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

3 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Bomedemstat + Immunotherapy for Small Cell Lung Cancer?

Research shows that LSD1 inhibitors, like Bomedemstat, have shown promising activity against small cell lung cancer (SCLC) by targeting specific cancer cell pathways and potentially overcoming resistance to other treatments. However, their effectiveness may vary depending on the specific characteristics of the cancer cells. ^{1 2 3 4 5}

Is the combination of Bomedemstat and immunotherapy safe for humans?

Bomedemstat, also known as IMG-7289, is an LSD1 inhibitor that has been studied for safety in various cancer types, including small cell lung cancer and acute myeloid leukemia. While specific safety data for the combination with immunotherapy is not provided, LSD1 inhibitors like Bomedemstat have shown potential as cancer treatments in clinical trials, indicating a level of safety in humans. ^{4 6 7 8 9}

What makes the drug Bomedemstat unique for treating small cell lung cancer?

Bomedemstat is unique because it is a LSD1 inhibitor, which targets epigenetic changes in cancer cells, potentially offering a new approach compared to traditional chemotherapy or immunotherapy alone. This drug is combined with immunotherapy to enhance the immune system's ability to fight cancer, which is a novel strategy for small cell lung cancer. ^{10 11 12 13 14}

What is the purpose of this trial?

This trial studies how well bomedemstat and atezolizumab work together in treating patients with severe small cell lung cancer. Bomedemstat blocks enzymes to stop cancer growth, while atezolizumab helps the immune system fight the cancer. Atezolizumab has been shown to improve survival in various types of lung cancer, including non-small cell lung cancer and small cell lung cancer, often in combination with chemotherapy.

Research Team

Rafael Santana-Davila

Principal Investigator

Fred Hutch/University of Washington Cancer Consortium

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Intrinsic and acquired drug resistance to LSD1 inhibitors in small cell lung cancer occurs through a TEAD4-driven transcriptional state. [2022]

2. United States pubmed.ncbi.nlm.nih.gov

Antitumor activity of LSD1 inhibitors in lung cancer. [2020]

3. England pubmed.ncbi.nlm.nih.gov

LSD1/KDM1A inhibitors in clinical trials: advances and prospects. [2023]

4. England pubmed.ncbi.nlm.nih.gov

LSD1 inhibition attenuates androgen receptor V7 splice variant activation in castration resistant prostate cancer models. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Targeting NOTCH activation in small cell lung cancer through LSD1 inhibition. [2020]

6. United States 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. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

LSD1 activates a lethal prostate cancer gene network independently of its demethylase function. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Discovery of CC-90011: A Potent and Selective Reversible Inhibitor of Lysine Specific Demethylase 1 (LSD1). [2021]

9. United States 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). [2023]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Immunomodulation of HDAC Inhibitor Entinostat Potentiates the Anticancer Effects of Radiation and PD-1 Blockade in the Murine Lewis Lung Carcinoma Model. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Immunotherapy in Lung Cancer: Are the Promises of Long-Term Benefit Finally Met? [2022]

12. United States 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. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Pre-clinical studies of epigenetic therapies targeting histone modifiers in lung cancer. [2021]

14. Spain 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. [2021]