Breast Cancer Study of Preoperative Pembrolizumab + Radiation

NCT03366844 | Active Not Recruiting Phase 1 Results DMC FDA Drug

• 1 other identifier: IIT2017-07-HO-PembroRT
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being done to assess the feasibility of pembrolizumab (study drug) combined with standard radiation to the tumor (tumor boost) before patients undergo standard treatment that can consist of one or more of the following: breast-conserving surgery, radiation to the entire breast/chest wall after surgery, and chemotherapy. Study participants will receive two doses of the study drug intravenously (through the vein) before their planned breast surgery or chemotherapy. The study drug will be administered three weeks apart. At the time of the second dose, radiation to the tumor in the affected breast will be given. This type of radiation treatment is called a "tumor boost", which is a standard part of radiation therapy for breast cancer that may occur either before or after planned breast-conserving surgery. Patients will receive breast surgery or begin chemotherapy approximately six weeks after your first dose of the study drug.

Conditions

Breast Cancer

Keywords

invasive adenocarcinoma of the breast; ER-positive and HER2-negative breast cancer; Triple negative breast cancer (TNBC); immunotherapy; checkpoint inhibitor; HR-positive

Outcome Measures

Primary Outcomes (2)

• Number of Patients Who do Not Necessitate a Delay in Standard of Care Treatment After Receiving the Investigational Combination of Preoperative Pembrolizumab and Radiation

  Feasibility of preoperative radiation and Pembrolizumab in newly diagnosed, non-metastatic patients with triple negative breast cancer.

  8 weeks after trial initiation

• Changes in Tumor Infiltrating Lymphocyte Score (TILs)

  An increase in the tumor-infiltrating lymphocyte score (TILs) as measured by Salgado criteria. An increase in TILs is an indicator of immune system engagement (range is 0-100 in percent), therefore increase indicates better outcome. A lead in with pembrolizumab alone followed by the combination of pembrolizumab with RT will allow for serial assessment of TILs. This will establish the contribution of RT to the immune response generated by pembrolizumab. The working group's consensus for Salgado criteria is that TILs may provide more biological relevant information when scored as a continuous variable. The percentage of stromal TILs is a semi quantitative parameter for this assessment (0%-100%). No formal recommendation for a clinically relevant TIL threshold(s) can be given at this stage. The consensus was that a valid methodology is currently more important than issues of thresholds for clinical use, which will be determined once a solid methodology is in place.

  8 weeks after trial initiation

Secondary Outcomes (4)

• Pembrolizumab-related Adverse Events

  15 weeks after trial initiation

• Immune-related Adverse Events

  Assessed up to one year post-treatment

• Invasive Disease-free Survival After Preoperative Radiation and Pembrolizumab

  From treatment start date until date of documented recurrence or death from breast cancer, assessed up to 19 weeks after start of treatment

• Pathological Complete Response Rate

  From treatment start date until the time of curative-intent surgery, approximately 8 weeks.

Study Arms (1)

Pembrolizumab with RT Boost

EXPERIMENTAL

Study drug plus "tumor boost" before standard of care treatment

Drug: Pembrolizumab; Radiation: RT Boost

Interventions

Pembrolizumab DRUG

checkpoint inhibitor

Also known as: Keytruda, MK-3475

Pembrolizumab with RT Boost

RT Boost RADIATION

The second dose of pembrolizumab will be given in conjunction with an RT boost, consisting of 8 Gy for 3 fractions.

Pembrolizumab with RT Boost

Eligibility Criteria

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

You may qualify if:

• Confirmed histologic diagnosis of invasive adenocarcinoma of the breast, and
• ER, PR and HER2 testing (on outside or Cedars-Sinai biopsy report), and
• High-risk, ER-positive and HER2-negative breast cancer patients. ER-positive disease is defined as ER\>10%, any PR and HER2-negative by ASCO CAP guidelines. High-risk disease will be defined by the presence of at least 2 of the following 3 criteria: histologic grade II-III, Ki-67 \> 20%, ER expression \< 75% by IHC)
• TNBC patients (defined as ER\<10%, PR\<10%, HER2-neu 0-1+ by IHC or FISH-negative; or as per MD discretion)
• Operable tumor measuring ≥2 cm in maximal diameter as measured by any available standard of care imaging (mammogram, breast ultrasound, breast MRI)
• Any nodal status
• Multifocal disease is permitted; largest focus must measure ≥2 cm
• Synchronous bilateral invasive breast cancer is permitted
• No indication of distant metastases
• Breast-conserving therapy is planned
• Tumor amenable to preoperative radiation therapy boost as determined by radiation oncologist
• ECOG performance status score of 0 or 1
• Screening laboratory values must meet the following criteria:
• i. White blood cells (WBCs) ≥ 2000/μL ii. Absolute neutrophil count (ANC) ≥ 1500/μL iii. Platelets ≥ 100 x 103/μL iv. Hemoglobin ≥ 11.0 g/dL v. Serum creatinine ≤ 2 mg/dL (or glomerular filtration rate ≥ 40 ml/min) vi. AST ≤ 2.5 x upper limit of normal (ULN) vii. ALT ≤ 2.5 x ULN viii. Total bilirubin within normal limits (except subjects with Gilbert's syndrome, who must have total bilirubin \< 3.0 mg/dL) ix. INR ≤ 1.5 x ULN unless participant is receiving anticoagulant therapy as long as PT or aPTT is within therapeutic range of intended use of anticoagulant(s) x. Negative HIV screening test xi. Negative screening tests for Hepatitis B and Hepatitis C. Patients with positive results that do not indicate true active or chronic infection may enroll after discussion and consensus agreement by the treating physician and principal investigator.
• Women of childbearing potential (WOCBP) must be using an acceptable method of contraception to avoid pregnancy throughout the study and for at least 4 months after the last dose of pembrolizumab in such a manner that the risk of pregnancy is minimized.

You may not qualify if:

• HER2-positive breast cancer defined as IHC3+ or IHC2+ with FISH\>2 AND copy number \>4 OR FISH \<2 AND copy number \>6
• Inflammatory breast cancer
• Contraindication(s) to breast-conserving therapy
• Contraindication to radiation therapy or planned partial breast irradiation
• Patients with cosmetic breast augmentations, specifically sub glandular implants with altered breast tissue, at the time of diagnosis
• Evidence of metastatic disease.
• Diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ (e.g. breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
• Medical history and concurrent diseases
• Active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• History of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
• Active infection requiring systemic therapy.
• Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results.
• Known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
• Known history of Hepatitis B (e.g., HBsAg reactive) or known active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).

Sponsors & Collaborators

• Stephen Shiao: lead
• United States Department of Defense: collaborator

Study Sites (1)

Cedars-Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Related Publications (1)

• Ho AY, Shiao S, Kobald SA, Chen J, Duda DG, Ly A, Bossuyt V, Cho HL, Arnold B, Knott S, Gupta GP, McAndrew P, Karlan S, Tighiouart M, Muzikansky A, Basho R, McArthur H. PEARL: A Phase Ib/II Biomarker Study of Adding Radiation Therapy to Pembrolizumab Before Neoadjuvant Chemotherapy in Human Epidermal Growth Factor Receptor 2-Negative Breast Cancer. J Clin Oncol. 2024 Dec 20;42(36):4282-4293. doi: 10.1200/JCO.24.00003. Epub 2024 Sep 19.

  PMID: 39298718 DERIVED

MeSH Terms

Conditions

Breast Neoplasms; Triple Negative Breast Neoplasms

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

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

Limitations and Caveats

Co-primary outcome for change in TILs is incomplete at the time of this results submission, as some TILs data not currently available. Current results for this outcome measure is reported according to current available data. Additional data may be reported at a later date.

Results Point of Contact

• Title: Stephen Shiao, MD, PhD
• Organization: Cedars-Sinai Medical Center

Stephen.Shiao@cshs.org

310-423-2836

Study Officials

• Stephen Shiao, MD, PHD

  Cedars-Sinai Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor of Radiation Oncology and Medicine

Model Details: Single Arm with Two Cohorts 1. Cohort 1: High-risk, ER-positive and HER2-negative breast cancer patients with primary tumors measuring at least 2cm 2. Cohort 2: TNBC patients with primary tumors measuring at least 2cm

Study Record Dates

• First Submitted: November 25, 2017
• First Posted: December 8, 2017
• Study Start: December 22, 2017
• Primary Completion: February 6, 2025
• Study Completion (Estimated): December 7, 2030
• Last Updated: April 20, 2026
• Results First Posted: April 28, 2023

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)