Phase 1 Study of Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine and Pepinemab / Trastuzumab in Patients With Metastatic HER2-Positive Breast Cancer

Plain English Summary

Adoptive T Cell Therapy Following HER2-Pulsed Dendritic Cell Vaccine & Pepinemab /Trastuzumab in Patients w/ Metastatic HER2+ Breast Cancer is a Phase 1 clinical trial sponsored by H. Lee Moffitt Cancer Center and Research Institute studying HER2-positive Breast Cancer. This trial tests a new combination therapy including T-cell therapy, a dendritic cell vaccine, and two existing drugs (pepinemab and trastuzumab) for advanced HER2-positive breast cancer. It is for patients with HER2-positive breast cancer that has spread and has not responded well to previous treatments, including trastuzumab and up to 3 chemotherapy regimens. Participation involves receiving the investigational treatments over several weeks, with regular clinic visits for assessments and monitoring. Standard treatment options for this condition may include chemotherapy, hormone therapy, or other targeted therapies, depending on the specific characteristics of the cancer. The trial aims to enroll 28 participants.

Official Summary

The purpose of this study is to test the safety of Adoptive T-Cell therapy following the Dendritic Cell (DC1) study vaccine given in combination with pepinemab added to standard of care therapy, trastuzumab to help people with HER2 positive breast cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with HER2-positive breast cancer that has spread and has progressed on trastuzumab and up to 3 prior chemotherapy regimens. Must have measurable disease and a good performance status (ECOG 0 or 1). Patients with uncontrolled brain metastases, active autoimmune disease, or certain infections are not eligible. Must be able to undergo regular clinic visits and procedures. This trial is studying HER2-positive Breast Cancer, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the highest dose of the T-cell therapy that can be safely given, which is crucial for determining the optimal and safest dose for future patient treatments. The specific primary outcome measures are: Maximum Tolerated Dose (MTD) of expanded CD4 T cells (Up to 6 months). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses a critical need for new treatment options for patients with HER2-positive breast cancer that has become resistant to existing therapies, aiming to improve outcomes where current t This research targets HER2-positive Breast Cancer, where improved treatment options are needed.

Investor Insight

This trial targets a specific subtype of breast cancer with unmet needs, potentially offering a novel immunotherapy approach in a competitive landscape, with early-phase trials indicating a pathway to Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific T-cell therapy, vaccine, and drugs being used, and how they might interact with your current health. Be prepared for regular clinic visits for infusions, blood draws, imaging scans, and physical exams. Understand that this is an early-phase trial, and the long-term effects and full benefits are still being studied. This trial is currently recruiting participants. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: NON_RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 28 participants

Interventions

• BIOLOGICAL: Dendritic Cell (DC1) Vaccine — Participants will receive a DC1 vaccine injection at 1.0-2.0 x 10\^7 cells, either to groin lymph notes or to tumor if accessible once a week for 3 weeks on days 1, 8 and 15. Participants will receive DC1 vaccine boosters every 3 weeks x 3.
• DRUG: Trastuzumab — Participants will receive trastuzumab 8 mg/kg by IV week 1, then 6 mg/kg by IV beginning week 4 and continuing every 3 weeks until disease progression or intolerable toxicity.
• DRUG: Pepinemab — Participants will receive pepinemab 20 mg/kg by IV beginning week 1 and continuing every 3 weeks until disease progression or intolerable toxicity.
• BIOLOGICAL: T-Cell therapy — Participants will receive IL-15 expanded CD4 T cells infusion by IV Day 1 at week 8, 2 weeks from last DC1 vaccine, and IL-7 expanded CD4 T cells infusion IV at week 8 day 8.

Primary Outcomes

• Maximum Tolerated Dose (MTD) of expanded CD4 T cells (Up to 6 months)

Secondary Outcomes

• Overall Response Rate (ORR) (Up to 6 months)
• Clinical Benefit Rate (CBR) of DC1 vaccines and pepinemab/trastuzumab (at 6 months)
• Clinical Benefit Rate (CBR) of expanded CD4 T Cells (at 6 months)
• Progression Free Survival (PFS) (Up to 36 months)

Full Eligibility Criteria

Inclusion Criteria:

* Must have a histologically confirmed HER2 positive breast cancer and must be candidates for trastuzumab therapy as per current standard of care. Note: HER2 positive breast cancer is defined by tumor tissue HER2 overexpression and or tumor HER2 amplification per ASCO/CAP criteria.
* Patients will be eligible regardless of ER/PR status which will be determined per 2020 ASCO/CAP guideline and hormonal therapy will be allowed to continue for patients with ER/PR positive disease.
* Must have evaluable disease, defined as at least one lesion that can be accurately measured ≥ 10 mm by standard imaging techniques that can be include but not limited to CT, PET, PET/CT, MRI. Skeletal disease which is measurable by PET/CT or bone scan will also be allowed.
* Must have had disease progression while on trastuzumab for the treatment of HER2+ MBC and received no more than 3 lines of cytotoxic chemotherapy in the setting of metastatic disease.
* ECOG performance status 0 or 1.
* Must have normal organ and marrow function as defined in protocol within 14 days of registration.
* Left ventricular ejection fraction above institutional lower limit of normal (by echocardiogram or MUGA scan)
* Female patients of childbearing potential must agree to use dual methods of contraception and have a negative serum or urine pregnancy test at screening, and male patients must use an effective barrier method of contraception if sexually active with a female of child-bearing potential. Acceptable methods of contraception are condoms with contraceptive foam, oral, implantable or injectable contraceptives, contraceptive patch, intrauterine device, diaphragm with spermicidal gel, or a sexual partner who is surgically sterilized or post-menopausal. For both male and female patients, effective methods of contraception must be used throughout the study and for 3 months following the last dose. To be considered of not to be of childbearing potential, postmenopausal women must be amenorrheic for at least 12 months naturally (not in the setting of post chemotherapy) or patients must be surgically sterile.
* Must have the ability to understand and the willingness to sign a written informed consent prior to registration on study.
* Must have a life expectancy of at least 12 weeks.

Exclusion Criteria:

* Patients who have had chemotherapy or radiotherapy within 14 days prior to beginning protocol therapy.
* Patients may not be receiving any other investigational agents within 14 days or 5 half-lives (whichever is longer) prior to beginning protocol therapy.
* Patients with uncontrolled brain metastases or leptomeningeal disease
* Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
* Patients with active autoimmune disease or history of autoimmune disease that might recur, which may affect vital organ function or require immune suppressive treatment including chronic prolonged systemic corticosteroids (defined as corticosteroid use of duration one month or greater), should be excluded.
* Female patients who are pregnant or nursing are not eligible.
* Second invasive malignancy requiring active treatment
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS) is not permitted.
* Any known positive test for Hepatitis B or Hepatitis C virus indicating acute or chronic infection is not permitted.
* Patients who have received a live attenuated vaccine ≤30 days of registration are not eligible.
* Patients not able to comply with the treatment schedule and study procedures for any reason are not eligible.
* Patients previously treated with any form of adoptive cell transfer therapy.

Trial Locations

• Moffitt Cancer Center, Tampa, Florida, United States

Frequently Asked Questions

Related Conditions

• Breast Cancer
• HER2-Positive Breast Cancer
• Metastatic Breast Cancer
• Advanced Breast Cancer
• Solid Tumors
• Immunotherapy
• T-Cell Therapy
• Cancer Vaccines
• Targeted Therapy
• Oncology

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