Recruiting

Phase 2

Pembrolizumab, Radiation & CSF-1R InhibitionReinvigorating TNBC Response to Immunotherapy With Combination Myeloid Inhibition and Radiation

Sponsor:

Stephen Shiao

Code:

NCT05491226

Conditions

TNBC - Triple-Negative Breast Cancer

Breast Cancer

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Pembrolizumab

Radiation Therapy

Axatilimab

Study Details

Brief summary:

This is an open-label prospective, single institution, Phase II study of pembrolizumab in combination with radiation therapy and CSF-1R inhibition in patients with high-risk TNBC. The primary objective is to assess the pathologic complete response (pCR) rate where pCR is defined as the absence of invasive disease in the breast and lymph nodes at the time of standard of care (SOC) treatment. Secondary objectives include evaluating the change in tumor infiltrating lymphocytes (TILs), safety and tolerability of the combination, progression-free survival, event-free survival, overall survival, and node clearance.

Conditions

TNBC - Triple-Negative Breast Cancer

Breast Cancer

Study ID

NCT05491226

Start date

Nov 17, 2023

Status verified date

Apr, 2026

Completion date

Dec 1, 2026

Anticipated

Primary completion date

Dec 1, 2026

Anticipated

Eligibility Criteria

Sex: Female

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

Female patients diagnosed with high-risk triple negative breast cancer (TNBC) with intent for neoadjuvant therapy.
Low tumor-infiltrating lymphocyte (TIL) score, defined as stromal TIL (sTIL) ≤40%; or node-positive; or combined positive score (CPS) < 10 or PD-L1 tumor positivity <1%.
Written informed consent obtained from subject and ability for subject to comply with the requirements of the study, including consent for research blood draws and use of available archived tissue.
Age ≥ 18 years of age on day of signing informed consent.
Histologically or cytologically-confirmed TNBC (defined as ER <1%, PR<1%, her-2-neu 0-1+ by IHC or FISH-negative).
If an archived tumor tissue is unavailable, be willing to provide tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 6 weeks (42 days) prior to initiation of treatment on Day 1 of RT.
Have a performance status of 0 or 1 on the ECOG Performance Scale.
Demonstrate adequate organ function.
Female subject of childbearing potential should have a negative serum or urine pregnancy test or documentation of absence of pregnancy by a gynecologist within 14 days of initiating first dose of pembrolizumab (1 week lead-in) for eligibility verification.
Female subjects of childbearing potential should be willing to comply to the contraceptive guidance in Appendix 12.2 during the treatment period through 120 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year.

Exclusion Criteria:

Evidence of metastatic disease.
Has received prior radiotherapy within 2 weeks of start of study intervention.
Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
Has a known history of active TB (Bacillus Tuberculosis).
Hypersensitivity to pembrolizumab or any of its excipients.
Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or who has not recovered (i.e., > Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
Has had prior chemotherapy or targeted small molecule therapy within 2 weeks prior to study Day 1 or who has not recovered (i.e., > Grade 1 or at baseline) from adverse events due to a previously administered agent. Note: Subjects with ≤ Grade 2 neuropathy are an exception to this criterion and may qualify for the study.
Has a known additional malignancy that progressed or required treatment in the last 5 years. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain parenchymal metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis, which is excluded regardless of clinical stability.
Has 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
Has known history of/active, non-infectious pneumonitis requiring treatment with steroids or has history of/active interstitial lung disease.
Has an active infection requiring systemic therapy.
Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
Is pregnant or breastfeeding, or expecting to conceive within the projected duration of the trial, starting with the pre-screening or screening visit through 120 days after the last dose of trial treatment. A WOCBP who has a positive urine pregnancy test within 2 weeks prior to start of study treatment (first dose of pembrolizumab). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. Note: Negative urine or serum pregnancy test is also conducted within 72 hours prior to C1D1 for study procedures but if screening pregnancy test is done within 72 hours of C1D1, it is not required to be repeated..
Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
Has a known history of active Hepatitis B (e.g., HBsAg reactive) or known active Hepatitis C (e.g., HCV RNA \[qualitative\] is detected).
Has received a live vaccine or live-attenuated vaccine within 30 days of planned start of pembrolizumab. Administration of killed vaccines is allowed.
Has had an allogenic tissue/solid organ transplant.

Study Design

Enrollment

35 participants

Anticipated

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pembrolizumab with Radiation Therapy and Axatilimab

Interventions

Pembrolizumab

Pembrolizumab 200 mg is administered intravenously at Week 1, then every 3 weeks during the treatment period (6 weeks). Therapy will continue for until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.

Radiation Therapy

Radiation therapy (RT) consists of 8 Gy for 3 fractions over 3 consecutive days at Week 2.

Axatilimab

Axatilimab 1 mg/kg is administered intravenously weekly starting 1 week post- RT (Week 3). Therapy will continue until initiation of SOC curative-intent treatment (neoadjuvant chemo therapy or surgery) at Week 7.

Primary outcome measure

Pathological complete response (pCR) rate. [ Time Frame: From treatment start date until the time of curative-intent treatment, approximately 7 weeks. ]

Central Contacts and Locations

Central contacts

Clinical Trial Recruitment Navigator

310-423-2133 cancer.trial.info@cshs.org

Locations

Cedars-Sinai Medical Center

Recruiting

Los Angeles, California, United States, 90048

Contacts

Clinical Trial Recruitment Navigator

cancer.trial.info@cshs.org

More Information

Sponsor

Stephen Shiao

Last update posted

Apr 20, 2026

Last verified

Apr, 2026

Keywords

pembrolizumab
axatilimab
radiation therapy

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Stephen Shiao on 2026-04-20.