Propranolol and Pembrolizumab for Tumor Re-sensitization and Treatment of Patients With Checkpoint Inhibitor Refractory Metastatic or Unresectable Triple Negative Breast Cancer

NCT05741164 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 5 other identifiers: STUDY00009637NCI-2026-00570I 2612022K08CA279766WINSHIP6621-25
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 2

Brief Summary

This phase II trial tests how well propranolol and pembrolizumab work to cause tumor re-sensitization and therefore treatment in patients with triple negative breast cancer that has not responded to previous checkpoint inhibitor therapy (refractory), cannot be removed by surgery (unresectable) or has spread from where it first started (primary site) to other places in the body (metastatic). Propranolol is a drug that is classified as a beta-blocker. Beta-blockers affect the heart and circulation. Beta-blockers, like propranolol, may help to counteract effects of certain stress hormones produced by the body during cancer treatment and may increase the effectiveness of the pembrolizumab. Pembrolizumab is a drug that is classified as an immune checkpoint inhibitor. 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. Propranolol may be able to re-sensitize the cells of the immune system to respond to the checkpoint inhibitor pembrolizumab in patients with checkpoint inhibitor refractory metastatic or unresectable triple negative breast cancer.

Conditions

Metastatic Triple-Negative Breast Carcinoma; Refractory Triple-Negative Breast Carcinoma; Anatomic Stage III Breast Cancer AJCC v8; Anatomic Stage IV Breast Cancer AJCC v8; Unresectable Triple-Negative Breast Carcinoma

Outcome Measures

Primary Outcomes (1)

• Objective response

  Efficacy as determined by immune-related Response Evaluation Criteria in Solid Tumors (irRECIST). Will be summarized using frequencies and relative frequencies. The best response within the first 6 months will be determined as the best objective response.

  Up to 6 months

Secondary Outcomes (3)

• Progression free survival

  The time treatment initiation until disease progression (per irRECIST), death due to any cause, subsequent therapies (treated as censored), or last follow-up, assessed up to 6 months

• Overall survival

  The time from treatment initiation until death due to any cause or last follow-up, assessed up to 6 months

• Incidence of adverse events of propranolol when given in combination with pembrolizumab

  Up to 2 years

Study Arms (1)

Treatment (propranolol and pembrolizumab)

EXPERIMENTAL

Patients receive propranolol PO and pembrolizumab IV while on study. Patients undergo CT scan, blood sample collection and may undergo tumor biopsy during screening and on study.

Procedure: Biopsy; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Pembrolizumab; Drug: Propranolol; Other: Questionnaire Administration

Interventions

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized Tomography, CT, CT Scan, tomography

Treatment (propranolol and pembrolizumab)

Propranolol DRUG

Given PO

Also known as: 1-[(1-Methylethyl)amino]-3-(1-naphthalenyloxy)-2-propanol

Treatment (propranolol and pembrolizumab)

Questionnaire Administration OTHER

Ancillary studies

Treatment (propranolol and pembrolizumab)

Biopsy PROCEDURE

Undergo tumor biopsy

Also known as: BIOPSY_TYPE, Bx

Treatment (propranolol and pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo blood sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (propranolol and pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: Keytruda, Lambrolizumab, MK-3475, SCH 900475

Treatment (propranolol and pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Age \>= 18 years of age
• Have pathologically confirmed diagnosis of unresectable or metastatic triple negative breast cancer (TNBC) with no curative treatment options
• No chemotherapy, radiotherapy, or major surgery within 4 weeks of protocol treatment
• Checkpoint inhibitor refractory patients (i.e., no longer responding to chemotherapy and checkpoint inhibitor) who have disease progression on prior line of chemotherapy and pembrolizumab, and, who in the opinion of the physician, can continue checkpoint inhibitor
• Patients must be agreeable to pre- and 6-week post treatment biopsy in part 1 of the study
• The pre-treatment biopsy for this study must be taken at least 4 weeks after all previous chemotherapy (pembrolizumab is allowed during this period)
• Participants of child-bearing potential must agree to use adequate contraceptive methods (e.g. hormonal or barrier method of birth control; abstinence) prior to study entry. 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
• Have an Eastern Cooperative Oncology Group (ECOG) Performance Status of =\< 1
• Platelets \>= 100,000/uL
• Hemoglobin \>= 9.0 g/dL
• Absolute neutrophil count (ANC) \>= 1500/uL
• Total bilirubin =\< institutional upper limit of normal (ULN)
• Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) =\< 2.5 X institutional ULN
• Creatinine clearance \>= 50 mL/min per Cockcroft-Gault equation
• HbA1C \<=8.5

You may not qualify if:

• Patients currently treated with systemic immunosuppressive agents, including steroids, are ineligible until 3 weeks after removal from immunosuppressive treatment
• Patients with active autoimmune disease, requiring ongoing immunosuppressive therapy or history of transplantation
• Patients with rapidly progressive disease/ symptomatic disease
• Patients with primary resistance (i.e., did not respond to initial treatment with chemotherapy plus checkpoint inhibitor) with progressive disease at 12 weeks after starting chemotherapy and pembrolizumab
• Patients who are pregnant or nursing. Women of childbearing potential (WOCBP) will have to undergo a urine pregnancy test as part of screening
• Participants with symptomatic known brain metastases \< 4 weeks from radiation treatment should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other adverse events
• History of malignancy other than breast cancer within 5 years prior to screening, with the exception of those with a negligible risk of metastases or death
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
• Unwilling or unable to follow protocol requirements
• Contraindications to the use of beta-blockers, like: uncontrolled depression, unstable angina pectoris, uncontrolled heart failure (grade III or IV), hypotension (systolic blood pressure \< 100 mmHg), severe asthma or chronic obstructive pulmonary disease (COPD), uncontrolled type I or type II diabetes mellitus (hemoglobin A1C \[HbA1C\] \> 8.5 or fasting plasma glucose \> 160 mg/dl at screening), symptomatic peripheral arterial disease or Raynaud's syndrome, untreated pheochromocytoma, current use of beta-blockers or non-dihydropyridine calcium channel blockers
• Any additional condition which in the investigator's opinion deems the participant an unsuitable candidate to receive the study drugs

Sponsors & Collaborators

• Emory University: lead
• National Cancer Institute (NCI): collaborator

Study Sites (2)

Emory University Hospital

Atlanta, Georgia, 30322, United States

Location

Roswell Park Cancer Institute

Buffalo, New York, 14263, United States

Location

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Specimen Handling; pembrolizumab; Propranolol

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Study Officials

• Shipra Gandhi, MD, MS

  Emory University Hospital/Winship Cancer Institute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Shipra Gandhi, MD, MS

CONTACT

404-778-1900; shipra.gandhi@emory.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: February 14, 2023
• First Posted: February 23, 2023
• Study Start: March 30, 2026
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): November 30, 2028
• Last Updated: February 17, 2026

Record last verified: 2026-02

Locations

US (2)