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Breast CancerPhase 1NCT02999477

A Study Of Changes In PD-L1 Expression During Preoperative Treatment With Nab-Paclitaxel And Pembrolizumab In Hormone Receptor-Positive Breast Cancer

A Phase 1 study testing Pembrolizumab, Nab-Paclitaxel and Biopsy in people with Breast Cancer, run by Adrienne G. Waks at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for hormone receptor positive breast cancer. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Pembrolizumab, Nab-Paclitaxel and Biopsy
Type of treatment
Surgery or procedure
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteUnited States
Study dates
23 Feb 2017to 8 Jan 2026
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Participants must have histologically or cytologically confirmed invasive breast cancer.
  • Participants must have operable breast cancer, with tumors greater than or equal to 2 cm in size; Participants must not have any evidence of distant metastatic disease. Inflammatory breast cancer is permitted.
  • All confirmed invasive disease must have been tested for ER, PR, and HER2 and participants must have hormone receptor-positive, HER2-negative breast cancer (ER>1% or PR>1%, AND HER2-negative per ASCO CAP guidelines, 2013).
  • Participants with multicentric, multifocal, and/or contralateral cancers are allowed as long as one lesion meets eligibility and no biopsied tumor is HER2+.
  • Prior systemic therapy: No prior chemotherapy, biologic therapy, hormonal therapy or investigational therapy for this operable breast cancer.
  • Prior radiation therapy: No prior radiation to the ipsilateral breast.
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  • The participant is ≥18 years old
  • The participant has an Eastern Cooperative Oncology Group (ECOG) performance status ≤1 (see Appendix A)
  • Participants must have normal organ and marrow function as defined below:
  • Absolute neutrophil count ≥1500/mm3
  • Platelets ≥100,000/mm3
  • Hemoglobin ≥9 g/dL
  • Total Bilirubin ≤1.5 mg/dL (< 2.0 in participants with known Gilbert's syndrome)
  • Serum creatinine ≤1.5 mg/dL OR calculated GFR ≥60mL/min
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 times the upper limit of normal.
  • International normalized ratio (INR) or Prothrombin Time (PT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • Activated Partial Thromboplastin Time (aPTT) <1.5 times the upper limit of normal unless subject is receiving anticoagulant therapy, as long as PT or PTT is within therapeutic range of intended use of anticoagulants.
  • The participant is capable of understanding and complying with the protocol and has signed the informed consent document.
  • The participant must be willing to undergo the three required research biopsies over the course of protocol therapy. Participants who undergo an attempted research biopsy procedure for the purpose of this protocol, and in whom inadequate tissue is obtained, are not required to undergo a repeat biopsy in order to continue on protocol.
  • The effects of pembrolizumab on the developing human fetus are unknown. For this reason, both women and men of child-bearing potential must agree to use adequate contraception (Section 5.5.2) starting with the first dose of study therapy and for the duration of study participation, through 120 days after the last dose of study medication.
  • Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. While on the study, women may not breast-feed. Women of childbearing potential are defined as those who have not been surgically sterilized or have not been free from menses for > 1 year.
  • Female subject of childbearing potential should have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.
  • Participants on bisphosphonates may continue receiving bisphosphonate therapy during study treatment.

Who cannot join

  • The participant has received prior pembrolizumab or any other anti-PD-1, anti-PD-L1, or anti-PD-L2 therapy, or has participated in any prior studies involving pembrolizumab
  • Hypersensitivity to pembrolizumab or any of its excipients.
  • The participant has any history or evidence of active, non-infectious pneumonitis or interstitial lung disease.
  • The participant has an uncontrolled intercurrent illness including, but not limited to, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, congestive heart failure (New York Heart Association Class III or IV; see Appendix B), active ischemic heart disease, myocardial infarction within the previous six months, uncontrolled diabetes mellitus, chronic liver or renal disease, or severe malnutrition.
  • Concurrent use of potent CYP3A4 inhibitors (see Appendix C), such as ketoconazole and erythromycin, should be avoided during the study treatment with nab-paclitaxel.
  • Pregnant women are excluded from this study because pembrolizumab has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with pembrolizumab, breastfeeding should be discontinued if the mother is treated with pembrolizumab.
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  • Active infection requiring intravenous antibiotics at week 1 day 1.
  • Individuals with a history of a second malignancy are ineligible except for the following circumstances. Individuals with a history of other malignancies are eligible if they have been disease-free for at least 5 years and are deemed by the investigator to be at low risk for recurrence of that malignancy. Individuals with the following cancers are eligible if diagnosed and treated within the past 5 years: cervical cancer in situ, and non-melanoma cancer of the skin. Participants with other cancers diagnosed within the past 5 years and felt to be at low risk of recurrence should be discussed with the study sponsor to determine eligibility.
  • The participant has a medical condition that requires chronic systemic steroid therapy or any other form of immunosuppressive medication including disease modifying agents, or has required such therapy in the last 2 years. Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
  • The participant has an active autoimmune disease or a documented history of autoimmune disease or syndrome that requires systemic steroids or immunosuppressive agents.
  • The participant is known to be positive for Hepatitis B surface antigen, or Hepatitis C RNA. Testing for screening is not required.
  • Known HIV-positive participants.HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with pembrolizumab. In addition, these participants are at increased risk of lethal infections with bone marrow suppressive therapy, i.e. nab-paclitaxel. Appropriate studies will be undertaken in participants receiving combination antiretroviral therapy when indicated. Testing for screening is not required.
  • The participant has received a live vaccine within 28 days of planned start of study therapy.
  • Seasonal influenza vaccines for infection are generally inactivated flu vaccines and are allowed; however intranasal influenza vaccines (i.e. Flu-Mist ®) are live attenuated vaccines, and are not allowed.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Pilot Study Of Changes In PD-L1 Expression During Preoperative Treatment With Nab-Paclitaxel And Pembrolizumab In Hormone Receptor-Positive Breast Cancer

This research study is exploring chemotherapy in combination with immunotherapy (a therapy that uses the body's own immune system to control cancer) as a possible treatment for hormone receptor positive breast cancer.

The interventions involved in this study are:

  • Pembrolizumab (MK-3475; Keytruda™)
  • Nab-Paclitaxel (Abraxane
Read the detailed description

This research study is a Pilot Study, which is the first time investigators are examining this study intervention.

In this research study, the investigators are looking at how the participants body and tumor respond to the combination of Nab-paclitaxel and Pembrolizumab. Also, the investigators will be examining the participants tumor tissue to learn more about the disease.

The FDA (the U.S. Food and Drug Administration) has not approved Pembrolizumab for this specific disease; but it has been approved in the United States for the treatment of other diseases.

The FDA has not approved Nab-paclitaxel as a treatment option for this type of breast cancer; but it has been approved in the United States for the treatment of metastatic breast cancer (breast cancer that has spread to other parts of the body).

Pembrolizumab is a medicine that may treat cancer by working with the participant's immune system. The immune system is the body's natural defense against disease. The immune system sends types of cells called "T cells" throughout the body to detect and fight infections and diseases, including cancer. For some types of cancer, the T cells do not work as they should and are prevented from attacking the tumors. Pembrolizumab is thought to work by blocking a protein in the T cells called PD-1 ("programmed death 1"), which then allows these cells and other parts of the immune system to attack tumors.

Nab-paclitaxel (Abraxane) is part of a class of medications called antimicrotubule agents. It works by stopping the growth and spread of cancer cells by blocking the action of proteins called microtubules.

The combination of Pembrolizumab and Nab-paclitaxel is investigational. "Investigational" means that the combination of study drugs is being studied. The study drugs, when given separately, work in different ways to stop the cancer cells from growing and spreading. However, it is not known if giving the two study drugs at the same time will have a better anti-cancer effect than giving each treatment on its own.

Conditions
Breast Cancer
Being tested
Pembrolizumab, Nab-Paclitaxel, Biopsy
Keywords
Breast Cancer
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • PembrolizumabDrug

    Also called Keytruda

    Pembrolizumab will be administered in clinic every three weeks.

  • Nab-PaclitaxelDrug

    Also called Abraxane

    Nab-Paclitaxel will be administered in clinic every week.

  • BiopsyProcedure or surgery

    Biopsies for research purposes will be performed at three separate timepoints during treatment.

Study groups in NCT02999477
Study groupRoleWhat they receive
Nab-PaclitaxelExperimental* 2 weeks Nab-Paclitaxel Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 15 weeks
Receives: Drug: Pembrolizumab; Drug: Nab-Paclitaxel; Procedure: Biopsy
PembrolizumabExperimental* 2 weeks Pembrolizumab Run in * Biopsy will be performed * Post mono therapy Nab-Paclitaxel administered weekly * Post mono therapy Pembrolizumab administered every 3 weeks * Agents administered for a total of 14 weeks
Receives: Drug: Pembrolizumab; Drug: Nab-Paclitaxel; Procedure: Biopsy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in the Biomarker (PD-L1) Expression

    PDL1 H-Score by Immunohistochemistry (≥ 100 versus 0-99) change from baseline biopsy to biopsy after 2-week monotherapy (from C1D1 to C3D1).

    The minimum score is 0 and the higher the score the worse.

    Measured: 2 weeks

Secondary outcomes (4)

  1. Change in Percentage of Stromal Tumor Infiltrating Lymphocytes After Monotherapy Treatment

    stromal tumor infiltrating lymphocytes (sTIL) is measured at C1D1 and C3D1 of the treatment.

    Measured: from C1D1 to C3D1 (2 weeks)

  2. Pathologic Complete Response Rate

    Response is measured by RCB score.RCB 0 (equal to pCR), RCB I(minimal burden), RCB II (moderate burden) and RCB III(extensive burden)

    Measured: 2 years

  3. Overall Response Rate

    Overall response rate, assessed radiographically by both Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) following treatment with combination nab-paclitaxel and pembrolizumab in the neoadjuvant setting. Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable disease (SD), Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the baseline LD. Overall response = CR+PR+SD

    Measured: 2 years

  4. Disease-Free Survival

    Disease-free survival (DFS) will be defined from the time of randomization until the occurrence of the first of the following events:

    • Local/regional recurrence: a recurrent or new invasive ipsilateral breast cancer, invasive breast cancer in the axilla, regional lymph nodes, chest wall, or skin of the ipsilateral breast.
    • Contralateral invasive breast cancer,
    • Distant recurrence: metastatic disease that has either been biopsy confirmed or clinically diagnosed as recurrent invasive breast cancer. A single new lesion on a bone scan without evidence of lytic disease on x-ray and without symptoms does not in and of itself constitute distant recurrence, but multiple new bone lesions, or increased isotope uptake associated with new bone symptoms are more likely due to metastases. Bone metastases must be documented with x-rays and clinical description.
    • Death from any cause

    Measured: 3 years from randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted21 Dec 2016 (estimated)
  2. Study start23 Feb 2017
  3. Primary completion20 Nov 2022
  4. Study completion8 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02999477
Sponsor's protocol ID
16-466
Status last verified
Jan 2026
First submitted
19 Dec 2016
Last updated
29 Jan 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Fu J, Waks AG, Pimenta E, Titchen B, Bi K, Camp S, Pappa T, Keenan T, Shannon E, Vigneau S, Bemus M, Nag A, Thorner AR, Park J, DiLullo M, Wrabel E, Jeselsohn R, Mittendorf EA, Abravanel DL, Tolaney SM, Van Allen EM. Cellular reprogramming during anti-PD-1 and chemotherapy treatment in early-stage primary hormone receptor-positive breast cancer. Nat Commun. 2025 Nov 28;16(1):10704. doi: 10.1038/s41467-025-66659-y.

    PubMed 41315371

  • Waks AG, Fu J, Chu X, Binboga Kurt B, Li T, Kuntz TM, Shen Y, Yang D, Meli K, Reardon B, Park J, Partridge A, Abravanel D, Jeselsohn R, Wrabel E, Alberti J, DiLullo M, Chen S, Mohammed-Abreu A, Sun X, Balko JM, Kleijn M, Audeh W, Morgan XC, Krop IE, Tayob N, Van Allen EM, Mittendorf EA, Tolaney SM. Efficacy, safety, and predictive biomarkers of neoadjuvant nab-paclitaxel and pembrolizumab in hormone receptor-positive breast cancer: A randomized pilot trial. Nat Commun. 2025 Nov 28;16(1):10705. doi: 10.1038/s41467-025-66667-y.

    PubMed 41315271

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Pembrolizumab, Nab-Paclitaxel and Biopsy in people with Breast Cancer, run by Adrienne G. Waks at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 20 Sep 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Biomarker (PD-L1) Expression (time frame: 2 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02999477, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jan 2026.

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Clinical Trial NCT02999477 | AzTrials