| Eligibility |
Inclusion Criteria:
- Patients must have histologically or cytologically confirmed small cell lung cancer
(SCLC)
- Patients must have measurable disease, defined as at least one lesion that can be
accurately measured in at least one dimension (longest diameter to be recorded for
non-nodal lesions) as = 20 mm (= 2 cm) by chest x-ray or as = 10 mm (= 1 cm) with CT
scan, MRI, or calipers by clinical exam or the shortest axis for nodal lesions as = 15
mm (= 1.5 cm) with CT scan
- Patients who have been treated with platinum etoposide chemotherapy plus either
atezolizumab or durvalumab immunotherapy for 4 cycles with either a radiographic
response or stable disease
- 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) = 60 mL/min/1.73 m^2 using Chronic Kidney Disease
Epidemiology Collaboration (CKD-epi) equation
- 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 are eligible if follow-up brain imaging after
central nervous system (CNS)-directed therapy shows no evidence of progression
- 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 study entry, 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 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 cycle 1, day 1, whichever is shorter
- Treatment with systemic immunostimulatory agents (including, but not limited to,
interferon [IFN]-a 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 cycle 1, day 1 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 start of study treatment
- 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 first
study treatment, cerebrovascular accidents = 3 months before study treatment start.
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 study entry
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 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 the first study dose
- Patient has radiation therapy within 4 weeks prior to the first study dose 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 study entry
- 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
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