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

NCT05191797 | Terminated Phase 1 Results DMC FDA Drug

• 4 other identifiers: RG1122005NCI-2021-13863P50CA22894410841
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Extensive Stage Lung Small Cell Carcinoma; Limited Stage Lung Small Cell Carcinoma

Keywords

Lung

Outcome Measures

Primary Outcomes (3)

• 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.

  Up to 21 days from initiation of treatment

• 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.

  From the date of study enrollment up to 2 years

• 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.

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

Secondary Outcomes (1)

• Overall Survival

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

Study Arms (1)

Treatment (bomedemstat, atezolizumab)

EXPERIMENTAL

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

Bomedemstat DRUG

Given PO

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

Treatment (bomedemstat, atezolizumab)

Atezolizumab BIOLOGICAL

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

Treatment (bomedemstat, atezolizumab)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Washington: lead
• National Cancer Institute (NCI): collaborator
• Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA): collaborator

Study Sites (1)

Fred Hutch/University of Washington Cancer Consortium

Seattle, Washington, 98109, United States

Location

MeSH Terms

Interventions

bomedemstat; atezolizumab; Immunoglobulin G; Disulfides

Intervention Hierarchy (Ancestors)

Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Sulfides; Anions; Ions; Electrolytes; Inorganic Chemicals; Hydrogen Sulfide; Sulfur Compounds; Organic Chemicals

Results Point of Contact

• Title: Rafael Santana-Davila
• Organization: University of Washington

rafaelsd@uw.edu

2066062190

Study Officials

• Rafael Santana-Davila

  Fred Hutch/University of Washington Cancer Consortium

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: December 29, 2021
• First Posted: January 14, 2022
• Study Start: April 11, 2022
• Primary Completion: August 3, 2023
• Study Completion: April 5, 2024
• Last Updated: September 26, 2024
• Results First Posted: September 26, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)