HER2 BATs + Pembrolizumab for Breast Cancer

(Breast-47 Trial)

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

33 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, you cannot participate if you are on systemic steroid therapy or any immunosuppressive therapy within 7 days before the trial starts.

What data supports the effectiveness of the treatment HER2 BATs + Pembrolizumab for breast cancer?

Research shows that pembrolizumab, a part of this treatment, has shown clinical benefits in various cancers, including advanced HER2-positive breast cancer when combined with other therapies. Additionally, pembrolizumab has demonstrated activity in different solid tumors, suggesting its potential effectiveness in combination treatments. ^{1 2 3 4 5}

What safety data exists for HER2 BATs and Pembrolizumab in humans?

Pembrolizumab, also known as KEYTRUDA, has been studied in various cancers and is generally considered safe, but it can cause side effects like fatigue, cough, nausea, and immune-related issues such as thyroid problems and lung inflammation. HER2 BATs have been evaluated in combination with pembrolizumab in prostate cancer, but specific safety data for this combination in breast cancer is not detailed in the available research. ^{1 3 4 6 7}

What makes the HER2 BATs + Pembrolizumab treatment unique for breast cancer?

This treatment is unique because it combines HER2 BATs, which are specially armed immune cells targeting HER2 proteins on cancer cells, with pembrolizumab, a drug that helps the immune system attack cancer by blocking a pathway that tumors use to hide from immune cells. This combination aims to enhance the immune response against breast cancer. ^{1 2 3 4 8}

What is the purpose of this trial?

This proposal uses HER2Bi armed activated T-cells (HER2 BATs) to target breast cancer in combination with pembrolizumab (PBZ) in women with metastatic breast cancer (MBC). Phase I will determine a safe dose of the combination of PBZ and HER2 BATs in 3 to 18 patients. In the phase II portion, an additional 12 patients will be treated at the selected dose to further evaluate the safety and preliminary efficacy. Study treatment includes a combination of 8 infusions of BATs using a previously established schedule and one to three infusions of PBZ (200 mg per dose). PBZ will be added to 8 infusions of BATs in 3 schedules: #1) after the 8th BATs infusion; #2) after the 4th and 8th BATs infusions; and then, #3) before the 1st and after the 4th and 8th BATs infusions.

Research Team

Patrick Dillon, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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.

Be willing and able to provide written informed consent for the trial.

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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]

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 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]

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]

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 (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]

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]

References

1. United States 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. [2023]

2. England 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. [2021]

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

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

4. 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]

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

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

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

FDA Approval Summary: Pembrolizumab for the Treatment of Patients with Unresectable or Metastatic Melanoma. [2022]

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

Pembrolizumab Addition Improves Clinical Response in HER2+ Gastric Cancer. [2022]