A Study of ZEN003694 in People With Squamous Cell Lung Cancer

NCT05607108 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 22-286
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Squamous Cell Lung Cancer

Keywords

Metastatic; Recurrent; ZEN003694; NSD3 Amplification; 22-286

Outcome Measures

Primary Outcomes (1)

• overall response rate (ORR)

  Response to ZEN003694 will be determined using the sum unidimensional measurements of the target lesions present on the scan. Unidimensional measurement rules will adhere to RECIST 1.1 guidelines.(6) Classification of response will be categorized by RECIST 1.1 (CR, PR, SD, PD).

  2 years

Study Arms (1)

ZEN003694

EXPERIMENTAL

All patients enrolled on the study will undergo treatment with ZEN003694 60mg po qd on a 5 days on/2 days off schedule in an every 21-day cycle. All assessments, including drug dosing, have a window of +/- 7 days unless otherwise noted.

Drug: ZEN003694

Interventions

ZEN003694 DRUG

ZEN003694 60mg po qd on a 5 days on 2 days off schedule in an every 21-day cycle

ZEN003694

Eligibility Criteria

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

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Memorial Sloan Kettering Cancer Center: lead
• Zenith Epigenetics: collaborator

Study Sites (7)

Memorial Sloan Kettering at Basking Ridge Limited Protocol Activities

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth (All Protocol Activities)

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen (All Protocol Activities)

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Suffolk-Commack (All Protocol Activities )

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester (All Protocol Activities)

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center (All Protocol Activities)

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau (All Protocol Activities)

Uniondale, New York, 11553, United States

RECRUITING

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Neoplasm Metastasis; Recurrence

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Disease Attributes

Study Officials

• Paul Paik, MD

  Memorial Sloan Kettering Cancer Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Paul Paik, MD

CONTACT

646-608-3759; paikp@mskcc.org

Mark Kris, MD

CONTACT

646-608-3914

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a single-arm phase 2 study of ZEN003694 in patients with advanced NSD3- amplified squamous cell lung cancer.

Study Record Dates

• First Submitted: November 1, 2022
• First Posted: November 7, 2022
• Study Start: November 1, 2022
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: March 11, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will share

Locations

US (7)