Clinical Trial 23584

• Overview

  Study Title:

  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

  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.

  Objective:

  Primary Objectives * To compare the progression-free survival (PFS) between the combination of iadademstat plus immune checkpoint inhibitor (ICI) versus ICI maintenance alone. Secondary Objectives * To compare objective response rate (ORR) and overall survival (OS) between treatment arms. * To evaluate the safety of combination iadademstat plus ICI.

• Treatments

  Therapies:

  lysine specific demethylase-1 inhibitor; monoclonal antibody

  Medications:

  AMP-514 (Durvalumab); Atezolizumab (Tecentriq); Durvalumab (); Iadademstat (); MEDI4736 (Durvalumab)

• Inclusion Criteria

  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) with CT scan, MRI, or calipers by clinical exam
  • 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 or older.
  • Body weight 50 kg or more
  • Patient is able to swallow oral medications
  • Eastern Cooperative Oncology Group (ECOG) performance status 2 or less (Karnofsky 60% or greater). This assessment for eligibility will take place after patients have received 4 cycles of standard of care (SOC) chemotherapy-ICI
  • Adequate organ function
  • 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. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause.
  • Pregnant women are excluded from this study because atezolizumab and durvalumab are monoclonal antibody agents with the potential for teratogenic or abortifacient effects.
  • 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.
  • Other criteria may apply

• Exclusion Criteria

  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 or above 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 or above 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]-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 cycle 1, day 1 or anticipation of need for systemic immunosuppressive medication during 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)
  • 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.
  • 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 > 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
  • Other criteria may apply

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