Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer

NCT06287775 | Recruiting Phase 1 FDA Drug

• 3 other identifiers: NCI-2024-0139810629UM1CA186691
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 43

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

Stage IV Lung Cancer AJCC v8; Extensive Stage Lung Small Cell Carcinoma

Outcome Measures

Primary Outcomes (1)

• Progression free survival

  Will be estimated using the method of Kaplan and Meier and will be presented with 95% confidence intervals as measure of effect size.

  From start of treatment to time of progression or death, whichever occurs first, up to 2 years

Secondary Outcomes (3)

• Objective response rate

  Up to 2 years

• Overall survival

  Up to 2 years

• Incidence of adverse events

  Up to 30 days after last dose of study treatment

Other Outcomes (4)

• Detection of circulating tumor deoxyribonucleic acid minimal residual disease

  Up to 2 years

• Impact of iadademstat on the correlation of immune checkpoint inhibitors (ICIs) and the presence of cachexia

  Up to 2 years

• Exposure response relationships of iadademstat in combination with ICIs

  Up to 2 years

Study Arms (3)

Phase I (iadademstat, atezolizumab, durvalumab)

EXPERIMENTAL

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.

Biological: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Echocardiography Test; Drug: Iadademstat; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan

Phase II Arm II (atezolizumab, durvalumab)

ACTIVE COMPARATOR

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.

Biological: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Echocardiography Test; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan

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

EXPERIMENTAL

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.

Biological: Atezolizumab; Procedure: Biopsy Procedure; Procedure: Biospecimen Collection; Procedure: Computed Tomography; Biological: Durvalumab; Procedure: Echocardiography Test; Drug: Iadademstat; Procedure: Magnetic Resonance Imaging; Procedure: Multigated Acquisition Scan

Interventions

Biospecimen Collection PROCEDURE

Undergo blood and urine sample collection

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Durvalumab BIOLOGICAL

Given IV

Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Iadademstat DRUG

Given PO

Also known as: ORY 1001, ORY-1001, RG 6016, RG6016, RO 7051790, RO7051790, trans-N1-((1R,2S)-2-Phenylcyclopropyl)-1,4-cyclohexanediamine

Phase I (iadademstat, atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Computed Tomography PROCEDURE

Undergo CT scan

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Echocardiography Test PROCEDURE

Undergo ECHO

Also known as: EC, Echocardiography

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Multigated Acquisition Scan PROCEDURE

Undergo MUGA

Also known as: Blood Pool Scan, Equilibrium Radionuclide Angiography, Gated Blood Pool Imaging, Gated Heart Pool Scan, MUGA, MUGA Scan, Multi-Gated Acquisition Scan, Radionuclide Ventriculogram Scan, Radionuclide Ventriculography, RNV Scan, RNVG, SYMA Scanning, Synchronized Multigated Acquisition Scanning

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Atezolizumab BIOLOGICAL

Given IV

Also known as: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG 7446, RG-7446, RG7446, RO 5541267, RO-5541267, RO5541267, Tecentriq

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Biopsy Procedure PROCEDURE

Undergo optional tumor biopsy

Also known as: Biopsy, BIOPSY_TYPE, Bx

Phase I (iadademstat, atezolizumab, durvalumab); Phase II Arm II (atezolizumab, durvalumab); Phase II, Arm I (iadademstat, atezolizumab, durvalumab)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (43)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

RECRUITING

City of Hope at Irvine Lennar

Irvine, California, 92618, United States

RECRUITING

UC San Diego Moores Cancer Center

La Jolla, California, 92093, United States

RECRUITING

University of California Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Smilow Cancer Hospital Care Center at Saint Francis

Hartford, Connecticut, 06105, United States

SUSPENDED

Yale University

New Haven, Connecticut, 06520, United States

RECRUITING

Yale-New Haven Hospital North Haven Medical Center

North Haven, Connecticut, 06473, United States

RECRUITING

Smilow Cancer Hospital Care Center at Long Ridge

Stamford, Connecticut, 06902, United States

RECRUITING

Smilow Cancer Hospital Care Center-Trumbull

Trumbull, Connecticut, 06611, United States

RECRUITING

MedStar Georgetown University Hospital

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

RECRUITING

UF Health Cancer Institute - Gainesville

Gainesville, Florida, 32610, United States

RECRUITING

Moffitt Cancer Center

Tampa, Florida, 33612, United States

SUSPENDED

Emory University Hospital Midtown

Atlanta, Georgia, 30308, United States

RECRUITING

Emory University Hospital/Winship Cancer Institute

Atlanta, Georgia, 30322, United States

RECRUITING

Emory Saint Joseph's Hospital

Atlanta, Georgia, 30342, United States

RECRUITING

University of Chicago Comprehensive Cancer Center

Chicago, Illinois, 60637, United States

RECRUITING

UC Comprehensive Cancer Center at Silver Cross

New Lenox, Illinois, 60451, United States

RECRUITING

University of Chicago Medicine-Orland Park

Orland Park, Illinois, 60462, United States

RECRUITING

UChicago Medicine Northwest Indiana

Crown Point, Indiana, 46307, United States

RECRUITING

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

RECRUITING

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

RECRUITING

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

RECRUITING

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

RECRUITING

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

RECRUITING

University of Maryland/Greenebaum Cancer Center

Baltimore, Maryland, 21201, United States

RECRUITING

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

RECRUITING

Memorial Sloan Kettering Basking Ridge

Basking Ridge, New Jersey, 07920, United States

RECRUITING

Memorial Sloan Kettering Monmouth

Middletown, New Jersey, 07748, United States

RECRUITING

Memorial Sloan Kettering Bergen

Montvale, New Jersey, 07645, United States

RECRUITING

Memorial Sloan Kettering Commack

Commack, New York, 11725, United States

RECRUITING

Memorial Sloan Kettering Westchester

Harrison, New York, 10604, United States

RECRUITING

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

RECRUITING

Memorial Sloan Kettering Nassau

Uniondale, New York, 11553, United States

RECRUITING

Carolinas Medical Center/Levine Cancer Institute

Charlotte, North Carolina, 28203, United States

RECRUITING

Atrium Health Cabarrus/LCI-Concord

Concord, North Carolina, 28025, United States

RECRUITING

Wake Forest University Health Sciences

Winston-Salem, North Carolina, 27157, United States

RECRUITING

University of Cincinnati Cancer Center-UC Medical Center

Cincinnati, Ohio, 45219, United States

SUSPENDED

Case Western Reserve University

Cleveland, Ohio, 44106, United States

RECRUITING

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

RECRUITING

University of Cincinnati Cancer Center-West Chester

West Chester, Ohio, 45069, United States

SUSPENDED

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

RECRUITING

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

RECRUITING

MeSH Terms

Conditions

Lung Neoplasms

Interventions

atezolizumab; Biopsy; Specimen Handling; durvalumab; Immunoglobulin G; Disulfides; iadademstat; Magnetic Resonance Spectroscopy

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Diagnostic Techniques, Surgical; Surgical Procedures, Operative; Investigative Techniques; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals; Spectrum Analysis; Chemistry Techniques, Analytical

Study Officials

• Charles M Rudin

  JHU Sidney Kimmel Comprehensive Cancer Center LAO

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 29, 2024
• First Posted: March 1, 2024
• Study Start: April 8, 2025
• Primary Completion (Estimated): July 25, 2029
• Study Completion (Estimated): July 25, 2029
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

US (43)