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TerminatedNCT05191797Updated Sep 26, 2024Results posted

Bomedemstat and Maintenance Immunotherapy for Treatment of Newly Diagnosed Extensive Stage Small Cell Lung Cancer

A Phase 1/2 interventional study of Bomedemstat and Atezolizumab in Extensive Stage Lung Small Cell Carcinoma and Limited Stage Lung Small Cell Carcinoma, sponsored by University of Washington. Terminated at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-26.

Sponsored by University of Washington · Phase 1/2, Interventional, and Treatment

Why this study was terminated
Closed per SRC Low Accrual Policy
Phase
Phase 1/2
Study type
Interventional
Enrollment
3
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study summary

This phase I/II trial studies the side effects of bomedemstat and maintenance immunotherapy with atezolizumab and to see how well they work in treating patients with newly diagnosed extensive stage small cell lung cancer. Bomedemstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving bomedemstat and atezolizumab may work better in treating patients with extensive stage small cell lung cancer.

Read the detailed description

OUTLINE:

Patients receive bomedemstat orally (PO) once daily (QD) on days 1-21 and atezolizumab intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 12 weeks thereafter.

02

Conditions studied

  • Extensive Stage Lung Small Cell Carcinoma
  • Limited Stage Lung Small Cell Carcinoma

Keywords

  • Lung
03

In context

Lead sponsor

University of Washington is the lead sponsor of 1,431 studies on the registry; 226 are open to participants now.

Of its 158 completed or terminated interventional studies of FDA-regulated products, 136 (86%) have results posted.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Adult aged 18 years or older and willing and able to provide written informed consent
  • Histologically confirmed diagnosis of extensive stage small-cell lung cancer (ES-SCLC)

    • Note: Previously treated limited stage SCLC (LS-SCLC) patients are eligible if disease progression had occurred following completion of definitive treatment for LS-SCLC. Determination of disease progression after prior therapy for LS-SCLC is at the discretion of the investigator
  • Having received four cycles of platinum-etoposide concurrent with three or four cycles of immune checkpoint inhibitor as induction systemic therapy for ES-SCLC immediately prior to study enrollment (see below for definitions). Note that immune checkpoint inhibitor may have been omitted from the first cycle only

    • Platinum is defined as cisplatin or carboplatin. Immune checkpoint inhibitor is defined as atezolizumab, durvalumab, or other anti-PDL1 or anti-PD1 monoclonal antibody that is approved by the United States (US) Food and Drug Administration for first-line treatment of ES-SCLC in combination with platinum and etoposide at the time of treatment receipt. Immediately prior is defined as receipt of cycle 1 day 1 of platinum-etoposide +/- immune checkpoint inhibitor no more than 112 days prior to cycle 1 day 1 of study treatment, and administration of fourth cycle of platinum-etoposide and immune checkpoint inhibitor no more than 30 days prior to cycle 1 day 1 of study treatment
  • Eligible to receive maintenance atezolizumab, as defined by stable disease or better, following induction platinum-etoposide and immune checkpoint inhibitor. Determination of response to induction therapy is at the discretion of the investigator. Investigators should contact the principal investigator (PI) if clarification is needed
  • Eastern Cooperative Oncology Group (ECOG performance status of =\< 2)
  • Minimum life expectancy of >= 12 weeks

    • Note: myeloid growth factor use within 14 days of study treatment initiation is not permitted. Growth factor may have been previously administered during induction chemoimmunotherapy
  • Platelet count (Plt) >= 75 x 10\^3/mcL (without transfusion)
  • Hemoglobin (Hgb) >= 8.0 g/dL (transfusion is permitted)
  • Calculated glomerular filtration rate (GFR; using the Cockcroft-Gault equation) >= 40 mL/min or serum creatinine =\< 1.5 x upper limit of normal
  • Serum total bilirubin =\< 1.5 x upper limit of normal (ULN) or =\< 3 x ULN for subjects with Gilbert's disease
  • Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =\< 2.5 x ULN (=\< 5 x ULN if evidence of hepatic involvement by malignant disease)
  • International normalized ratio (INR) \< 1.5 x upper limit of normal (only in patients not receiving anticoagulant agents at baseline)

    • Note: there is no INR or activated partial thromboplastin time (aPTT) threshold for patients who are receiving anticoagulant agents at baseline, but patients must be on a stable dose of anticoagulant, and discontinuation of all anticoagulation while the platelet count is below 50 x 10\^3/mcL must be deemed appropriate for the patient by the investigator prior to enrollment
  • Activated partial thromboplastin time (aPTT) \< 1.5 x the local upper limit of normal (only in patients not receiving anticoagulant agents at baseline)

    • Note: there is no INR or aPTT threshold for patients who are receiving anticoagulant agents at baseline, but patients must be on a stable dose of anticoagulant, and discontinuation of all anticoagulation while the platelet count is below 50 x 10\^3/mcL must be deemed appropriate for the patient by the investigator prior to enrollment
  • Able to swallow capsules
  • Amenable to peripheral blood sampling during the study
  • Female subjects of childbearing potential should be willing to use 2 methods of birth control or abstain from heterosexual activity for the course of the study through 28 days after the last dose of study medication. Subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
  • Male subjects who are sexually active with female partner(s) of childbearing potential should be willing to use an adequate method of contraception starting with the first dose of study therapy through 28 days after the last dose of study therapy

Exclusion criteria

Exclusion Criteria:

  • Prior receipt of systemic therapy for ES-SCLC other than four cycles of induction platinum-etoposide and immune checkpoint inhibitor
  • Diagnosis of LS-SCLC that has not been previously treated
  • Receipt of radiation therapy for symptomatic deterioration and/or radiographic disease progression that was administered after initiation of induction platinum-etoposide and immune checkpoint inhibitor. Note: the presence of untreated asymptomatic brain metastasis, or a history of receipt of radiation to brain metastasis that was not initiated in response to symptomatic deterioration and/or radiographic disease progression following initiation of induction systemic therapy, does not preclude study participation. Investigators should contact the PI if clarification is needed
  • Anticipated use of prophylactic cranial irradiation or consolidative thoracic radiation therapy during study participation. Note: Palliative radiation to the central nervous system (CNS) for new CNS disease that develops during study participation is allowed
  • History of prior immune-related adverse event or other toxicity associated with immune checkpoint inhibitor that precludes safe administration of maintenance atezolizumab, in the opinion of the investigator
  • Current or prior use of immunosuppressive medication within 14 days prior to the first dose of study treatment. The following are exceptions to this criterion:

    • Intranasal, inhaled, topical steroids or local steroid injections (e.g., intra-articular injection)
    • Systemic corticosteroids at doses not to exceed 10 mg/d of prednisone or equivalent
    • Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication)
  • Active autoimmune disease requiring systemic immunosuppression or history of autoimmune disease requiring systemic immunosuppression within the last 2 years

    • Note: Systemic immunosuppression should be interpreted as systemic glucocorticoids at a dose of greater than 10 mg/day of prednisone or equivalent, systemic biologic agents including monoclonal antibodies against inflammatory mediators, or small molecule agents. Investigators should contact the PI if clarification is needed
  • Active pneumonitis or interstitial lung disease (ILD), or a history of pneumonitis/ILD, which required systemic immunosuppression (e.g. corticosteroids)
  • Known bleeding disorder (e.g., dysfibrinogenaemia, factor IX deficiency, hemophilia, Von Willebrand's disease, disseminated intravascular coagulation [DIC], fibrinogen deficiency, or other clotting factor deficiency), at the discretion of the investigator
  • History of severe thrombocytopenia or platelet dysfunction (e.g. immune thrombocytopenic purpura), at the discretion of the investigator
  • Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to bomedemstat or LSD1 inhibitors (i.e., monoamine oxidase inhibitors; MAOIs) that contraindicates their participation
  • Any hypersensitivity to PD-1/PD-L1 targeting agents
  • Current use of monoamine oxidase A and B inhibitors (MAOIs)
  • Current use of a prohibited medication (e.g. romiplostim) or expected to require any of these medications during treatment with the investigational drug
  • Current or anticipated use of an antiplatelet (e.g. clopidogrel), anticoagulant (e.g. warfarin or apixaban), or nonsteroidal anti-inflammatory drug (NSAID) with antiplatelet activity (e.g. aspirin, ibuprofen), that, in the opinion of the investigator, could NOT be safely discontinued when the subject's platelet count decreases below 50 x 10\^3/mcL
  • Has undergone major surgery within 4 weeks prior to starting study drug and/or has not recovered from side effects of such surgery. Note: Major surgery and recovery are defined at the discretion of the investigator
  • Receipt of a live vaccine within 30 days of first dose of study therapy
  • Uncontrolled active infection
  • Any concomitant active malignancy considered clinically significant by the investigator
  • Known human immunodeficiency virus (HIV) infection or known active hepatitis B or hepatitis C virus infection (testing will not be conducted as part of screening procedures)
  • History of any illness/impairment of gastrointestinal (GI) function that might interfere with drug absorption (e.g. chronic diarrhea), confound the study results or pose an additional risk to the patient by participation in the study
  • Use of an investigational agent within 28 days, or the equivalent of at least 7 half-lives of that agent, whichever is the shorter, prior to the study day 1
  • Females who are pregnant or breastfeeding or plan to become pregnant or breastfeed at any time during the study
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
3 participants (actual)

Study arms

  • Experimental
    Treatment (bomedemstat, atezolizumab)

    Patients receive bomedemstat PO QD on days 1-21 and atezolizumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

    Drug: Bomedemstat · Biological: Atezolizumab

Interventions

  • Given PO

    Also known as: 1990504-34-1, IMG 7289, IMG-7289, LSD-1 Inhibitor IMG-7289, Lysine-specific Demethylase 1 Inhibitor IMG-7289

  • BiologicalAtezolizumab

    Given IV

    Also known as: 1380723-44-3, Immunoglobulin G1, Anti-(human CD Antigen cd274) (Human Monoclonal MPDL3280A Heavy Chain), Disulfide with Human Monoclonal MPDL3280A Kappa-chain, Dimer, MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, Tecentriq

06

What researchers measure

Primary outcomes

  1. Number of Participants Experiencing a Dose Limiting Toxicity (DLT)

    DLT to bomedemstat combined with atezolizumab is defined as the occurrence of any of the following toxicities by CTCAE 5.03 determined to be possibly, probably, or likely related to bomedemstat or atezolizumab occurring within 21 days of initiation of treatment. The specific events are: \- Grade 4 non-hematologic toxicity (not laboratory). * Grade 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care. * Any Grade 3 or Grade 4 non-hematologic laboratory value if: * Medical intervention is required to treat the patient, or * The abnormality leads to hospitalization * Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding event or the need for prophylactic transfusions). * Febrile neutropenia. * Grade 5 toxicity.

    Time frame: Up to 21 days from initiation of treatment

  2. Progression Free Survival

    Distributions for time-to-event outcomes will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.

    Time frame: From the date of study enrollment up to 2 years

  3. Incidence Patients Experiencing Adverse Events

    Only adverse events that meet the following definition will be recorded: 1. All grade 3 and higher adverse events 2. Grade 1-2 adverse events that require medical intervention, i.e. initiation of a new medication, or are otherwise clinically significant at the discretion of the investigator 3. Any adverse event that requires a dose reduction or dose delay of either bomedemstat or atezolizumab Adverse events will be recorded from Cycle 1 Day 1 until the Safety Monitoring visit performed according to the Study Calendar (Section 7.0), using the Adverse Event case report forms/worksheets. For subjects who discontinue study therapy for a reason other than disease progression and are being followed with Monitoring visits (Section 8.5.3.3), adverse events should continue to be monitored. Adverse events related to either bomedemstat or atezolizumab will be followed until resolution or stabilization of the AE or until the beginning of a new anti-neoplastic therapy, whichever occurs first.

    Time frame: From initial of treatment, up to 30 days after discontinuation of study treatment, up to 7 months

Secondary outcomes

  1. Overall Survival

    Distributions for time-to-event outcomes will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.

    Time frame: From the date of study enrollment until death from any cause up to 2 years

07

Results

Posted Sep 26, 2024

Participant flow

Participant flow — Overall Study
MilestoneTreatment (Bomedemstat, Atezolizumab)
Started3
Completed3
Not completed0

Outcome measures

PrimaryNumber of Participants Experiencing a Dose Limiting Toxicity (DLT)

DLT to bomedemstat combined with atezolizumab is defined as the occurrence of any of the following toxicities by CTCAE 5.03 determined to be possibly, probably, or likely related to bomedemstat or atezolizumab occurring within 21 days of initiation of treatment. The specific events are: \- Grade 4 non-hematologic toxicity (not laboratory). * Grade 3 non-hematologic toxicity (not laboratory) lasting \>3 days despite optimal supportive care. * Any Grade 3 or Grade 4 non-hematologic laboratory value if: * Medical intervention is required to treat the patient, or * The abnormality leads to hospitalization * Thrombocytopenia leading to clinically significant sequelae (i.e., a clinically significant bleeding event or the need for prophylactic transfusions). * Febrile neutropenia. * Grade 5 toxicity.

Time frame:
Up to 21 days from initiation of treatment
Reported as:
Count of participants · Participants
Number of Participants Experiencing a Dose Limiting Toxicity (DLT)
ParticipantsTreatment (Bomedemstat, Atezolizumab)
Number of Participants Experiencing a Dose Limiting Toxicity (DLT)0
PrimaryProgression Free Survival

Distributions for time-to-event outcomes will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% confidence interval (CI) will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.

Time frame:
From the date of study enrollment up to 2 years
Reported as:
Median · months
Progression Free Survival
monthsTreatment (Bomedemstat, Atezolizumab)
Progression Free Survival3.82 (1.53 to 6.11)
PrimaryIncidence Patients Experiencing Adverse Events

Only adverse events that meet the following definition will be recorded: 1. All grade 3 and higher adverse events 2. Grade 1-2 adverse events that require medical intervention, i.e. initiation of a new medication, or are otherwise clinically significant at the discretion of the investigator 3. Any adverse event that requires a dose reduction or dose delay of either bomedemstat or atezolizumab Adverse events will be recorded from Cycle 1 Day 1 until the Safety Monitoring visit performed according to the Study Calendar (Section 7.0), using the Adverse Event case report forms/worksheets. For subjects who discontinue study therapy for a reason other than disease progression and are being followed with Monitoring visits (Section 8.5.3.3), adverse events should continue to be monitored. Adverse events related to either bomedemstat or atezolizumab will be followed until resolution or stabilization of the AE or until the beginning of a new anti-neoplastic therapy, whichever occurs first.

Time frame:
From initial of treatment, up to 30 days after discontinuation of study treatment, up to 7 months
Reported as:
Count of participants · Participants
Incidence Patients Experiencing Adverse Events
ParticipantsTreatment (Bomedemstat, Atezolizumab)
Elevated Creatinine1
Transaminitis1
Syncope1
H. Pylori1
Fatigue1
Shingles1
Maculopapular Rash1
Left Lower Extremity Pain1
Left Lower Extremity Weaskness1
SecondaryOverall Survival

Distributions for time-to-event outcomes will be evaluated using the method of Kaplan-Meier. For point estimates at landmark times, the associated 95% CI will be calculated using Greenwood's formula and based on a log-log transformation applied on the survival function.

Time frame:
From the date of study enrollment until death from any cause up to 2 years
Reported as:
Median · Months
Overall Survival
MonthsTreatment (Bomedemstat, Atezolizumab)
Overall Survival15.1 (6.56 to 23.64)

Adverse events

Collected over All-Cause Mortality was monitored for up to 2 years; serious and/or other adverse events were assessed up to 1 year, 3 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Treatment (Bomedemstat, Atezolizumab)3/3 (100%)0/3 (0%)3/3 (100%)
Most frequent other events
Most frequent other events
EventTreatment (Bomedemstat, Atezolizumab)
Elevated CreatinineInvestigations1/3
TransaminitisInvestigations1/3
SyncopeNervous system disorders1/3
H. PyloriGastrointestinal disorders1/3
FatigueGeneral disorders1/3
ShinglesInfections and infestations1/3
Maculopapular RashSkin and subcutaneous tissue disorders1/3
Left Lower Extremity PainMusculoskeletal and connective tissue disorders1/3
Left Lower Extremity WeaknessMusculoskeletal and connective tissue disorders1/3

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)Treatment (Bomedemstat, Atezolizumab)
<=18 years0
Between 18 and 65 years2
>=65 years1
Age, Continuous
Age, Continuous(Years)Treatment (Bomedemstat, Atezolizumab)
Median63 (58 to 67)
Sex: Female, Male
Sex: Female, Male(Participants)Treatment (Bomedemstat, Atezolizumab)
Female2
Male1
Race (NIH/OMB)
Race (NIH/OMB)(Participants)Treatment (Bomedemstat, Atezolizumab)
American Indian or Alaska Native0
Asian1
Native Hawaiian or Other Pacific Islander0
Black or African American0
White2
More than one race0
Unknown or Not Reported0
Region of Enrollment
Region of Enrollment(participants)Treatment (Bomedemstat, Atezolizumab)
United States3
08

Study locations

1 site
  • Fred Hutch/University of Washington Cancer Consortium
    Seattle, Washington 98109, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jan 6, 2023
  • Informed consent form · Jan 6, 2023

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Sep 26, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT05191797
Responsible party
Rafael Santana-Davila (Associate Professor, University of Washington) — Principal investigator
First posted
Jan 14, 2022
Start date
Apr 11, 2022
Primary completion
Aug 3, 2023
Completion
Apr 5, 2024
Results posted
Sep 26, 2024
Last update
Sep 26, 2024

Study contacts

Rafael Santana-Davila
principal investigator · Fred Hutch/University of Washington Cancer Consortium

Oversight

Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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Studies of the drug tested here: Bomedemstat

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