A Study of ZEN003694 in People With Squamous Cell Lung Cancer
Phase 2 Trial of ZEN003694 in Squamous Cell Lung Cancer Patients Harboring NSD3 Amplification
Who can join
As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.
- Age
- 18 Years and older
- Sex
- All sexes
- Healthy volunteers
- Not accepted
- Compensation
- Not stated
Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.
What to expect
No one can promise a trial will help you personally — that is what the research is trying to find out.
What participation involves
Not stated in the study description — ask the study team about visits and procedures.
- Compensation
- Not stated
- Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
- Participants are monitored closely by the research team throughout the study.
- Some participants may receive access to an investigational treatment, which is still being studied.
- Your participation helps researchers learn whether this approach could help future patients.
About this study
In plain language
This study tests whether ZEN003694 helps adults with advanced squamous cell lung cancer and extra copies of the NSD3 gene. The drug blocks proteins that may help the cancer grow.
The purpose of this study is to find out whether ZEN003694 is an effective treatment for people with advanced squamous cell lung cancer with a mutation in the NSD3 gene. ZEN003694 is a type of drug called a BET inhibitor. Researchers think ZEN003694 may help here because the drug works by blocking a group of proteins called bromodomain and extra-terminal (BET) proteins, which may counteract the effect of NSD3 on tumor growth. Blocking these proteins may slow or stop the growth of the cancer.
Compensation is read from the study's own description and may be missing — always confirm with the study team.
Eligibility
Who can join
- Be age 18 or older with squamous cell lung cancer confirmed by a tissue test. The cancer must have come back or spread.
- Have a gene test showing extra copies of NSD3.
- Have already received platinum-based chemotherapy and immunotherapy, together or one after the other.
- Be able to care for yourself and be up and about for at least half of your waking hours.
- Meet the study’s blood cell, liver, kidney, and blood-clotting test limits, and be able to swallow capsules.
- Cancer that has spread to the brain may be allowed if it causes no symptoms and was treated before or is no larger than 1 cm. It must need no more than 10 mg of prednisone or a similar steroid daily.
- If taking steroids, use no more than 10 mg of prednisone or a similar dose daily. The dose must be stable for at least 2 weeks before treatment and stay stable during treatment.
- Follow the study’s birth control and egg or sperm donation rules. Women who could become pregnant need pregnancy tests. No breastfeeding is allowed during treatment or for 7 months after the last dose.
Who can't join
- Past treatment with an experimental BET inhibitor.
- Recent cancer drug treatment: within 2 weeks or the time for five half-lives, whichever is shorter. A half-life is the time for half a drug to leave the body. Radiation within 2 weeks also excludes you.
- Use of certain medicines that affect how the body handles drugs. Some must be stopped at least 7 days before treatment.
- Certain heart problems, including weak pumping, abnormal heart rhythms, or uncontrolled heart failure; or a heart attack or unstable chest pain within 6 months.
- Serious health problems that could make joining unsafe, such as uncontrolled lung disease, active brain or spinal cord disease, or an uncontrolled infection needing treatment.
- Another active cancer needing treatment, or a known positive history of HIV, hepatitis B, or hepatitis C as defined by the study.
- Major surgery within 4 weeks, except surgery to diagnose a condition, dental surgery, or stent placement.
- Problems with blood clotting or platelets, the cells that help stop bleeding, or use of certain blood thinners. Some blood thinners are allowed under study rules.
Simplified for readability. The official criteria below are what the study team uses.
Official eligibility criteria
Inclusion Criteria: * Histologically-confirmed squamous cell lung cancer * Recurrent or metastatic disease * Patients with previously treated asymptomatic brain metastases requiring no more than 10mg prednisone (or equivalent) are allowed. Patients with asymptomatic brain metastases ≤ 1cm not requiring more than 10mg prednisone (or equivalent) are allowed. * Received prior first-line therapy: platinum-based chemotherapy and immunotherapy, given either concurrently or sequentially * Eastern Cooperative Oncology Group (ECOG) PS 0-2 * Evidence of NSD3 gain or amplification by NGS, including but not limited to evidence of 8p11 gain or amplification as determined by MSK IMPACT or MSK ACCESS, or a commercially available molecular assay that is FDA authorized. Note: ctDNA testing, including but not limited to MSK ACCESS and Guardant and Foundation * Adequate laboratory parameters at Screening including: * Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L * Platelet count ≥ 100,000/mm\^3 * Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) ≤ 2.0 ULN (≤ 5 x ULN if liver metastases are present) * Total bilirubin ≤ 1.25 x ULN * Calculated or measured eGFR ≥ 40 ml/min or serum creatinine ≤ 1.5 x ULN * Prothrombin time (PT), international normalized ratio (INR) and partial thromboplastin time (PTT) \< 1.5 x ULN * Ability to swallow capsules * Use of corticosteroids is allowed up to a daily dose of 10 mg prednisone or equivalent provided that the dose has been stable for at least 2 weeks prior to the start of ZEN003694 dosing and will remain stable during ZEN003694 treatment. * Females or males age ≥ 18 years (at time of signing informed consent) * Female subjects may be enrolled if they are not of childbearing potential, permanently sterile or who are post-menopausal defined as no menses for at least 1 year without an alternative medical cause and FSH levels in the post-menopausal range. Female subjects of childbearing potential may be enrolled if they consistently and correctly use a highly effective form of contraception. Highly effective forms of contraception include: combined (estrogen and progestogen hormonal contraceptives (oral, intravaginal, transdermal) associated with inhibition of ovulation; progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation; intrauterine device (IUD); intrauterine hormone-releasing system (IUS); bilateral tubal occlusion; vasectomized partner; sexual abstinence. Female subjects should not donate eggs from the time point of study drug administration until at least 7 months thereafter. * Males with partners of childbearing potential may be enrolled if they use a condom when having sex with a pregnant woman or with a non-pregnant female of childbearing potential from 21 days before the first dose of study drug through 4 months after the last dose of study drug, and males should not donate sperm from the time point of study drug administration until at least 4 months thereafter. Contraception should be considered for a non-pregnant female partner of childbearing potential * Females of childbearing potential must have a negative serum or urine pregnancy test before the first dose of study drugs and must agree to pregnancy tests during the study. * Females may not be breast-feeding at the first dose of study drugs, during study participation or through 7 months after the last dose of study drugs Exclusion Criteria: * Have previously received an investigational BET inhibitor * Have received prior systemic anti-cancer therapy or investigational therapy within 2 weeks or five half-lives, whichever is shorter, prior to the first dose of study drug * Radiation therapy within 2 weeks of first dose of study drug * Currently receiving medications known to be strong inducers or inhibitors of CYP3A4 and substrates of CYP1A2 with a narrow therapeutic window. Strong inducers and inhibitors of CYP3A4 and CYP1A2 substrates with narrow therapeutic ranges must be discontinued at least 7 days prior to the first administration of study drug. * Left ventricular ejection fraction less than the lower of 50% or the lower limit of institution's normal range * QTcF interval \> 470 msec * Known impaired cardiac function or clinically significant cardiac disease such as uncontrolled supraventricular arrhythmia, ventricular arrhythmia requiring therapy, or uncontrolled congestive heart failure (New York Heart Association functional class III or IV) * Myocardial infarction or unstable angina within 6 months prior to the first administration of study drug * Other clinically significant co-morbidities, such as uncontrolled pulmonary disease, active CNS disease, active, uncontrolled bacterial, viral, or fungal infection(s) requiring systemic therapy, or any other condition that could compromise safety or the patient's participation in the study * Other known active cancer requiring therapy at time of study entry * Historically positive (screening tests not required) for human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV) or with active infections. HBV positivity defined by positive hepatitis B surface antigen (HBsAg). HCV positivity defined as positive HCV viral load. * Major surgery other than diagnostic surgery, dental surgery or stenting within 4 weeks prior to the first administration of study drug * History of congenital or other deficiency in platelet function, or any known inherent or acquired coagulopathy, including current anticoagulation therapy (except for low-dose warfarin for port patency) * Current or anticipated use within 7 days prior to the first administration of study drug, or during the study, of strong P-gp inhibitors. * Use of oral Factor Xa inhibitors (i.e., rivaroxaban, apixaban, betrixaban, edoxaban otamixaban, letaxaban, eribaxaban) and Factor IIa inhibitors (i.e., dabigatran). Low molecular weight heparin is allowed. Note: except for subjects on anticoagulant therapy who must have PT-INR within therapeutic range as deemed appropriate by the Investigator.
Study sites (7)
NJ
- Memorial Sloan Kettering at Basking Ridge Limited Protocol Activities · Basking Ridge, NJ 07920Paul Paik, MD · Study contact · 646-608-3759More trials in Basking Ridge
- Memorial Sloan Kettering Monmouth (All Protocol Activities) · Middletown, NJ 07748Paul Paik, MD · Study contact · 646-608-3759More trials in Middletown
- Memorial Sloan Kettering Bergen (All Protocol Activities) · Montvale, NJ 07645Paul Paik, MD · Study contact · 646-608-3759More trials in Montvale
NY
- Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities ) · Commack, NY 11725Paul Paik, MD · Study contact · 646-608-3759More trials in Commack
- Memorial Sloan Kettering Westchester (All Protocol Activities) · East White Plains, NY 10604Paul Paik, MD · Study contact · 646-608-3759More trials in East White Plains
- Memorial Sloan Kettering Cancer Center (All Protocol Activities) · New York, NY 10065Paul Paik, MD · Study contact · 646-608-3759More trials in New York
- Memorial Sloan Kettering Nassau (All Protocol Activities) · Uniondale, NY 11553Paul Paik, MD · Study contact · 646-608-3759More trials in Uniondale