Testing the Addition of an Anti-cancer Drug, ASTX727 (Cedazuridine, Decitabine), to Chemotherapy (Paclitaxel) and Immunotherapy (Pembrolizumab) for Metastatic Triple-Negative Breast Cancer

NCT05673200 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2022-1081010546UM1CA186709
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 10

Brief Summary

This phase I trial tests the safety, side effects, and best dose of ASTX727 when given in combination with a usual approach of treatment with paclitaxel and pembrolizumab in patients with triple-negative breast cancer that has spread from where it first started (primary site) to other places in the body (metastatic). The usual approach is defined as care most people get for this type of cancer. The usual approach for patients with metastatic triple negative breast cancer who are not in a study is chemotherapy with drugs like paclitaxel, carboplatin, cisplatin, eribulin, vinorelbine, capecitabine, gemcitabine, doxorubicin or cyclophosphamide. There is a protein called PD-L1 that helps regulate the body's immune system. For patients who have PD-L1+ tumors, immunotherapy (pembrolizumab) is usually added to paclitaxel or carboplatin/gemcitabine as initial treatment. For patients who have PD-L1-negative tumors, chemotherapy alone is used, without immunotherapy. ASTX727 is a combination of two drugs, decitabine and cedazuridine. Cedazuridine is in a class of medications called cytidine deaminase inhibitors. It prevents the breakdown of decitabine, making it more available in the body so that decitabine will have a greater effect. Decitabine is in a class of medications called hypomethylation agents. It works by helping the bone marrow produce normal blood cells and by killing abnormal cells in the bone marrow. Paclitaxel is in a class of medications called antimicrotubule agents. It stops tumor cells from growing and dividing and may kill them. 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. Giving ASTX727 with usual treatment approach with paclitaxel and pembrolizumab may be able to shrink or stabilize the tumor for longer than the usual approach alone in patients with metastatic triple negative breast cancer.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• Maximally tolerated dose (MTD) of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase)

  Defined as the highest dose level among those under consideration where at most 1 of 6 patients develops a dose limiting toxicity and 2 or more of the 3-6 patients treated at the next higher dose level develop a dose limiting toxicity.

  Within the first cycle of treatment (28 days)

• Safety profile of ASTX727 in combination with paclitaxel and pembrolizumab (MK-3475) (Dose Finding Phase)

  The maximum grade of each type of toxicity will be recorded for each patient. For each toxicity reported by dose level, the percentage of patients developing any degree of that toxicity as well as the percentage of patients developing a severe degree (grade 3 or higher) will be determined.

  Up to 4 years

Secondary Outcomes (5)

• Tolerability (Dose Expansion Phase)

  Upon completion of the dose expansion phase

• Tumor response rate (Dose Expansion Phase)

  Up to 4 years

• Duration of response (Dose Expansion Phase)

  From the time measurement criteria are met for CR or PR until the first date that recurrent or progressive disease is objectively documented, assessed up to 4 years

• Overall survival (Dose Expansion Phase)

  From study entry to death due to any cause, assessed up to 4 years

• Progression-free survival (Dose Expansion Phase)

  From study entry to the documentation of disease progression, assessed up to 4 years

Study Arms (1)

Treatment (ASTX727, paclitaxel, pembrolizumab)

EXPERIMENTAL

Patients receive ASTX727 PO on days 1-5, 1-4, 1-3, or days 1, 3, and 5 of each cycle, and paclitaxel IV over 1 hour on days 1, 8, and 15 of each 28-day cycle or days 1 and 8 of each 21-day cycle. Cycles repeat every 21 or 28 days in the absence of disease progression or unacceptable toxicity. Patients also receive pembrolizumab IV over 30 minutes every 6 weeks (treatment day varies in 28-day cycles; day 1 of every odd 21-day cycle) in the absence of disease progression or unacceptable toxicity. Patients undergo collection of blood samples and CT and/or MRI throughout the trial. Patients in the dose-expansion phase also undergo a tumor biopsy during screening and day 1 of the treatment cycle 2 of the study.

Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Drug: Decitabine and Cedazuridine; Procedure: Magnetic Resonance Imaging; Drug: Paclitaxel; Biological: Pembrolizumab

Interventions

Biopsy Procedure PROCEDURE

Undergo biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Treatment (ASTX727, paclitaxel, pembrolizumab)

Biospecimen Collection PROCEDURE

Undergo collection of blood

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

Treatment (ASTX727, paclitaxel, pembrolizumab)

Computed Tomography PROCEDURE

Undergo CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (ASTX727, paclitaxel, pembrolizumab)

Decitabine and Cedazuridine DRUG

Given PO

Also known as: ASTX 727, ASTX-727, ASTX727, C-DEC, CDA Inhibitor E7727/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Combination Agent ASTX727, Cedazuridine/Decitabine Tablet, DEC-C, Inaqovi, Inqovi

Treatment (ASTX727, paclitaxel, pembrolizumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (ASTX727, paclitaxel, pembrolizumab)

Paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

Treatment (ASTX727, paclitaxel, pembrolizumab)

Pembrolizumab BIOLOGICAL

Given IV

Also known as: BCD-201, GME 751, GME751, Keytruda, Lambrolizumab, MK 3475, MK-3475, MK3475, Pembrolizumab Biosimilar BCD-201, Pembrolizumab Biosimilar GME751, Pembrolizumab Biosimilar QL2107, Pembrolizumab Biosimilar RPH-075, Pembrolizumab Biosimilar SB27, QL2107, RPH 075, RPH-075, RPH075, SB 27, SB-27, SB27, SCH 900475, SCH-900475, SCH900475

Treatment (ASTX727, paclitaxel, pembrolizumab)

Eligibility Criteria

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

You may qualify if:

• Patients must have histologically confirmed triple-negative breast cancer (TNBC) (estrogen receptor \[ER\] and progesterone receptor \[PR\] =\< 10%, human epidermal growth factor receptor-2 \[HER2\]-negative per American Society of Clinical Oncology \[ASCO\]/College of American Pathologists \[CAP\] guidelines) that is metastatic or unresectable
• Age \>= 18 years. Because no dosing or adverse event data are currently available on the use of ASTX727 in combination with pembrolizumab (MK-3475) and paclitaxel in patients \< 18 years of age, children are excluded from this study
• Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (or Karnofsky \>= 60%)
• Absolute neutrophil count (ANC) \>= 1500/mm\^3 (within 14 days prior to registration)
• Platelets \>= 100,000/mm\^3 (within 14 days prior to registration)
• Hemoglobin \>= 9 g/dL or \>= 5.6 mmol/L (within 14 days prior to registration)
• Criteria must be met without packed red blood cell (pRBC) transfusion within the prior 14 days of registration. Participants can be on stable dose of erythropoietin (90 days or more prior to registration)
• Creatinine clearance (CrCl) \>= 30 mL/min (within 14 days prior to registration)
• Glomerular filtration rate (GFR) can also be used in place of CrCl
• Total bilirubin =\< 1.5 x upper limit of normal (ULN) OR direct bilirubin =\< ULN for patients with total bilirubin levels \> 1.5 × ULN (within 14 days prior to registration)
• Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\]) and alanine aminotransferase (ALT) (serum glutamic-pyruvic transaminase \[SGPT\]) =\< 3 x institutional ULN (within 14 days prior to registration)
• For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
• Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
• Patients with treated brain metastases are eligible if there is evidence of measurable extracranial disease, and if follow-up brain imaging 4 weeks after central nervous system (CNS)-direct therapy shows no evidence of progression. Patients with carcinomatous meningitis are not eligible.
• Patients with a prior malignancy whose natural history does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial. Concurrent use of other antineoplastic treatments is not allowed.

You may not qualify if:

• Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within the 7 days prior to registration.
• Has a known additional malignancy that is progressing or requires active treatment.
• Has an active autoimmune disease that has required systemic treatment within 2 years prior to registration (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. Current treatment with systemic steroids up to 10 mg of prednisone daily or equivalent is allowed.
• Patients with uncontrolled intercurrent illness (including but not limited to interstitial lung disease or active, non-infectious pneumonitis) or a history of (non-infectious) pneumonitis that required steroids.
• History of grade 3-4 immediate hypersensitivity reaction to paclitaxel or other drugs formulated in polyoxyl 35 castor oil.
• Patients who are receiving any other investigational agents.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to ASTX727, pembrolizumab (MK-3475), and/or paclitaxel.
• Has a known history of active tuberculosis (TB).
• Gastrointestinal disorder that may impact absorption of oral medications.
• History of solid organ or bone marrow transplantation.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (10)

Mayo Clinic Hospital in Arizona

Phoenix, Arizona, 85054, United States

RECRUITING

UC Irvine Health Cancer Center-Newport

Costa Mesa, California, 92627, United States

RECRUITING

UC Irvine Health/Chao Family Comprehensive Cancer Center

Orange, California, 92868, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

TERMINATED

Mayo Clinic in Florida

Jacksonville, Florida, 32224-9980, United States

RECRUITING

Mayo Clinic in Rochester

Rochester, Minnesota, 55905, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

RECRUITING

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Triple Negative Breast Neoplasms

Interventions

Biopsy; Specimen Handling; decitabine and cedazuridine drug combination; Magnetic Resonance Spectroscopy; Paclitaxel; Taxes; pembrolizumab

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; Spectrum Analysis; Chemistry Techniques, Analytical; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations

Study Officials

• Roberto A Leon-Ferre

  Dana-Farber - Harvard Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 4, 2023
• First Posted: January 6, 2023
• Study Start: September 25, 2023
• Primary Completion (Estimated): February 23, 2027
• Study Completion (Estimated): February 23, 2027
• Last Updated: June 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (10)