Pembrolizumab in Treating Patients With Stage IV Metastatic or Recurrent Inflammatory Breast Cancer or Triple-Negative Breast Cancer Who Have Achieved Clinical Response or Stable Disease to Prior Chemotherapy

A Phase II Study of Anti-PD-1 (MK-3475) Therapy in Patients With Metastatic Inflammatory Breast Cancer (IBC) or Non-IBC Triple Negative Breast Cancer (TNBC) Who Have Achieved Clinical Response or Stable Disease to Prior Chemotherapy

This phase II trial studies how well pembrolizumab works in treating patients with stage IV inflammatory breast cancer or triple-negative breast cancer that has spread to other places in the body (metastatic) or has come back (recurrent), and who have achieved clinical response or stable disease to prior chemotherapy. 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.

Study Overview

• Status: Active, not recruiting
• Conditions: Edema; Erythema; Estrogen Receptor Negative; HER2/Neu Negative; Progesterone Receptor Negative; Triple-Negative Breast Carcinoma; Recurrent Inflammatory Breast Carcinoma; Stage IV Inflammatory Breast Carcinoma; Peau d'Orange
• Intervention / Treatment: Other: Laboratory Biomarker Analysis; Biological: Pembrolizumab

Detailed Description

PRIMARY OBJECTIVES:

Primary Objective: To assess the efficacy of MK-3475 as a single agent in patients with metastatic IBC or non-IBC TNBC

EXPLORATORY OBJECTIVES:

1. To investigate the association between biomarkers in the peripheral blood and tumor tissue, such as PD-L1 expression, with safety and efficacy for IBC or non-IBC TNBC patients treated with MK-3475.
2. To determine the disease control rate of metastatic IBC or non-IBC TNBC patients who have achieved clinical response or stable disease to the systemic therapy.
3. To investigate the association between biomarkers and efficacy by RNA-sequencing of exosomes in blood and tumor for IBC or non-IBC TNBC patients treated with MK-3475.
4. To investigate the 5-year OS for IBC or non-IBC TNBC patients treated with MK-3475

OUTLINE:

Patients receive pembrolizumab 200mg IV over approximately 30 minutes on day 1. Cycles repeat every 21 days for 8 cycles and then pembrolizumab 400mg IV every 42 days for total up to 24 months in the absence of disease progression or unacceptable toxicity

After completion of study treatment, patients are followed up at approximately 1 and 3 months.

• Study Type: Interventional
• Enrollment (Actual): 71
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Texas
    • Houston, Texas, United States, 77030
      • M D Anderson Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Is willing and able to provide written informed consent for the trial
• Is a female or male and >/= 18 years of age
• Has histological confirmation of HER2 normal breast carcinoma with a clinical diagnosis of IBC based on presence of inflammatory changes in the involved breast, including diffuse erythema and edema (peau d'orange), with or without an underlying palpable mass involving the majority of the skin of the breast; pathological evidence of dermal lymphatic invasion should be noted but is not required for diagnosis of inflammatory breast cancer regardless estrogen receptor (ER)/progesterone receptor (PR) status; OR has histological confirmation of triple negative breast carcinoma (HER2 normal, ER/PR < 10%) without clinical diagnosis of IBC
• Has stage IV or recurrent disease that has been treated
• Has clinical response or stable disease for minimum of two months (three cycles of every three week chemotherapy or 8 weeks of weekly regimen, etc.) after receiving any prior chemotherapy for metastatic/recurrent disease; a minimum of two cycles (6-8 weeks) of chemotherapy is required to determine clinical response.

Per RECIST criteria 1.1, Clinical response for measurable disease is defined as complete response (CR) or partial response (PR); for non-measurable disease only (i.e. bone metastasis, ascites, pleural effusion, and pathological lymph nodes >/= 10 to <15 mm short axis) is defined as persistence of one or more non-target lesion(s) and no increase in overall tumor burden.

• Is HER2 normal, defined as HER2 0 or 1+ by IHC and negative by FISH if performed; or HER2 is 2+ by IHC and negative by FISH; or HER2 negative by FISH if IHC is not performed.
• Has a performance status of 0-1 on the Eastern Cooperative Oncology Group (ECOG) performance scale
• Has adequate organ function as determined by the following laboratory values:

ANC >/= 1000 /mcL, Platelets >/=100,000 /mcL, Hgb >/= 9 g/dL, creatinine levels < 1.5 x ULN, Total bilirubin </= 1.5 x ULN, ALT and AST </= 2.5 x ULN or </=5 x ULN for participants with liver metastases.

• Participants of childbearing potential should be willing to use effective methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through at least 4 months after the last dose of study drug. Participants of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year. Effective methods of birth control include 1). Use of hormonal birth control methods: pills, shots/injections, implants (placed under the skin by a health care provider), or patches (placed on the skin); 2).Intrauterine devices (IUDs); 3).Using 2 barrier methods (each partner must use 1 barrier method) with a spermicide. Males must use the male condom (latex or other synthetic material) with spermicide. Females must choose either a Diaphragm with spermicide, or Cervical cap with spermicide, or a sponge (spermicide is already in the contraceptive sponge).
• Has negative serum or urine pregnancy test for participants of childbearing potential

Exclusion Criteria:

• Is currently participating in a study of an investigational anti-cancer agent
• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy
• Has not recovered from adverse events due to prior therapies, i.e. monoclonal antibody, chemotherapy, targeted small molecule therapy, radiation therapy, or surgery. (Note: Participants with ≤ grade 2 neuropathy, alopecia and general disorders and administration site conditions [per Common Terminology Criteria for Adverse Events (CTCAE version 4.0) are an exception to this criterion and may qualify for the study)
• Has a known malignancy (other than breast cancer) except basal cell carcinoma or squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
• Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis; participants with previously treated brain metastases may participate if they are stable, and have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment
• Has an active autoimmune disease requiring systemic treatment within the past 3 months or a documented history of clinically severe autoimmune disease, or a syndrome that requires systemic steroids or immunosuppressive agents; participants with vitiligo or resolved childhood asthma/atopy would be an exception to this rule. Participants that require intermittent use of bronchodilators or local steroid injections would not be excluded from the study. Participants with hypothyroidism stable on hormone replacement or Sjogren's syndrome will not be excluded from the study.
• Has a history of (non-infectious) pneumonitis that required steroids or current pneumonitis
• Has an active infection requiring systemic therapy
• Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
• Has a known history of human immunodeficiency virus (HIV)
• Has a known active hepatitis B or hepatitis C
• Have received a live vaccine within 30 days prior to the first dose of trial treatment
• Is receiving concurrent anti-cancer therapy for metastatic disease

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment (pembrolizumab); Patients receive pembrolizumab 200mg IV over approximately 30 minutes on day 1. Cycles repeat every 21 days for 8 cycles and then pembrolizumab 400mg IV every 42 days for total up to 24 months in the absence of disease progression or unacceptable toxicity	Other: Laboratory Biomarker Analysis; Correlative studies; Biological: Pembrolizumab; Given IV; Other Names: Keytruda; MK-3475; Lambrolizumab; SCH 900475

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To Assess the Efficacy of Pembrolizumab as a Single Agent in Patients With Metastatic IBC or Non-IBC TNBC	The disease control rate (DCR) was assessed. The DCR was defined as the proportion of all treated patients with a lack of progression within 4 months as determined by radiologic imaging or clinical assessment.	4 months from the start of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Biomarker analyses	Correlation among biomarkers at baseline in each specimen and between different specimens will be assessed. The association among various continuous and discrete biomarkers or disease status groups will be assessed by the exploratory data analysis using scatter plot matrix, box plots, BLiP plot and trellis plot, etc, and may be tested by t-test/analysis of variance/Wilcoxon rank sun test/Kruskal-Wallis test, whichever is appropriate. Correlation between continuous biomarkers will be examined by Pearson or Spearman rank correlation coefficients.	Baseline
Disease control survival	Estimated using Kaplan-Meier method.	Up to 3 months post-treatment
Overall survival time	Estimated using Kaplan-Meier method.	Up to 3 months post-treatment

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation Between PD-L1 IHC Status and Overall Survival in Patients Treated With Pembrolizumab	PD-L1 satus in tumor tissue was determined by IHC analysis: positive CPS≥ 10, negative CPS <10. Median OS and 95% confidence interval are estimated by the PD-L1 status in tumor tissue (positive vs. negative).	From the first dose of pembrolizumab up to 5 years
Correlation Between PD-L1 IHC Status and Progression-Free Survival in Patients Treated With Pembrolizumab	PD-L1 expression in tumor tissue was assessed by immunohistochemistry (IHC), with CPS ≥10 defined as PD-L1 positive and CPS <10 as PD-L1 negative.Median PFS and 95% confidence interval are estimated by the PD-L1 status in tumor tissue (positive vs. negative).	From the first dose of pembrolizumab up to 3 years
To Investigate the Association Between Biomarkers and Efficacy by RNA-sequencing of Exosomes in Blood and Tumor for IBC or Non-IBC TNBC Patients Treated With Pembrolizumab.	RNA-sequencing will be performed with RNA extracted from plasma at baseline.	Baseline
Overall Survival for IBC or Non-IBC TNBC Patients Treated With Pembrolizumab	Overall survival time from the registration date was estimated using Kaplan-Meier method.	From registration date to up to 5 years

Collaborators and Investigators

• Sponsor: M.D. Anderson Cancer Center
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Bora Lim, MD, M.D. Anderson Cancer Center

Publications and helpful links

Helpful Links

• MD Anderson Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): June 11, 2015
• Primary Completion (Actual): June 15, 2024
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: April 3, 2015
• First Submitted That Met QC Criteria: April 3, 2015
• First Posted (Estimated): April 8, 2015

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 5, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Manifestations; Skin Diseases; Breast Diseases; Breast Neoplasms; Pathological Conditions, Signs and Symptoms; Skin and Connective Tissue Diseases; Signs and Symptoms; Triple Negative Breast Neoplasms; Edema; Inflammatory Breast Neoplasms; Erythema; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; pembrolizumab
• Other Study ID Numbers: 2014-0533 (Other Identifier: M D Anderson Cancer Center); NCI-2015-00671 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No