A Study of Pembrolizumab and Ablation (Cryoablation or Histotripsy) in People With Breast Cancer

Does Ablation (Cryoablation or Histotripsy) Boost Immune Response Improving the Benefits of Pembrolizumab in Patients With Metastatic or Locally Advanced Triple Negative Breast Cancer?

Participants will have a confirmed diagnosis of metastatic breast cancer and will receive pembrolizumab in combination with ablation (cryoablation or histotripsy) OR pembrolizumab alone. Participants will be randomly assigned.

Study Overview

• Status: Recruiting
• Conditions: Breast Cancer; Metastatic Breast Cancer; Triple Negative Breast Cancer; Triple Negative Breast Neoplasms; Breast Cancer Stage IV; Locally Advanced Breast Cancer; Metastatic Triple-Negative Breast Carcinoma; Locally Advanced Triple-Negative Breast Carcinoma
• Intervention / Treatment: Drug: Pembrolizumab; Device: Cryoablation; Device: Histotripsy

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Yolanda Bryce, MD; Phone Number: 212-639-6530; Email: brycey@mskcc.org
• Study Contact Backup: Name: Larry Norton, MD; Phone Number: 646-888-5319; Email: nortonl@MSKCC.ORG

Study Locations

• United States
  • New Jersey
    • Basking Ridge, New Jersey, United States, 07920
      • Recruiting
      • Memorial Sloan Kettering Cancer Center at Basking Ridge (Limited Protocol Activities)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
    • Middletown, New Jersey, United States, 07748
      • Recruiting
      • Memorial Sloan Kettering Monmouth (Limited Protocol Activities)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
    • Montvale, New Jersey, United States, 07645
      • Recruiting
      • Memorial Sloan Kettering Bergen (Limited Protocol Activities)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
  • New York
    • Commack, New York, United States, 11725
      • Recruiting
      • Memorial Sloan Kettering Suffolk-Commack (Limited Protocol Activities )
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
    • Harrison, New York, United States, 10604
      • Recruiting
      • Memorial Sloan Kettering Westchester (Limited Protocol Activities)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
    • New York, New York, United States, 10065
      • Recruiting
      • Memorial Sloan Kettering Cancer Center (All protocol activites)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530
    • Rockville Centre, New York, United States, 11553
      • Recruiting
      • Memorial Sloan Kettering Nassau (Limited Protocol Activites)
      • Contact: Yolanda Bryce, MD; Phone Number: 212-639-6530

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients ≥ 18 years of age
• Confirmed histologic diagnosis of metastatic TNBC or locally advanced inoperable TNBC
• 1 site amenable cryoablation of at least 1.5 cm in size as determined by an Interventional Radiologist. Eligible cryoablation sites include (but not limited to) soft tissue, liver, lung, and bone as determined by an Interventional Radiologist to be safest and most feasible.
• Physically fit (clinically eligible) to undergo ablation as per usual clinical practice
• Per clinical guidelines, women of childbearing age should use effective contraception during treatment with pembrolizumab and for at least 4 months after the last dose of the drug, which will be assessed and monitored by, and the responsibility of, the patient's medical oncologist (not study investigators or research team) as pembrolizumab is standard of care. Memorial Sloan Kettering Cancer Center Pregnancy Standards will be followed prior to ablation. That is, female patients that are 11-50 years of age and of childbearing potential will undergo a pregnancy test within 2 weeks (15 days) before ablation. Pregnancy test will not be required in patients with bilateral oophorectomy, bilateral salpingectomy, bilateral salpingectomy-oophorectomy, hysterectomy, menopause (no menses ≥ 1 year prior to treatment or after completion of all treatment), or surgical sterilization (i.e. tubal ligation or blockage), with documentation of permanent exemptions in CIS ("Pregnancy Testing Exemption").

• Pembrolizumab therapy (200 mg every 3 weeks) planned as part of standard of care as first, second, or third line of therapy

  • Eligible for PD-1 inhibitor per the patient's medical oncologist, with planned treatment with PD-1 inhibitor per the patient's medical oncologist. Additional systemic therapy is per the patient's medical oncologist. The following systemic therapy will be accepted (the timing of the systemic therapy relative to pembrolizumab and ablation is not restricted):

    • Capecitabine (Xeloda, available as a generic drug)
    • Carboplatin (Paraplatin, available as a generic drug)
    • Cisplatin (Platinol, available as a generic drug)
    • Cyclophosphamide (Cytoxan, available as a generic drug)
    • Docetaxel (Taxotere)
    • Doxorubicin (Adriamycin, available as a generic drug)
    • Pegylated liposomal doxorubicin (Doxil)
    • Epirubicin (Ellence, available as a generic drug)
    • Eribulin (Halaven)
    • Fluorouracil (5-FU, Adrucil, available as a generic drug)
    • Gemcitabine (Gemzar, available as a generic drug)
    • Ixabepilone (Ixempra)
    • Methotrexate (available as a general drug)
    • Nab-paclitaxel (Abraxane)
    • Paclitaxel (Taxol, available as a generic drug)
    • Vinorelbine (Navelbine, available as a generic drug)

Exclusion Criteria:

• Patient not eligible for PD-1 inhibitor per the patient's medical oncologist
• No disease amenable for ablation
• Pembrolizumab therapy not planned as part of standard of care

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pembrolizumab + Ablation (Cryoablation or Histotripsy); Participants will have a diagnosis of metastatic triple negative breast cancer or locally advanced inoperable triple negative breast cancer. Participants will be randomized 2 (ablation arm): 1 (no ablation arm).	Drug: Pembrolizumab; Participants will receive Pembrolizumab as part of standard of care treatment.; Device: Cryoablation; Cryoablation is a type of thermal ablation that is a minimally invasive alternative technique to surgical resection.; Device: Histotripsy; Histotripsy of the liver is a noninvasive, nonthermal ablation technique that employs high intensity focused ultrasound pulses to mechanically disrupt targeted hepatic tissues- typically liver tumors-via a process known as acoustic cavitation.
Active Comparator: Pembrolizumab; Participants will have a diagnosis of metastatic triple negative breast cancer or locally advanced inoperable triple negative breast cancer. Participants will be randomized 2 (ablation arm): 1 (no ablation arm).	Drug: Pembrolizumab; Participants will receive Pembrolizumab as part of standard of care treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in CD4-PD1 from baseline to post-ablation	Assess changes in CD4-PD1 in the blood after ablation in patients with metastatic or locally advanced triple negative breast cancer (TNBC).	6 weeks after cryoablation

Collaborators and Investigators

• Sponsor: Memorial Sloan Kettering Cancer Center
• Investigators: Principal Investigator: Yolanda Bryce, MD, Memorial Sloan Kettering Cancer Center

Publications and helpful links

Helpful Links

• Memorial Sloan Kettering Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): January 29, 2024
• Primary Completion (Estimated): January 29, 2027
• Study Completion (Estimated): January 29, 2027

Study Registration Dates

• First Submitted: January 30, 2024
• First Submitted That Met QC Criteria: January 30, 2024
• First Posted (Actual): February 7, 2024

Study Record Updates

• Last Update Posted (Actual): September 14, 2026
• Last Update Submitted That Met QC Criteria: September 9, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: breast cancer; Memorial Sloan Kettering Cancer Center; pembrolizumab; metastatic breast cancer; triple negative breast cancer; cryoablation; locally advanced breast cancer; metastatic TNBC; breast cancer stage IV; metastatic triple negative breast carcinoma; 23-390; locally advanced triple negative breast carcinoma; locally advanced triple negative breast cancer
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Skin and Connective Tissue Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Surgical Procedures, Operative; Ablation Techniques; pembrolizumab; Cryosurgery
• Other Study ID Numbers: 23-390

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes