Testing MK-3475 (Pembrolizumab) as Adjuvant Therapy for Triple Receptor-Negative Breast Cancer

Running, not enrolling · Phase 3

Conditions studied: 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

In brief

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.

Key facts

Study ID

NCT02954874

Run by

National Cancer Institute (NCI)

People needed

1155

Starts

2017-01-18

Expected to finish

2026-08-31

Last updated by the study team

2026-07-31

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 of adverse event(s) of the most recent prior chemotherapy to =< grade 1, except alopecia and =< grade 2 neuropathy which are allowed; patients that have received adjuvant chemotherapy (including via co-enrollment to EA1131) must be registered to step 1 within 35 days after final dose of adjuvant chemotherapy
• Patients must have completed their final breast surgery (rendering them free from disease) with clear resection margins for invasive cancer and DCIS within the following timelines:
• 90 days prior to step 1 screening registration for patients not receiving post-operative (adjuvant) chemotherapy OR
• 270 days prior to step 1 screening registration for patients who have received post-operative (adjuvant) chemotherapy Positive margins are allowed only if the surgical team of the patient deems further resection impossible
• Patients for whom radiation therapy (RT) to the affected breast or chest wall and regional nodal areas is clinically indicated as per NCCN treatment guidelines, should receive routine RT after randomization when possible, and receive MK-3475 (pembrolizumab) concurrent with RT, if randomized to the experimental arm; however, routine RT administered, or initiated, prior to registration is also allowed; MK-3475 (pembrolizumab) may be added to ongoing radiation, or started after its completion, if randomized to the experimental arm, provided there are no > grade 1 radiation-related skin toxicities and provided that no radiosensitizing chemotherapy is being administered; co-enrollment in the Alliance A221505 (NCT03414970) and A011202 (NCT01901094) trials or in the NSABP-B51 (NCT01872975) trial is allowed, but patients must not be planning to receive radiation therapy given on these trials concurrently with MK-3475 (pembrolizumab) treatment on S1418/BR006; whether or not patient will receive RT and the extent of intended RT must be specified at time of registration; NOTE: Patients who receive post-operative chemotherapy may receive radiation therapy before or after the chemotherapy; a short course of reduced dose chemotherapy or other agents concomitant with radiation for radiation sensitization is not considered to be adjuvant chemotherapy
• Patients must not have had prior immunotherapy with anti-PD-L1, anti-PD-1, anti-CTLA4 or similar drugs; patients must not be planning to receive any of the prohibited therapies during the screening or treatment phases of the study
• Patients must not be planning to receive concomitantly other biologic therapy, hormonal therapy, other chemotherapy, surgery or other anti-cancer therapy except radiation therapy while receiving treatment on this protocol; however, patients receiving extended adjuvant endocrine therapy for an earlier ER positive breast cancer treated with curative intent and without recurrence for at least 5 years may continue with their endocrine therapy; elective surgery or surgery that is not related to cancer therapy is allowed, at the discretion of the treating investigator
• Patients must be >= 18 years of age
• Patients must have Zubrod performance status =< 2
• Patients must not have a history of (non-infectious) pneumonitis that required steroids or evidence of active pneumonitis within 2 years prior to registration
• Patients must not have active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids or immunosuppressive drugs); replacement therapy (e.g., thyroxine for pre-existing hypothyroidism, insulin for type I diabetes mellitus, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment

Where it is running

• 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
• Fairbanks Memorial Hospital — Fairbanks, Alaska, United States
• Banner MD Anderson Cancer Center — Gilbert, Arizona, United States
• CTCA at Western Regional Medical Center — Goodyear, Arizona, United States
• Banner University Medical Center - Tucson — Tucson, Arizona, United States
• University of Arizona Cancer Center-North Campus — Tucson, Arizona, United States
• NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro — Jonesboro, Arkansas, United States
• University of Arkansas for Medical Sciences — Little Rock, Arkansas, United States
• Highlands Oncology Group - Rogers — Rogers, Arkansas, United States
• Kaiser Permanente-Anaheim — Anaheim, California, United States
• Kaiser Permanente-Deer Valley Medical Center — Antioch, California, United States
• PCR Oncology — Arroyo Grande, California, United States
• Sutter Auburn Faith Hospital — Auburn, California, United States
• AIS Cancer Center at San Joaquin Community Hospital — Bakersfield, California, United States
• Kaiser Permanente-Baldwin Park — Baldwin Park, California, United States
• Kaiser Permanente-Bellflower — Bellflower, California, United States
• University of Alabama at Birmingham Cancer Center — Birmingham, Alabama, United States

Full record on ClinicalTrials.gov

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