Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.
Inclusion Criteria:
- 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 of registration)
- Platelets >= 100,000/mm^3 (within 14 days of registration)
- Hemoglobin >= 9 g/dL or >= 5.6 mmol/L(within 14 days of registration)
- Criteria must be met without packed red blood cell (pRBC) transfusion within the
prior 2 weeks. Participants can be on stable dose of erythropoietin (>=
approximately 3 months).
- Creatinine clearance (CrCl) >= 30 mL/min (within 14 days of 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 of 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 of 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.
- Patients should be New York Heart Association Functional Classification of class II or
better.
- Patients who have received live attenuated vaccines within 30 days of registration are
not eligible. Seasonal flu vaccines that do not contain live virus, and coronavirus
disease 2019 (COVID-19) vaccinations and boosters are permitted.
- Patients with prior history of peripheral neuropathy are allowed if it has recovered
to grade 1 or less.
- Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral
therapy with undetectable viral load within 6 months of registration are eligible for
this trial.
- Any number of prior lines in the metastatic setting. Patients who have received prior
PD-1/PD-L1 monoclonal antibodies in any disease setting are eligible.
- For enrollment to Dose Finding Cohort: Availability and willingness to provide
archival tumor tissue as required per protocol.
- For enrollment to Dose Expansion Cohort: (i) Willingness to provide baseline and
3-week tumor tissue biopsy specimens. (ii) Patients must have a measurable disease per
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.
- The effects of ASTX727 and pembrolizumab (MK-3475) on the developing human fetus are
unknown. For this reason and because these agents as well as other therapeutic agents
used in this trial are known to be teratogenic, women of child-bearing potential and
men must agree to use adequate contraception (hormonal or barrier method of birth
control; abstinence) prior to study entry, for the duration of study participation,
and 180 days after the last dose of study treatment. 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. Pregnant women are excluded from
this study because pembrolizumab (MK-3475) is an anti PD-1 monoclonal antibody agent,
ASTX727 is a hypomethylating agent, and paclitaxel is a class D agent with the
potential for teratogenic or abortifacient effects. Because there is an unknown but
potential risk for adverse events in nursing infants secondary to treatment of the
mother with pembrolizumab (MK-3475), breastfeeding should be discontinued if the
mother is treated with pembrolizumab (MK-3475). These potential risks may also apply
to other agents used in this study. Men treated or enrolled on this protocol must also
agree to use adequate contraception prior to the study, for the duration of study
participation, and 180 days after completion of study treatment.
- Ability to understand and the willingness to sign a written informed consent document
(or have legally acceptable representative sign, if applicable).
- Patients who have recovered from adverse events due to prior anti-cancer therapy
(i.e., have residual toxicities > Grade 1) with the exception of alopecia.
- Note: If patients received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.
- Has not received transfusion of blood products (including platelets or red blood
cells) or administration of colony stimulating factors (including granulocyte
colony-stimulating factor [G-CSF], granulocyte macrophage colony-stimulating factor
[GM-CSF], or recombinant erythropoietin) within 4 weeks prior to Study Day 1.
Exclusion Criteria:
- 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 7 days of 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.
Note: Other protocol defined Inclusion/Exclusion criteria may apply.
Eligibility last updated 3/10/23. Questions regarding updates should be directed to the study team contact.