Reinvigorating TNBC Response to Immunotherapy With Myeloid Inhibition and Radiation

What is the Purpose of this Study?

The purpose of this study is to examine the feasibility, safety, and effectiveness of an experimental combination therapy of the drug axatilimab, radiation to the tumor, and pembrolizumab (another drug) in patients who have been diagnosed with high-risk, triple negative breast cancer (TNBC). Researchers aim to determine whether this combination therapy may enhance the response to initial therapy. The study will evaluate whether the combination therapy increases the chance that patients will eliminate their cancer following treatment. Axatilimab is a special type of antibody produced in a laboratory. It works by blocking a specific protein receptor on immune cells to increase the effectiveness of the other treatments (pembrolizumab and radiation). Pembrolizumab is also an antibody produced in a laboratory and works to block a specific protein to strengthen the immune system. Researchers want to learn whether the combination treatment of drugs and radiation can help the body’s own immune system to fight and control cancer. The use of axatilimab and pembrolizumab in this study is investigational.

Eligibility

* Patients diagnosed with high-risk triple negative breast cancer (TNBC).
* 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%.

Inclusion Criteria:

* Patients diagnosed with high-risk triple negative breast cancer (TNBC).
* 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.
* Female ≥ 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 during the treatment period.

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.

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Where can I participate?

CS Cancer at Beverly Hills : Nikki Kem-Bernard
CS Cancer at Cedars-Sinai Medical Center : Nikki Kem-Bernard

More about this Clinical Trial

What is the full name of this clinical trial?

IIT2021-01-Shiao-CSF1Ri: METEORITE: Macrophage Targeting in Combination with Radiation and Pembrolizumab

Study Details

Disease Type/Condition

Breast

Principal Investigator

Shiao, Stephen

Co-Investigators

Amin Mirhadi, Anthony Nguyen, Cathie T Chung, Dorothy Park, Jin Sun Bitar, Julie Jang, Maryliza El-Masry, Michele Burnison, Mitchell Kamrava, Philomena McAndrew, Scott Karlan, Yuan Yuan

Age Group

Adult

Phase

IRB Number

STUDY00002225

ClinicalTrials.gov ID

NCT05491226

Key Eligibility

ClinicalTrials.gov

How do I learn more about this study?

Name

Nikki Kem-Bernard

Nikki.Bernard@cshs.org