A Randomized, Phase III Trial to Evaluate the Efficacy and Safety of Pembrolizumab (MK-3475) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer With >/= 1 CM Residual Invasive Cancer or Positive Lymph Nodes (ypN1mi, ypN1-3) After Neoadjuvant Chemotherapy

Plain English Summary

Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer is a Phase 3 clinical trial sponsored by National Cancer Institute (NCI) studying Breast Carcinoma In Situ, Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Triple-Negative Breast Carcinoma. This trial tests if pembrolizumab, an immunotherapy drug, can help prevent triple-negative breast cancer from returning after initial treatment. It is for patients who have had triple-negative breast cancer and still have some invasive cancer or positive lymph nodes after chemotherapy and surgery. Participants will receive either pembrolizumab or a placebo (a treatment with no active drug) in addition to standard care. Alternative treatments include standard adjuvant chemotherapy or other targeted therapies depending on the specific cancer characteristics. The trial aims to enroll 1155 participants.

Official Summary

This randomized phase III trial studies how well pembrolizumab works in treating patients with triple-negative breast cancer. Immunotherapy with monoclonal antibodies, such as pembrolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with triple-negative breast cancer that has not spread to distant parts of the body. Must have had chemotherapy before surgery and have at least 1 cm of invasive cancer remaining in the breast or positive lymph nodes after surgery. Patients with HER2-positive breast cancer or those who have received or plan to receive HER2-targeted or hormone therapy are not eligible. Must be able to provide tissue samples for testing and have recovered from side effects of prior chemotherapy, with some exceptions. This trial is studying Breast Carcinoma In Situ, Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Triple-Negative Breast Carcinoma, so participants generally need a confirmed diagnosis.

What They're Measuring

The main goal is to see if pembrolizumab helps patients live longer without their cancer returning or developing a new cancer, which means it aims to improve long-term survival and reduce the risk of The specific primary outcome measures are: Invasive disease-free survival (IDFS) (From date of randomization to date of first invasive recurrence, second invasive primary cancer (breast or not), or death due to any cause, assessed up to 10 years); Severity of fatigue (55 weeks after randomization); Physical function (55 weeks after randomization). 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 3, the final and most rigorous stage before seeking FDA approval. Phase 3 trials involve 300-3,000+ patients across multiple sites and compare the new treatment directly against the current standard of care. These pivotal trials generate the evidence needed for regulatory review. About 58% of Phase 3 drugs receive FDA approval. Successful Phase 3 results typically lead to a New Drug Application submission.

Why This Trial Matters

This trial addresses a critical need for more effective treatments to prevent the recurrence of aggressive triple-negative breast cancer after initial therapy, a common challenge for patients. As a Phase 3 trial, positive results could directly lead to FDA approval, making this treatment available to the broader patient population. This research targets Breast Carcinoma In Situ, Invasive Breast Carcinoma, Stage I Breast Cancer AJCC v7, Stage II Breast Cancer AJCC v6 and v7, Stage III Breast Cancer AJCC v7, Triple-Negative Breast Carcinoma, where improved treatment options are needed.

Investor Insight

This trial investigates a promising immunotherapy for a significant unmet need in breast cancer, potentially expanding the use of pembrolizumab and impacting a substantial market segment if successful Phase 3 trials have approximately a 50-60% chance of gaining FDA approval if they reach this stage. The large enrollment target of 1155 participants suggests significant investment in this program.

Is This Trial Right for Me?

Ask your doctor about the specific criteria for residual disease and lymph node involvement to see if you qualify. Understand that you will be randomly assigned to receive either pembrolizumab or a placebo, and participation involves regular clinic visits for treatment and monitoring. Be prepared for potential side effects of immunotherapy and discuss any concerns about fatigue or physical function with your healthcare team. The trial is being conducted at 20 sites. 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: RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 1,155 participants

Interventions

• PROCEDURE: Biospecimen Collection — Undergo collection of blood samples
• OTHER: Laboratory Biomarker Analysis — Correlative studies
• OTHER: Patient Observation — Undergo standard monitoring
• BIOLOGICAL: Pembrolizumab — Given IV
• OTHER: Quality-of-Life Assessment — Ancillary studies

Primary Outcomes

• Invasive disease-free survival (IDFS) (From date of randomization to date of first invasive recurrence, second invasive primary cancer (breast or not), or death due to any cause, assessed up to 10 years)
• Severity of fatigue (55 weeks after randomization)
• Physical function (55 weeks after randomization)

Secondary Outcomes

• Overall survival (OS) (From date of randomization to date of death due to any cause, assessed up to 10 years)
• Distant recurrence-free survival (DRFS) (From date of randomization to date of invasive distant disease recurrence, second invasive primary cancer (breast or not) or death due to any cause, assessed up to 10 years)
• Incidence of adverse events (Up to 10 years)
• Severity and frequency of treatment-related symptoms (diarrhea, nausea, rash, cough, and shortness of breath, musculoskeletal pain) over time of patients receiving pembrolizumab (Up to 10 years)
• Emotional function and disease-related symptoms in patients receiving pembrolizumab (Up to 10 years)

Full Eligibility Criteria

Inclusion Criteria:

* STEP 1 REGISTRATION
* Patients must have histologically confirmed estrogen receptor (ER)-, progesterone receptor (PR)- and HER2-negative (triple-negative, TNBC) or ER-, PR- weakly positive and/or HER2- equivocal status and must not have received and not be planning to receive adjuvant anti-HER2 or endocrine therapies after completion of neoadjuvant chemotherapy; patients who are HER2-positive by American Society of Clinical Oncology (ASCO) College of American Pathologists (CAP) guidelines are ineligible; HER2-negative and HER2-equivocal cases as per ASCO CAP guidelines that do not receive HER2-targeted therapy are eligible; patients with weakly ER or PR positive disease, defined as ER and/or PR less than or equal to (=\<) 5% by immunohistochemistry, are eligible if the treating physician considers the patient not eligible for adjuvant endocrine therapy; residual disease must be \>= 1 cm in greatest dimension, and/or have positive lymph nodes (ypN1mi, ypN1, ypN2, ypN3) observed on pathologic exam

  * NOTE: If the ER and/or HER2 results are discordant between the initial, pre-chemotherapy, and post-chemotherapy surgical tissue, the receptor status of the residual disease has to be used to determine eligibility. Immunohistochemistry (IHC)-positive isolated tumor cells in the lymph node (N0 \[i+\]) are not considered node-positive and these patients also must have \>= 1 cm residual invasive cancer in the breast to be eligible.
* Patients must not have metastatic disease (i.e., must be clinically M0 or Mx; systemic staging studies with imaging should follow routine practice as per National Comprehensive Cancer Network \[NCCN\] and ASCO guidelines); patients must not have locally recurrent disease
* It is preferred that axillary lymph node sampling is performed after completion of neoadjuvant chemotherapy to allow more accurate assessment of pathologic response; complete axillary lymph node dissection (ALND) after neoadjuvant chemotherapy is recommended in the following situations:

  * Patients had documented pathologic involvement of the axillary nodes (fine needle aspiration \[FNA\] or core biopsy) before neoadjuvant chemotherapy and had sentinel node biopsy after neoadjuvant chemotherapy with positive sentinel node(s)
  * Patient had documented pathologic involvement of the axillary nodes (FNA or core biopsy) before neoadjuvant chemotherapy and had only 1 sentinel lymph node removed after neoadjuvant chemotherapy

    * Except for (i) patients participating in the Alliance A11202 trial) or (ii) if the treating surgeon determines that a complete ALND is not in the best interest of the patient
    * NOTE: Patients who undergo sentinel node biopsy before starting neoadjuvant treatment and do not undergo post neoadjuvant assessment of the axillary nodes or who have negative axillary nodes on post neoadjuvant assessment must have \>= 1 cm residual invasive cancer in the breast after completion of neoadjuvant chemotherapy
* Patients must have a minimum of five, available unstained formalin-fixed paraffin-embedded (FFPE) slides (4-5 micron thickness) from the residual (post-neoadjuvant) invasive tumor in primary site or lymph node; (these will be submitted to a central laboratory to determine PD-L1 expression); the tumor tissue must be adequate for PD-L1 testing, which typically requires a minimum of 100 cancer cells per slide; local PD-L1 results, even if available, will not substitute for central testing

  * NOTE: Initial order for specimen kits should be placed at least two weeks prior to registering the first patient at each site
* Patients must be offered the opportunity to participate in specimen banking
* The BAHO substudy was permanently closed to accrual on June 23, 2020, and willingness of English-speaking patients to participate in the BAHO substudy is no longer applicable
* Patients must have had neoadjuvant chemotherapy followed by surgery; the choice of neoadjuvant chemotherapy is determined by the treating physician; we recommend following the National Comprehensive Cancer Network (NCCN) treatment guidelines for TNBC; patients who cannot complete all planned treatment cycles for any reason are considered high risk and therefore are eligible for the study if they have residual disease; patients must have resolution of adverse event(s) of the most recent prior chemotherapy to grade 1 or less, except alopecia and =\< grade 2 neuropathy which are allowed
* Patients may receive post-operative (adjuvant) chemotherapy for up to 24 weeks of duration (e.g. 8 cycles of capecitabine as in the Capecitabine for Residual Cancer as Adjuvant Therapy (CREATE-X) trial; the 24-week duration does not include treatment delays) after completion of surgery at the discretion of the treating physician; co-enrollment to EA1131 is allowed, provided that patients complete or discontinue adjuvant chemotherapy prior to step 1 registration; at the time of step 1 registration, patients must have resolution o

Trial Locations

• University of Alabama at Birmingham Cancer Center, Birmingham, Alabama, United States
• Southern Cancer Center PC-Daphne, Daphne, Alabama, United States
• Southern Cancer Center PC-Mobile, Mobile, Alabama, United States
• Southern Cancer Center PC-Providence, Mobile, Alabama, United States
• Southern Cancer Center PC-Springhill, Mobile, Alabama, United States
• University of South Alabama Mitchell Cancer Institute, Mobile, Alabama, United States
• Alaska Oncology and Hematology LLC, Anchorage, Alaska, United States
• Anchorage Oncology Centre, Anchorage, Alaska, United States
• Katmai Oncology Group, Anchorage, Alaska, United States
• Providence Alaska Medical Center, Anchorage, Alaska, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Breast Cancer
• Triple-Negative Breast Cancer
• Invasive Breast Carcinoma
• Estrogen Receptor Negative Breast Cancer
• Progesterone Receptor Negative Breast Cancer
• HER2 Negative Breast Cancer
• Stage I Breast Cancer
• Stage II Breast Cancer
• Stage III Breast Cancer
• Metastatic Breast Cancer (ineligible, but related)

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