Radar des Essais Cliniques

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