A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer

Status: Recruiting
Location: See all (42) locations...
Intervention Type: Procedure, Biological, Drug
Study Type: Interventional
Study Phase: Phase 1/Phase 2
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.

Eligibility
Participation Requirements
Sex: All
Minimum Age: 18
Healthy Volunteers: f
View:

• 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) 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

Locations
United States
California
City of Hope Comprehensive Cancer Center
RECRUITING
Duarte
City of Hope at Irvine Lennar
RECRUITING
Irvine
UC San Diego Moores Cancer Center
RECRUITING
La Jolla
University of California Davis Comprehensive Cancer Center
RECRUITING
Sacramento
Connecticut
Smilow Cancer Hospital Care Center at Saint Francis
RECRUITING
Hartford
Yale University
RECRUITING
New Haven
Yale-New Haven Hospital North Haven Medical Center
RECRUITING
North Haven
Smilow Cancer Hospital Care Center at Long Ridge
RECRUITING
Stamford
Smilow Cancer Hospital Care Center-Trumbull
RECRUITING
Trumbull
Washington, D.c.
MedStar Georgetown University Hospital
RECRUITING
Washington D.c.
Florida
University of Florida Health Science Center - Gainesville
RECRUITING
Gainesville
Moffitt Cancer Center
RECRUITING
Tampa
Georgia
Emory Saint Joseph's Hospital
RECRUITING
Atlanta
Emory University Hospital Midtown
RECRUITING
Atlanta
Emory University Hospital/Winship Cancer Institute
RECRUITING
Atlanta
Illinois
University of Chicago Comprehensive Cancer Center
RECRUITING
Chicago
UC Comprehensive Cancer Center at Silver Cross
RECRUITING
New Lenox
University of Chicago Medicine-Orland Park
RECRUITING
Orland Park
Indiana
UChicago Medicine Northwest Indiana
RECRUITING
Crown Point
Kansas
University of Kansas Clinical Research Center
RECRUITING
Fairway
University of Kansas Cancer Center
RECRUITING
Kansas City
University of Kansas Hospital-Indian Creek Campus
RECRUITING
Overland Park
University of Kansas Hospital-Westwood Cancer Center
RECRUITING
Westwood
Kentucky
University of Kentucky/Markey Cancer Center
RECRUITING
Lexington
Maryland
Johns Hopkins University/Sidney Kimmel Cancer Center
RECRUITING
Baltimore
University of Maryland/Greenebaum Cancer Center
RECRUITING
Baltimore
North Carolina
Carolinas Medical Center/Levine Cancer Institute
RECRUITING
Charlotte
Atrium Health Cabarrus/LCI-Concord
RECRUITING
Concord
Wake Forest University Health Sciences
RECRUITING
Winston-salem
New Jersey
Memorial Sloan Kettering Basking Ridge
RECRUITING
Basking Ridge
Memorial Sloan Kettering Monmouth
RECRUITING
Middletown
Memorial Sloan Kettering Bergen
RECRUITING
Montvale
New York
Memorial Sloan Kettering Commack
RECRUITING
Commack
Memorial Sloan Kettering Westchester
RECRUITING
Harrison
Memorial Sloan Kettering Cancer Center
RECRUITING
New York
Memorial Sloan Kettering Nassau
RECRUITING
Uniondale
Ohio
University of Cincinnati Cancer Center-UC Medical Center
RECRUITING
Cincinnati
Case Western Reserve University
RECRUITING
Cleveland
Ohio State University Comprehensive Cancer Center
RECRUITING
Columbus
University of Cincinnati Cancer Center-West Chester
RECRUITING
West Chester
Pennsylvania
University of Pittsburgh Cancer Institute (UPCI)
RECRUITING
Pittsburgh
Virginia
University of Virginia Cancer Center
RECRUITING
Charlottesville
Time Frame
Start Date: 2025-04-08
Estimated Completion Date: 2029-07-25
Participants
Target number of participants: 45
Treatments
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.
Sponsors
Leads: National Cancer Institute (NCI)

This content was sourced from clinicaltrials.gov

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