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ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation | Clinical Trials | Clareo Health

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ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation

IIT2024-02-SHIAO-ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation

NCT07015853•Stephen Shiao

View on ClinicalTrials.gov

Summary

Open label, single-arm, prospective therapeutic trial. Pembrolizumab (MK-3475), 200 mg IV Q3W starting at C1D1/Week 1 for up to 2 years, until disease progression, or treatment intolerance. RT, 8 Gy x 3 fractions over 3 consecutive days at C1D8/Week 2; Axatilimab (SNDX-6352; INCA034176), 1 mg/kg, IV, Q2W starting 1 week post- RT C1D15/Week 3 until disease progression or treatment intolerance.

Detailed Description

Checkpoint blockade-mediated immunotherapy (IO) is an emerging cornerstone in the treatment of triple negative breast cancer (TNBC) in both the metastatic and curative intent settings. Initial studies of IO monotherapy in heavily pretreated metastatic TNBC were disappointing with low objective response rate (ORR) (5.3%: KEYNOTE-086, KEYNOTE-119) and no effect in OS (1-3). However, recent studies in patients with previously untreated metastatic TNBC, showed IO combinations with chemotherapy were associated with improved progression-free survival (PFS) and overall survival (OS) compared to chemotherapy alone in patients with "PD-L1 positive" disease (IMpassion130 and KEYNOTE-355) (4-7). Nonetheless, nearly half of patients on IMpassion130 had grade 3 or higher toxicity, leading to a discontinuation rate of 16.9%, and over 70% of all patients on first-line IO containing regimens will experience disease progression within one year. Based on these data, IO-containing regimens have become the standard-of-care treatment option for metastatic TNBC, albeit with a high failure rate and a non-trivial toxicity profile. Second line antibody-drug conjugate Sacituzumab govitecan while also improving response in metastatic TNBC still has 85% of patients fail at 1 year (ASCENT, Bardia NEJM 2021). Therefore, novel strategies that augment IO-enhanced tumor-specific responses and limit treatment-associated toxicities are critically important in TNBC. Lastly, radiotherapy (RT), commonly used in palliation of metastatic TNBC, is a potent modulator of the immune response, and can produce responses in unirradiated tumors in combination with IO (8-11).

Eligibility

Age

18 - No limit years

Sex

ALL

Healthy Volunteers

Inclusion Criteria

•Age ≥ 18 years at the time of consent.
•Patients with metastatic or locally recurrent TNBC who received prior immunotherapy in any setting (curative or advanced/metastatic).
•Histologically or cytologically-confirmed TNBC, defined as ER \<10%, PR \<10%, HER2-negative by ASCO CAP guidelines. Note: HER2 0-2+ IHC is allowed (i.e., if FISH-negative, this is still considered HER2-negative).
•ECOG Performance Status ≤ 1.
•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 for eligibility verification.
•Female subjects of childbearing potential should be willing to use highly effective contraceptive methods (Appendix 12.6) 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.
•Male participants should be willing to use highly effective contraceptive methods (Appendix 12.6) during the treatment period through 120 days after the last dose of study treatment and refrain from donating sperm during this period.
•Written informed consent obtained from subject and ability for subject to comply with the requirements of the study.

Exclusion Criteria

•Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose 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 chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) 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).
•Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
•Has had prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study treatment Day 1 or who has not recovered (i.e., \> Grade 1 or 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 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 is progressing or has required treatment within the last 5 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
•Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least four weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
•Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.).
+14 more criteria

Locations (1)

Cedars-Sinai Medical Center

Los Angeles, California, United States

Key Dates

Start Date

September 1, 2025

Primary Completion Date

December 1, 2032

Completion Date

December 1, 2032

Last Updated

August 27, 2025

Enrollment

ESTIMATED participants

Conditions

TNBC - Triple-Negative Breast CancerBreast Cancer

Interventions

Pembrolizumab

DRUG

Radiotherapy

RADIATION

Axatilimab

DRUG

Contacts

Clinical Trial Navigator

CONTACT

3104232133 cancer.trial.info@cshs.org

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Data Source & Attribution

This clinical trial information is sourced from ClinicalTrials.gov, a service of the U.S. National Institutes of Health.

ClinicalTrials.gov last update: August 27, 2025Data synced to Clareo: March 29, 2026

Modifications: This data has been reformatted for display purposes. Eligibility criteria have been parsed into inclusion/exclusion sections. Location data has been geocoded to enable distance-based search. For the authoritative and most current information, please visit ClinicalTrials.gov.

Neither the United States Government nor Clareo Health make any warranties regarding the data. Check ClinicalTrials.gov frequently for updates.

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ASTRAEA: ReinvigorAting ReSponse To ImmunotheRApy in MEtAstatic TNBC With Combination Myeloid Inhibition and Radiation

Inclusion Criteria

Exclusion Criteria

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