Bomedemstat + Immunotherapy for Small Cell Lung Cancer

Overseen By Rebecca Wood

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of Washington

Must be taking: Platinum-etoposide, Immune checkpoint inhibitors

Must not be taking: MAOIs, Antiplatelets, Anticoagulants, NSAIDs

Disqualifiers: Untreated infection, Active autoimmune, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 21 days per cycle

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of a new drug, bomedemstat, combined with immunotherapy, for people with extensive stage small cell lung cancer. Researchers aim to determine if this combination can halt the growth and spread of cancer cells more effectively than current treatments. It suits individuals diagnosed with extensive stage small cell lung cancer who have completed certain initial treatments. As a Phase 1, Phase 2 trial, this research focuses on understanding how the treatment works in people and measuring its effectiveness in an initial, smaller group.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, you cannot use certain medications like monoamine oxidase inhibitors (MAOIs) or some blood thinners during the trial. It's best to discuss your current medications with the trial team to see if any adjustments are needed.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that bomedemstat is usually well-tolerated. A previous study found it safe for patients with acute leukemia, with no severe side effects reported. Another study suggests it should also be well-tolerated in people with small cell lung cancer (SCLC).

For atezolizumab, studies indicate it has a good safety record. In one trial, patients received it with chemotherapy for SCLC and tolerated it well. Common side effects included tiredness and nausea, but these were manageable.

Both bomedemstat and atezolizumab have shown promising safety results in earlier studies. However, like any treatment, risks exist. Discussing experiences with a doctor can help determine if joining a trial is a good choice. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Bomedemstat is unique because it targets an enzyme called LSD1, which plays a role in cancer cell growth, while traditional treatments for small cell lung cancer, like chemotherapy and radiation, attack rapidly dividing cells in a more general way. This targeted approach could potentially offer a more precise attack on cancer cells with fewer side effects. Researchers are excited because bomedemstat, when combined with the immunotherapy drug atezolizumab, may enhance the body's immune response against cancer, offering a new avenue for treatment that could improve outcomes for patients.

What evidence suggests that bomedemstat and atezolizumab might be effective for small cell lung cancer?

Research shows that bomedemstat can make small cell lung cancer (SCLC) more responsive to treatments that enhance the immune system's ability to fight cancer. Studies have found that it increases certain proteins on cancer cells, making it easier for the immune system to identify and attack them. In this trial, participants will receive a combination of bomedemstat and atezolizumab. Atezolizumab, an immunotherapy, has already extended life expectancy for SCLC patients when used with chemotherapy, with more patients living longer compared to those who didn’t receive it. Together, bomedemstat and atezolizumab may provide a stronger defense against cancer by enhancing the body's immune response. ^{2 3 4 6 7}

Who Is on the Research Team?

Rafael Santana-Davila

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Are You a Good Fit for This Trial?

Adults over 18 with newly diagnosed extensive stage small cell lung cancer (ES-SCLC) who've completed initial chemoimmunotherapy and are eligible for maintenance atezolizumab. They must have a life expectancy of at least 12 weeks, adequate organ function, no prior ES-SCLC systemic therapy other than specified treatments, and not be pregnant or breastfeeding. Participants should agree to contraception use and not have certain autoimmune diseases or hypersensitivities.

Inclusion Criteria

I can swallow pills.

I recently started treatment with specific drugs for small cell lung cancer.

I had small cell lung cancer treatment and it came back after finishing treatment.

Exclusion Criteria

You are allergic to PD-1/PD-L1 targeting drugs.

I do not have any ongoing infections that aren't responding to treatment.

I have not received a live vaccine in the last 30 days.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bomedemstat orally once daily on days 1-21 and atezolizumab intravenously on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.

21 days per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion, with follow-up at 30 days and then every 12 weeks thereafter.

Up to 2 years

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Bomedemstat

Trial Overview The trial is testing bomedemstat in combination with the immunotherapy drug atezolizumab to see if they're more effective for treating ES-SCLC. Bomedemstat may halt tumor growth by inhibiting enzymes needed for cell proliferation while atezolizumab could boost the immune system's ability to fight cancer.

How Is the Trial Designed?

Group I: Treatment (bomedemstat, atezolizumab) Experimental Treatment 2 Interventions

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.

Who Is Running the Clinical Trial?

University of Washington

Lead Sponsor

Trials

1,858

Recruited

2,023,000+

Imago BioSciences,Inc.

Industry Sponsor

Trials

10

Recruited

380+

Imago BioSciences, Inc., a subsidiary of Merck & Co., Inc., (Rahway, New Jersey USA)

Industry Sponsor

Trials

10

Recruited

380+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a four-year study of 80 patients with non-small cell lung cancer treated with anti-PD-1 and anti-PD-L1 therapies, significant overall survival rates were observed, particularly with nivolumab and pembrolizumab, showing 79.7% survival at 6 months and 100% at first-line treatment for pembrolizumab.

Adverse events were common, occurring in over 84% of patients, with fatigue and respiratory issues being the most reported, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and safety of anti PD-1/PD-L1 antibodies as monotherapy in patients with non-small-cell lung cancer. Zayas-Soriano, M., Bonete-Sánchez, M., Campillo-López, J., et al.[2021]

SP-2577 (Seclidemstat), an inhibitor of the KDM1A enzyme, showed statistically significant growth inhibition in some pediatric sarcoma xenografts, particularly in the RMS Rh10 model, but overall had limited activity across the tested models.

Despite some inhibition of tumor growth, SP-2577 did not lead to tumor regressions or consistent changes in key histone modifications or tumor characteristics, indicating that its efficacy may be modest at the evaluated dose and schedule.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In vivo evaluation of the lysine-specific demethylase (KDM1A/LSD1) inhibitor SP-2577 (Seclidemstat) against pediatric sarcoma preclinical models: A report from the Pediatric Preclinical Testing Consortium (PPTC). Kurmasheva, RT., Erickson, SW., Han, R., et al.[2023]

Immune checkpoint inhibitors targeting PD-1/PD-L1 have been approved by the FDA for lung cancer treatment, either alone or in combination with other therapies, significantly improving patient outcomes.

The use of these immunotherapies has transformed lung cancer treatment, offering long-term benefits for selected patients, although ongoing research is needed to identify reliable biomarkers for better patient selection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met? Kaen, DL., Minatta, N., Russo, A., et al.[2022]

Iadademstat, a selective LSD1 inhibitor, was found to be safe and well-tolerated in a phase I trial involving 27 patients with relapsed/refractory acute myeloid leukemia (R/R AML), with a recommended dose of 140 µg/m2/d established for further treatment.

The treatment showed promising signs of efficacy, including reductions in blood and bone marrow blast percentages and one complete remission, particularly in patients with MLL/KMT2A-rearranged AML, indicating its potential as a therapeutic option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

First-in-Human Phase I Study of Iadademstat (ORY-1001): A First-in-Class Lysine-Specific Histone Demethylase 1A Inhibitor, in Relapsed or Refractory Acute Myeloid Leukemia. Salamero, O., Montesinos, P., Willekens, C., et al.[2021]

In castrate resistant prostate cancer (CRPC) models driven by the AR-V7 variant, inhibiting the enzyme LSD1 significantly reduced activation of both the wild type and AR-V7 forms of the androgen receptor.

This study suggests that targeting LSD1 could be a promising therapeutic strategy for treating CRPC, as it plays a role in the activation of androgen receptors that contribute to cancer progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models. Regufe da Mota, S., Bailey, S., Strivens, RA., et al.[2022]

In a phase I/IIA study involving 22 treatment-naive patients with extensive-stage small-cell lung cancer, the maximum-tolerated dose of pomalidomide was determined to be 4 mg/day, with common side effects including fatigue, nausea, and neutropenia.

While the combination of pomalidomide with cisplatin and etoposide was found to be safe, it did not enhance the effectiveness of chemotherapy alone, as indicated by an overall response rate of only 31.8% and a median overall survival of 49.6 weeks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase I study of pomalidomide (CC-4047) in combination with cisplatin and etoposide in patients with extensive-stage small-cell lung cancer. Ellis, PM., Jungnelius, U., Zhang, J., et al.[2022]

Citations

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IMpower133 efficacy results in 1L ES-SCLC Adding TECENTRIQ® (atezolizumab) to carbo/etop significantly improved median PFS1. 5.2-month median PFS vs 4.3 months with placebo + carbo/etop (HR=0.77*; ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37871898/

The Real-World Outcome of First Line Atezolizumab in ... We provided evidence of the favorable real-world effectiveness and safety of atezolizumab plus chemotherapy in ES-SCLC patients.

3. nejm.org nejm.org/doi/full/10.1056/NEJMoa1809064

First-Line Atezolizumab plus Chemotherapy in Extensive- ... Despite response rates of 60 to 65%, limited progress has been made in more than two decades; outcomes remain poor, with a median overall ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S0169500223009170

Results of the IFCT-1905 CLINATEZO real-world study Small cell lung cancer (SCLC) is a highly aggressive type of lung cancer. · Atezolizumab plus chemotherapy improves overall survival in 1st-line treatment of ...

5. tecentriq.com tecentriq.com/sclc/results/how-tecentriq-may-help.html

Imagine if you had more time to live your life More patients lived longer with TECENTRIQ + chemotherapy ... Median overall survival (OS) was 12.3 months for patients taking TECENTRIQ® (atezolizumab.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11880126/

Efficacy and safety analysis of atezolizumab continuation ... The IMpower 133 trial demonstrated that combining atezolizumab with chemotherapy significantly enhanced survival, establishing chemo-immunotherapy as the ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39306923/

Five-year survival in patients with extensive-stage small ... The three-, four-, and five-year overall survival (95 % CI) estimates were 16 % (11 %-21 %), 13 % (8 %-18 %), and 12 % (7 %-17 %), respectively. In IMbrella A, ...