least two prior treatments. They must have measurable disease, a life expectancy of more than 3 months, and be able to undergo apheresis. HER2 status can be positive or negative. Participants need functioning major organs and cannot be pregnant or breastfeeding. Exclusions include hypersensitivity to pembrolizumab, certain recent vaccines, active autoimmune diseases requiring treatment in the past two years, other cancers within five years (with some exceptions), and untreated brain metastases.

Inclusion Criteria

My cancer's hormone receptor and HER2 status will be checked.

I have a tumor larger than 10 mm that has not been treated with radiation.

My organ functions are within normal ranges as per recent tests.

Exclusion Criteria

I have stable brain metastases and haven't used steroids for at least 7 days.

Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.

I am currently being treated for an infection.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4-5 weeks

1 visit (in-person)

Treatment

Participants receive 8 infusions of HER2 BATs and 1-3 infusions of Pembrolizumab according to schedule

7 weeks

Multiple visits (in-person) for infusions

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Clinic visits at 2 weeks, 1 month, 3 months, and 6 months after last dose

Long-term follow-up

Participants are monitored for progression-free and overall survival

Every 3 months until death or for 10 years

What Are the Treatments Tested in This Trial?

Interventions

• HER2 BATs
• Pembrolizumab

Trial Overview The study tests HER2Bi armed activated T-cells (HER2 BATs) combined with pembrolizumab on women with metastatic breast cancer. Phase I determines the safe dose for up to 18 patients; phase II treats an additional 12 patients at this dose to assess safety and effectiveness. The treatment involves eight infusions of BATs plus one to three doses of pembrolizumab in different schedules.

How Is the Trial Designed?

Group I: Schedule #3 Experimental Treatment 1 Intervention

At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 3 infusions of pembrolizumab; the first given one week prior to first BATs infusion, the second is given within weeks #3 - 4, and the third at week #7.

Group II: Schedule #2 Experimental Treatment 1 Intervention

At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 2 infusions of Pembrolizumab; the first given within weeks #3 - 4 and the second in week #7.

Group III: Schedule #1 Experimental Treatment 1 Intervention

At approximately 4 weeks following leukapheresis, 8 infusions of HER2 BATs are given twice weekly in weeks #1, #2, #5, and #6 plus 1 infusion of Pembrolizumab in week #7. No interventions within weeks #3 and 4.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

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, 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 patients with hormone receptor-positive metastatic breast cancer, higher levels of specific immune cells (effector memory CD8+ and CD4+ T cells) before treatment were associated with better responses to the combination therapy of palbociclib, pembrolizumab, and letrozole, compared to those receiving only pembrolizumab and letrozole.

The combination therapy also led to significant changes in myeloid cell composition, including increased mature dendritic cells and decreased classical monocytes, which may enhance the immune response against the cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pre-existing effector T-cell levels and augmented myeloid cell composition denote response to CDK4/6 inhibitor palbociclib and pembrolizumab in hormone receptor-positive metastatic breast cancer. Egelston, C., Guo, W., Yost, S., et al.[2021]

In a phase Ib/II trial, the combination of the PD-1 inhibitor pembrolizumab with trastuzumab demonstrated clinical benefits for patients with advanced HER2-positive breast cancer who had become resistant to trastuzumab.

The study identified tumor-infiltrating lymphocyte levels as a potential biomarker, which could help predict how well patients might respond to this combined treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role for Immune Therapy in Advanced Breast Cancer. [2019]

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]

Combining pembrolizumab with trastuzumab and chemotherapy has been shown to reduce tumor size in patients, indicating enhanced efficacy of the treatment.

This combination therapy can also lead to complete responses in some patients, suggesting a potential for significant improvement in cancer treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pembrolizumab Addition Improves Clinical Response in HER2+ Gastric Cancer. [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 phase II study involving 14 patients with metastatic castration-resistant prostate cancer, the combination of HER2 bispecific antibody-armed activated T cells and pembrolizumab showed promising efficacy, with 38.5% of patients achieving 6-month progression-free survival.

The treatment was generally safe, with only mild grade 1-2 infusion reactions reported, indicating that this combination therapy could be a viable option for further research in treating this type of cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 Bispecific Antibody-Armed Activated T Cells in Metastatic Castration-Resistant Prostate Cancer. Vaishampayan, UN., Thakur, A., Chen, W., et al.[2023]

Pembrolizumab (KEYTRUDA) was approved by the FDA for treating unresectable or metastatic melanoma based on two clinical trials involving 1,374 patients, showing significant improvements in overall survival compared to ipilimumab, with hazard ratios indicating a reduced risk of death.

Patients receiving pembrolizumab also experienced significant improvements in progression-free survival, although some immune-mediated adverse reactions like hypothyroidism and pneumonitis were noted, highlighting the importance of monitoring for side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. Barone, A., Hazarika, M., Theoret, MR., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8202097/

Phase II clinical trial using anti-CD3 × anti-HER2 bispecific ... This phase II trial evaluates the efficacy and immune responses of HER2 BATs given to patients with metastatic HER2-estrogen and/or progesterone receptor ...

2. ascopubs.org ascopubs.org/doi/10.1200/JCO.2019.37.15_suppl.1080

Phase II clinical trial using anti-CD3 x anti-HER2 bispecific ... Results: Fifteen of 32 (ORR of 46.8%) who had received any cells had stable disease (SD) at 1 month after the last infusion, and 8 of 15 (25%) ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10093019/

Emerging Targeted Therapies for HER2-Positive Breast Cancer HER2 overexpression is found in approximately 20% of breast cancers and is associated with a poor prognosis and a shorter overall survival.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03272334

Her2-BATS and Pembrolizumab in Metastatic Breast Cancer This proposal uses HER2Bi armed activated T-cells (HER2 BATs) to target breast cancer in combination with pembrolizumab (PBZ) in women with metastatic breast ...

5. biorxiv.org biorxiv.org/content/10.1101/2025.01.04.631323v2.full-text

LAG3+ CD8+ T cell Subset Drives HR+/HER2 This study develops a kinetic-dynamic model of killing of hormone receptor-positive (HR+) breast cancer cells mediated by BATs using single-cell ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04185649

The Efficacy and Safety of BAT8001 Injection for ... The object is to evaluate the safety and efficacy of BAT8001 for the treatment of HER2-positive advanced breast cancer, using lapatinib in combination with ...

7. sciencedirect.com sciencedirect.com/science/article/pii/S0893395222055272

HER2-Low Breast Cancer: Incidence, Clinicopathologic ... Zhang et al reported that 34.5% of HER2-low cases had a high risk of disease recurrence by the MammaPrint assay—28.8% had a luminal B molecular subtype and 4.6% ...

8. aacrjournals.org aacrjournals.org/clincancerres/article/29/1/122/711984/Phase-II-Trial-of-Pembrolizumab-and-Anti-CD3-x

Phase II Trial of Pembrolizumab and Anti-CD3 x Anti-HER2 ... HER2 BATs have been shown to repeatedly kill, proliferate, and release of several cytokines that induce dendritic cells (DC) maturation. The HER2 BATs were ...