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

NCT02999477 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: 16-466
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. The interventions involved in this study are:

• Pembrolizumab (MK-3475; Keytruda™)
• Nab-Paclitaxel (Abraxane

Conditions

Breast Cancer

Keywords

Breast Cancer

Outcome Measures

Primary Outcomes (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.

  2 weeks

Secondary Outcomes (4)

• Change in Percentage of Stromal Tumor Infiltrating Lymphocytes After Monotherapy Treatment

  from C1D1 to C3D1 (2 weeks)

• Pathologic Complete Response Rate

  2 years

• Overall Response Rate

  2 years

• Disease-Free Survival

  3 years from randomization

Study Arms (2)

Nab-Paclitaxel

EXPERIMENTAL

* 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

Drug: Pembrolizumab; Drug: Nab-Paclitaxel; Procedure: Biopsy

Pembrolizumab

EXPERIMENTAL

* 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

Drug: Pembrolizumab; Drug: Nab-Paclitaxel; Procedure: Biopsy

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered in clinic every three weeks.

Also known as: Keytruda

Nab-Paclitaxel; Pembrolizumab

Nab-Paclitaxel DRUG

Nab-Paclitaxel will be administered in clinic every week.

Also known as: Abraxane

Nab-Paclitaxel; Pembrolizumab

Biopsy PROCEDURE

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

Nab-Paclitaxel; Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Adrienne G. Waks: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Publications (2)

• 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.

  PMID: 41315371 RESULT

• 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.

  PMID: 41315271 RESULT

MeSH Terms

Conditions

Breast Neoplasms

Interventions

pembrolizumab; 130-nm albumin-bound paclitaxel; Albumin-Bound Paclitaxel; Biopsy

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Paclitaxel; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Albumins; Proteins; Amino Acids, Peptides, and Proteins; Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Specimen Handling; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques

Results Point of Contact

• Title: Adrienne Waks, MD
• Organization: Dana-Farber Cancer Institute

adrienne_waks@dfci.harvard.edu

617-632-3800

Study Officials

• Adrienne Gropper Waks, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor Investigator

Study Record Dates

• First Submitted: December 19, 2016
• First Posted: December 21, 2016
• Study Start: February 23, 2017
• Primary Completion: November 20, 2022
• Study Completion: January 8, 2026
• Last Updated: January 29, 2026
• Results First Posted: September 20, 2024

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)