Recruiting
Phase 1
Phase 2

Iadademstat, Atezolizumab, Durvalumab

Sponsor:

National Cancer Institute (NCI)

Code:

NCT06287775

Conditions

Extensive Stage Lung Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Atezolizumab

Biopsy Procedure

Biospecimen Collection

Computed Tomography

Durvalumab

Study Details

Brief summary:

This phase I/II trial tests the safety, side effects, and best dose of iadademstat when given together with atezolizumab or durvalumab, and studies the effect of the combination in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage) who initially received standard of care chemotherapy and immunotherapy. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients with extensive stage small cell lung cancer.

Conditions

Extensive Stage Lung Small Cell Carcinoma

Stage IV Lung Cancer AJCC v8

Study ID

NCT06287775

Start date

Apr 8, 2025

Status verified date

Aug, 2026

Completion date

Jul 25, 2029

Anticipated

Primary completion date

Jul 25, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed small cell lung cancer (SCLC)
  • Patients who have been treated with platinum etoposide chemotherapy plus either atezolizumab or durvalumab immunotherapy for at least 4 cycles, and no more than 6 cycles, with either a radiographic response or stable disease. Patients are eligible if a maximum of 2 cycles of atezolizumab or durvalumab were omitted with initial treatment
  • Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with atezolizumab and durvalumab in patients <18 years of age, children are excluded from this study
  • Body weight ≥ 50 kg
  • Patient is able to swallow oral medications
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%). This assessment for eligibility will take place after patients have received 4 cycles of standard of care (SOC) chemotherapy-ICI
  • Leukocytes ≥ 2,000/mcL
  • Lymphocyte count ≥ 500/mcL
  • Absolute neutrophil count ≥ 1,500/mcL
  • Hemoglobin ≥ 9 g/dL
  • Platelets ≥ 100,000/mcL
  • Albumin ≥ 3 g/dL
  • Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN unless liver metastases are present, in which case it must be ≤ 5 × ULN
  • Glomerular filtration rate (GFR) ≥ 45 mL/min
  • 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
  • Patients with treated brain metastases (no escalating steroid use) or asymptomatic, untreated brain metastases (≤ 5 mm without significant edema) are eligible. Brain metastases must not be new after completion of chemotherapy
  • 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
  • Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Pregnant women are excluded from this study because atezolizumab and durvalumab are monoclonal antibody agents with the potential for teratogenic or abortifacient effects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  • Women < 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  • Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses >1 year ago, had chemotherapy-induced menopause with last menses > 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
  • The effects of iadademstat, atezolizumab, and durvalumab on the developing human fetus are unknown. For this reason and because monoclonal antibody agents are known to be teratogenic, women of child-bearing potential and males with females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to registration, for the duration of study participation, and for 150 days after the last dose of study medication. 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.

  • Females of childbearing potential must agree to:

  • Use effective contraception during the trial and 150 days after the end of treatment.
  • Practice true abstinence during the trial and 150 days after the end of treatment.
  • Have a negative urine pregnancy test at screening.
  • Not to donate or freeze egg(s) during the course of this study or within 150 days after receiving their last dose of study drug.
  • Male patients even if surgically sterilized (i.e., status post-vasectomy) must agree to:

  • Use effective contraception during the entire study treatment period and through 150 days after the last dose of study drug.
  • Not to donate or freeze sperm during the course of this study or within 150 days after receiving their last dose of study drug.
  • Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with atezolizumab and durvalumab, female participants who are breastfeeding must agree to discontinue breastfeeding. These potential risks may also apply to iadademstat
  • Ability to understand and the willingness to sign a written informed consent document. Legally authorized representatives may sign and give informed consent on behalf of study participants

Exclusion Criteria:

  • Patients who receive maintenance ICI therapy prior to cycle 1, day 1
  • Patients medicated with anti-depressants reported to have KDM1A/LSD1 inhibitory activity: Tranylcypromine or phenelzine
  • Patients who have not recovered from grade ≥2 adverse events (AEs) due to prior anti-cancer therapy with the exception of alopecia, vitiligo, and the laboratory values defined in the inclusion criteria.

  • Patients with grade ≥ 2 neuropathy will be evaluated on a case-by-case basis after consultation with the study physician
  • Patients who are receiving any other investigational agents or any other agent administered for the treatment of the patient's cancer within four half-lives or 4 weeks prior to registration, whichever is shorter
  • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon \[IFN\]-α or interleukin \[IL\]-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to cycle 1, day 1
  • Treatment with systemic immunosuppressive medications (including, but not limited to, prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor \[anti-TNF\] agents) within 2 weeks prior to registration or anticipation of need for systemic immunosuppressive medication during study treatment, with the following exceptions:

  • Patients who have received acute, low dose, systemic immunosuppressant medications or one-time pulse dose of systemic immunosuppressant medication (e.g., 48 hours of corticosteroids for a contrast allergy) are eligible after Principal Investigator confirmation has been obtained.
  • Patients who have received mineralocorticoids (e.g., fludrocortisone), corticosteroids for chronic obstructive pulmonary disease (COPD) or asthma, or low-dose corticosteroids for orthostatic hypotension or adrenocortical insufficiency are eligible
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to iadademstat, atezolizumab, or durvalumab. In particular, a history of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric antibodies, fusion proteins, or Chinese hamster ovary cell products or to any component of the atezolizumab formulation
  • Atezolizumab Concomitant Medication Considerations: Patients are not allowed to receive immunostimulatory agents, immunosuppressive medications, or herbal and natural remedies
  • Durvalumab Concomitant Medication Considerations: Patients are not allowed to receive immunosuppressive medications, EGFR TKIs, or herbal and natural remedies
  • Iadademstat Concomitant Medication Considerations: Patients are not allowed to receive prophylactic hematopoietic colony stimulating factors, any complementary or alternative medicine \[any of various systems of healing or treating disease (as non-prescription drugs, herbal medicine and homeopathy)\]. Use of these types of treatments must be terminated 1 week prior to registration
  • History of allogenic organ transplantation
  • Patients with active tuberculosis (TB)
  • Patients with uncontrolled intercurrent illness or any other significant condition(s) that would make participation in this protocol unreasonably hazardous
  • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted
  • Unstable angina, symptomatic or otherwise uncontrolled arrhythmia (does not include stable, lone atrial fibrillation), Fridericia's correction (QTcF) > 480 ms based on screening electrocardiogram (ECG), myocardial infarction ≤ 3 months prior to registration, cerebrovascular accidents ≤ 3 months before registration. Patient has congestive heart failure New York Heart Association (NYHA) class 2, 3 or 4 or patients with a history of congestive heart failure NYHA class 2, 3 or 4 in the past, unless a screening echocardiogram performed within 1 month prior to registration demonstrates a left ventricular ejection fraction that is ≥ 45%
  • History or risk of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

  • Patients with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus (HbA1c < 8%) on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:

  • Rash must cover less than 10% of body surface area (BSA).
  • Disease is well controlled at baseline and only requiring low potency topical steroids.
  • No acute exacerbations of underlying condition within the last 12 months (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) within the previous 12 months.
  • Any chronic skin condition that does not require systemic therapy.
  • Patients without active disease in the last 5 years may be included but only after consultation with the study physician.
  • Patients with celiac disease controlled by diet alone
  • Patients should not receive vaccines 30 days prior to registration. Patient is informed to not receive vaccines during treatment and through 30 days after the last dose of study treatment with the exception of seasonal influenza vaccines and vaccines intended to prevent SARS-CoV-2, pneumococcal infection and coronavirus disease 2019 (COVID-19). If a patient had received a live attenuated vaccine within 30 days of the first dose of trial treatment, eligibility should be discussed with the investigator
  • Patient has had major surgery within 4 weeks prior to registration
  • Patient has radiation therapy within 4 weeks prior to registration, excluding palliative and central nervous system (CNS) radiation
  • Manifestations of malabsorption due to prior gastrointestinal (GI) surgery, GI disease, or for an unknown reason that may alter the absorption of iadademstat. In addition, patients with enteric stomata are also excluded
  • Patients with history of clinically significant bleeding, specifically any history of intracranial hemorrhage / hemorrhagic cardiovascular accident (CVA), or patients with gastrointestinal bleeding within the 3 months prior to registration
  • Patients with known irreversible bleeding disorders or receiving antiplatelet therapy for other indications
  • Patients with uncontrolled disseminated intravascular coagulation
  • Patients who refuse or are unable to potentially receive blood products

Study Design

Enrollment

45 participants

Anticipated

Allocation

Randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase I (iadademstat, atezolizumab, durvalumab)

Patients in Phase I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

active comparator: Phase II Arm II (atezolizumab, durvalumab)

Patients in Phase II Arm II continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

experimental: Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Patients in Phase II Arm I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Interventions

Atezolizumab

Given IV

Biopsy Procedure

Undergo optional tumor biopsy

Biospecimen Collection

Undergo blood and urine sample collection

Computed Tomography

Undergo CT scan

Durvalumab

Given IV

Echocardiography Test

Undergo ECHO

Iadademstat

Given PO

Magnetic Resonance Imaging

Undergo MRI

Multigated Acquisition Scan

Undergo MUGA

Primary outcome measure

  • Progression free survival [ Time Frame: From start of treatment to time of progression or death, whichever occurs first, up to 2 years ]

Central Contacts and Locations

Locations

City of Hope Comprehensive Cancer Center

Recruiting

Duarte, California, United States, 91010

Contacts

Site Public Contact

800-826-4673becomingapatient@coh.org

Principal Investigator:

Matthew Lee

City of Hope at Irvine Lennar

Recruiting

Irvine, California, United States, 92618

Contacts

Site Public Contact

877-467-3411

Principal Investigator:

Matthew Lee

UC San Diego Moores Cancer Center

Recruiting

La Jolla, California, United States, 92093

Contacts

Site Public Contact

858-822-5354cancercto@ucsd.edu

Principal Investigator:

Lyudmila A. Bazhenova

University of California Davis Comprehensive Cancer Center

Recruiting

Sacramento, California, United States, 95817

Contacts

Site Public Contact

916-734-3089

Principal Investigator:

Surbhi Singhal

Yale University

Recruiting

New Haven, Connecticut, United States, 06520

Contacts

Site Public Contact

203-785-5702canceranswers@yale.edu

Principal Investigator:

Anne C. Chiang

Yale-New Haven Hospital North Haven Medical Center

Recruiting

North Haven, Connecticut, United States, 06473

Contacts

Site Public Contact

203-785-5702canceranswers@yale.edu

Principal Investigator:

Anne C. Chiang

Smilow Cancer Hospital Care Center-Trumbull

Recruiting

Trumbull, Connecticut, United States, 06611

Contacts

Site Public Contact

203-785-5702canceranswers@yale.edu

Principal Investigator:

Anne C. Chiang

MedStar Georgetown University Hospital

Recruiting

Washington D.C., District of Columbia, United States, 20007

Contacts

Site Public Contact

202-444-2223

Principal Investigator:

Stephen V. Liu

UF Health Cancer Institute - Gainesville

Recruiting

Gainesville, Florida, United States, 32610

Contacts

Site Public Contact

352-273-8010

Principal Investigator:

Aline F. Fares

Emory University Hospital Midtown

Recruiting

Atlanta, Georgia, United States, 30308

Contacts

Site Public Contact

888-946-7447

Principal Investigator:

Ticiana A. Leal

Emory University Hospital/Winship Cancer Institute

Recruiting

Atlanta, Georgia, United States, 30322

Contacts

Site Public Contact

404-778-1868

Principal Investigator:

Ticiana A. Leal

Emory Saint Joseph's Hospital

Recruiting

Atlanta, Georgia, United States, 30342

Contacts

Site Public Contact

404-851-7115

Principal Investigator:

Ticiana A. Leal

University of Chicago Comprehensive Cancer Center

Recruiting

Chicago, Illinois, United States, 60637

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

UC Comprehensive Cancer Center at Silver Cross

Recruiting

New Lenox, Illinois, United States, 60451

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

University of Chicago Medicine-Orland Park

Recruiting

Orland Park, Illinois, United States, 60462

Contacts

Site Public Contact

773-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

UChicago Medicine Northwest Indiana

Recruiting

Crown Point, Indiana, United States, 46307

Contacts

Site Public Contact

855-702-8222cancerclinicaltrials@bsd.uchicago.edu

Principal Investigator:

Noura Choudhury

University of Kansas Clinical Research Center

Recruiting

Fairway, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Chao H. Huang

University of Kansas Cancer Center

Recruiting

Kansas City, Kansas, United States, 66160

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Chao H. Huang

University of Kansas Hospital-Indian Creek Campus

Recruiting

Overland Park, Kansas, United States, 66211

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Chao H. Huang

University of Kansas Hospital-Westwood Cancer Center

Recruiting

Westwood, Kansas, United States, 66205

Contacts

Site Public Contact

913-588-3671KUCC_Navigation@kumc.edu

Principal Investigator:

Chao H. Huang

University of Kentucky/Markey Cancer Center

Recruiting

Lexington, Kentucky, United States, 40536

Contacts

Site Public Contact

859-257-3379

Principal Investigator:

Zhonglin Hao

University of Maryland/Greenebaum Cancer Center

Recruiting

Baltimore, Maryland, United States, 21201

Contacts

Site Public Contact

800-888-8823

Principal Investigator:

Samuel Rosner

Johns Hopkins University/Sidney Kimmel Cancer Center

Recruiting

Baltimore, Maryland, United States, 21287

Contacts

Site Public Contact

410-955-8804jhcccro@jhmi.edu

Principal Investigator:

Christine L. Hann

Memorial Sloan Kettering Cancer Center

Recruiting

New York, New York, United States, 10065

Contacts

Site Public Contact

212-639-7592

Principal Investigator:

Charles M. Rudin

Carolinas Medical Center/Levine Cancer Institute

Recruiting

Charlotte, North Carolina, United States, 28203

Contacts

Site Public Contact

800-804-9376

Principal Investigator:

Christopher R. Pallas

Atrium Health Cabarrus/LCI-Concord

Recruiting

Concord, North Carolina, United States, 28025

Contacts

Site Public Contact

800-804-9376

Principal Investigator:

Christopher R. Pallas

Wake Forest University Health Sciences

Recruiting

Winston-Salem, North Carolina, United States, 27157

Contacts

Site Public Contact

336-713-6771

Principal Investigator:

Jimmy Ruiz

University of Cincinnati Cancer Center-UC Medical Center

Recruiting

Cincinnati, Ohio, United States, 45219

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Jennifer Leddon

Case Western Reserve University

Recruiting

Cleveland, Ohio, United States, 44106

Contacts

Site Public Contact

800-641-2422CTUReferral@UHhospitals.org

Principal Investigator:

Afshin Dowlati

Ohio State University Comprehensive Cancer Center

Recruiting

Columbus, Ohio, United States, 43210

Contacts

Site Public Contact

800-293-5066Jamesline@osumc.edu

Principal Investigator:

Asrar AlAhmadi

University of Cincinnati Cancer Center-West Chester

Recruiting

West Chester, Ohio, United States, 45069

Contacts

Site Public Contact

513-584-7698cancer@uchealth.com

Principal Investigator:

Jennifer Leddon

UPMC Hillman Cancer Center

Recruiting

Pittsburgh, Pennsylvania, United States, 15232

Contacts

Site Public Contact

412-647-8073

Principal Investigator:

Liza C. Villaruz

University of Virginia Cancer Center

Recruiting

Charlottesville, Virginia, United States, 22908

Contacts

Site Public Contact

434-243-6303uvacancertrials@hscmail.mcc.virginia.edu

Principal Investigator:

Ryan D. Gentzler

VCU Massey Comprehensive Cancer Center

Recruiting

Richmond, Virginia, United States, 23298

Contacts

Site Public Contact

804-628-6430CTOclinops@vcu.edu

Principal Investigator:

Jonathan D. Berkman

More Information

Sponsor

National Cancer Institute (NCI)

Last update posted

Sep 17, 2026

Last verified

Aug, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-09. This information was provided to ClinicalTrials.gov by National Cancer Institute (NCI) on 2026-09-17. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.