Study of ZEN003694 and Abemaciclib for Advanced Cancers
This study is testing two anti-cancer drugs, ZEN003694 and abemaciclib, for adults and adolescents (12-17 years old) with certain cancers that have spread or cannot be removed by surgery. These include NUT carcinoma, breast cancer, and other solid tumors. Researchers want to find the safest and most effective dose of these drugs when given together. ZEN003694 works by targeting a protein family called BET, which may help stop tumor growth. Abemaciclib may slow tumor growth by blocking enzymes needed for cancer cells to multiply. The goal is to see if this combination can shrink or stabilize cancer. The study plans to enroll 45 participants.
- Study design
- This is an interventional study that will first find the best dose of the drugs, then expand to test their effectiveness. It is not specified if participants will be randomly assigned to different groups.
- What's involved
- You would take ZEN003694 and abemaciclib by mouth daily in cycles of 28 days. You would also have imaging tests, blood draws, and tumor biopsies throughout the study.
- Compensation
- Not stated in the trial record.
- Follow-up
- The study will track your progress for up to 5 years to see how well the treatment works and to monitor for any side effects.
AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.
NCT05372640
Testing the Safety and Efficacy of the Combination of Two Anti-cancer Drugs, ZEN003694 and Abemaciclib, for Adult and Pediatric Patients (12-17 Years) With Metastatic or Unresectable NUT Carcinoma, Breast Cancer and Other Solid Tumors
Recruiting
PHASE1Ages 12+InterventionalTreatmentNational Cancer Institute (NCI)Government-funded
~45 participants
Updated 2026-07-31 on ClinicalTrials.gov
What's tested:AbemaciclibBET Bromodomain Inhibitor ZEN-3694Biopsy ProcedureBiospecimen CollectionDiagnostic Imaging Testing
At a glance
Recruiting sites
7 of 7 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Maximum tolerated dose or recommended phase 2 dose (Phase I dose escalation)
Measured over During the first cycle of therapy (28 days)
+7 more outcomes measured
Conditions
Where it's being run
7 sites across 4 statesCalifornia4
Massachusetts1
Pennsylvania1
Texas1
Study leadership
- Jia Luo · PRINCIPAL_INVESTIGATOR · Dana-Farber - Harvard Cancer Center LAO
Who to contact
Site Public Contact
Do you actually qualify for this trial?
Add a private profile and we'll compare every criterion below against your situation — and tell you which ones are met, uncertain, or excluding.
Eligibility criteria
Inclusion
Participants must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
Dose Escalation Cohort Only: Participants must have evaluable disease or measurable disease per RECIST 1.1 criteria
Dose Expansion Cohort Only:
Participants must have a diagnosis of NUT carcinoma (NC) based on standard criteria for the disease, with diagnostic testing performed in a Clinical Laboratory Improvement Act (CLIA) certified laboratory:
Ectopic expression of NUT protein per World Health Organization (WHO) criteria as determined by immunohistochemistry (IHC) testing, OR
Detection of the NUT gene translocation as determined by fluorescence in situ hybridization (FISH) testing, OR
Detection of the NUT gene translocation as determined by either deoxyribonucleic acid (DNA) next-generation sequencing (NGS) or ribonucleic acid (RNA) sequencing.
Participants must have measurable disease per RECIST 1.1 criteria
Any number of prior lines of therapy in the metastatic setting are allowed, including prior BET inhibitor therapy and prior CDK4/6 inhibitor therapy
Patients who received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events \[CTCAE\] grade =\< 1) from the acute effects of chemotherapy except for residual alopecia or grade 2 peripheral neuropathy
Patients who received radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. A washout period of at least 14 days is required between end of radiotherapy
Participants may have previously undergone surgical resection
Age \>= 12 years. Patients 12-17 years of age must be \> 40 kg at enrollment. Patients 12-17 years of age will not participate in the mandatory tumor biopsies. Since there is no data on patients less than 18 years of age, this population may require lower doses and additional safety precautions and should be closely monitored. Because no dosing or adverse event data are currently available on the use of ZEN003694 in combination with abemaciclib in patients \< 12 years of age, younger children are excluded from this study
Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 for participants \>= 16 years of age, Lansky \>= 50% if \< 16 years of age
Hemoglobin \>= 8 g/dL; Patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion
Absolute neutrophil count \>= 1.5 x 10\^9/L
Platelets \>= 1 x 10\^11/L
Total bilirubin =\< 1.5 x institutional upper limit of normal (ULN) for age. Patients with Gilbert's syndrome with a total bilirubin =\< 2.0 times ULN and direct bilirubin within normal limits are permitted
Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase \[SGOT\])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase \[SGPT\]) =\< 2.5 x institutional ULN for age
Serum or plasma creatinine =\< 1.5 x institutional ULN OR calculated creatinine clearance \>= 50 mL/min (via the chronic kidney disease epidemiology \[CKD-EPI\] glomerular filtration rate estimation) for participants \>= 18 years old, or 60 mL/min/1.73m\^2 for patients 12-17 years as calculated based on bedside Schwartz formula
Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
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. Hepatitis C (HepC antibody) testing is required. Hepatitis C RNA is optional; however, a confirmatory negative Hepatitis C RNA test must be obtained to be able to enroll participants with positive Hepatitis C antibody due to prior resolved disease
Patients with treated brain metastases are eligible if follow-up brain imaging after central nervous system (CNS)-directed therapy shows no evidence of progression and has been clinically stable for at least 1 month. Patients must meet the following criteria:
Disease outside the CNS is present
Recovery from acute toxicity associated with the treatment to =\< CTCAE grade 1 or baseline (with the exception of alopecia), with no requirement for escalating doses of corticosteroids over the past 7 days
Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
Patients should be New York Heart Association Functional Classification of class 2B or better
Ability to swallow and retain oral medications
The effects of ZEN00364 and abemaciclib on the developing human fetus are unknown. For this reason and because BETi and CDKi-inhibiting agents 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 and for the duration of study participation. Women of child-bearing potential must have a negative pregnancy test prior to study entry. 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. Men and women treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 weeks after completion of ZEN003694 and abemaciclib administration
For female subjects of child-bearing potentially receiving ZEN003694, hormonal means of birth control alone, such as oral, injectable, dermal, subdermal or topical contraceptives are NOT acceptable forms of birth control given that their efficacy has not been evaluated when given in combination with the investigational drugs. "Adequate contraception" is defined as the following:
Contraceptive methods with a failure rate of =\< 1% used in combination with the barrier method. The following contraceptive methods are acceptable to use in combination with the barrier method: intrauterine device (IUD), intrauterine system (IUS), or oral contraceptive pills (OCPs) that meet the \< 1% failure rate as stated in the product label. Note: Hormonal IUDs/OCPs may only be used if the following criteria are met: male condoms are required AND subjects are informed of the potential for reduced systemic hormone levels from the IUD/OCP when taking ZEN003694. Alternatively, male partner sterilization (vasectomy with documentation of azoospermia) prior to the female subject's entry into the study, and this male is the sole partner for that subject. For this definition, "documented" refers to the outcome of the investigator's/designee's medical examination of the subject or review of the subject's medical history for study eligibility, as obtained via a verbal interview with the subject or from the subject's medical records
Male subjects with female partners of child-bearing potential must use one of the following contraceptive methods:
Vasectomy with documentation of azoospermia OR
Condom use PLUS partner use of a highly effective contraceptive (=\< 1% rate of failure per year) such as intrauterine device or system, or hormonal birth control such as contraceptive subdermal implant, combined estrogen and progestogen oral contraceptive, injectable progestogen, contraceptive vaginal ring, or percutaneous contraceptive patches
Male subjects should not donate sperm while on study and for 12 weeks after the last dose of study medication. Male subjects whose partners are or become pregnant must continue to use condoms for 12 weeks after the last dose of study medication
Women of childbearing potential must have a negative pregnancy test within 7 days of starting treatment
Ability to understand and the willingness to sign a written informed consent document. Participants with impaired decision-making capacity who have a legally-authorized representative (LAR) and/or family member available may be eligible after discussion with the Principal Investigator of this study. There will be a separate assent process for minors
Exclusion
Participants who have had cytotoxic chemotherapy, immunotherapy, or other investigational therapy within 2 weeks prior to entering the study. There is a two-week required washout period for previous BET inhibitor therapy
Participants who have had radiotherapy within at least 2 weeks prior to entering the study. Stereotactic radiosurgery (SRS) within 1 week prior to entering the study will be allowed
Participants who have had major surgery within 3 weeks prior to entering the study
Participants who have received tyrosine kinase inhibitors (TKIs) or small molecules within 5 half-lives or 1 week (whichever is shorter) of study entry
Patients who are receiving any other investigational agents
History of allergic reactions attributed to compounds of similar chemical or biologic composition to ZEN003694 or abemaciclib
Patients requiring medications or substances that are strong inhibitors or strong inducers of CYP3A4 or CYP3A enzymes are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694 and abemaciclib. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated list such as http://medicine.iupui.edu/clinpharm/ddis/table.aspx; medical reference texts such as the Physicians' Desk Reference may also provide this information. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Patients with uncontrolled intercurrent illness, including but not limited to: ongoing or active infection requiring systemic therapy, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment (e.g. estimated creatinine clearance \< 30ml/min), history of major surgical resection involving the stomach or small bowel, or preexisting Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline grade 2 or higher diarrhea that, in the judgment of the investigator, would preclude participation in this study
Patients receiving any medications or substances that are strong inhibitors or inducers of CYP3A4 or substrates of CYP1A2 with narrow therapeutic windows are ineligible. Strong inhibitors or inducers of CYP3A4 must be discontinued at least 7 days prior to the first dose of ZEN003694. As proton pump inhibitors (PPIs), H2 receptor antagonists, and antacids may alter the pharmacokinetics of ZEN003694 by reducing ZEN003694 exposure, patients receiving proton pump inhibitors are ineligible. If H2 blockers or other acid reducing agents are used concomitantly with ZEN003694, a staggered dosing schedule should be used. Because the lists of these agents are constantly changing, it is important to regularly consult a frequently-updated medical reference. As part of the enrollment/informed consent procedures, the patient will be counseled on the risk of interactions with other agents, and what to do if new medications need to be prescribed or if the patient is considering a new over-the-counter medicine or herbal product
Pregnant women are excluded from this study because ZEN003694 is a BETi 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 ZEN003694, breastfeeding should be discontinued if the mother is treated with ZEN003694. These potential risks may also apply to other agents used in this study
Fridericia's formula-corrected QT interval (QTcF) \>= 450 msec on screening electrocardiogram (ECG) by Fredericia (machine or manual read allowed). Patients should avoid medications which prolong the QT
Patients receiving any medications or substances that are Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) or Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed
Patients with radiation to \> 25% of the bone marrow
Patients who have had a bone-targeted radionuclide within 6 weeks of the first dose of ZEN003694
Myocardial infarction or unstable angina within 6 months prior to the first dose of ZEN003694
Impairment of gastrointestinal function that may significantly alter the absorption of ZEN003694 and/or abemaciclib
The patient has a personal history of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest
What this trial measures
- Maximum tolerated dose or recommended phase 2 dose (Phase I dose escalation)During the first cycle of therapy (28 days)
The toxicity of the combination will be assessed using Common Terminology Criteria for Adverse Events (CTCAE) version (v). 5.0 criteria.
- Incidence of adverse events (Phase I dose expansion)Up to 5 years
Safety will be reported with descriptive statistics. Toxicity will be graded according to National Cancer Institute CTCAE, v5.0. Toxicities will be summarized by maximum grade and by treatment arm. Incidence rate of each toxicity will be reported with 95% exact confidence intervals.
- Overall response rate (Phase I dose expansion)Up to 5 years
Will be graded as complete response (CR), partial response (PR), stable disease (SD) and progressive disease.
- Clinical benefit rate (CBR) (Phase I dose expansion)Up to 5 years
Clinical benefit is defined as CR, PR or SD \>= 24 weeks according to Response Evaluation Criteria in Solid Tumors 1.1. CBR will be reported with 90% exact confidence intervals.
- Duration of response (DoR) (Phase I dose expansion)From the time measurement criteria are met for CR or PR (whichever is first recorded) until the first date that recurrent or progressive disease is objectively documented, assessed up to 5 years
Median DoR will be reported with ranges.
- Time to response (Phase I dose expansion)From the time initiation of therapy to the time measurement criteria are met for CR or PR (whichever is first recorded), assessed up to 5 years
- Overall survival (Phase I dose expansion)From study enrollment until death due to any cause, assessed up to 5 years
- Progression free survival (Phase I dose expansion)From study enrollment until the identification of disease progression or death, assessed up to 5 years