Iadademstat + Atezolizumab/Durvalumab for Small Cell Lung Cancer

Recruiting at 42 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: National Cancer Institute (NCI)

Must be taking: Platinum etoposide chemotherapy

Must not be taking: Antidepressants, Immunosuppressives

Disqualifiers: Autoimmune disease, Organ transplant, others

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

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 12

45 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for small cell lung cancer that has spread beyond the lungs. It combines iadademstat, a drug that may block tumor growth, with existing immunotherapies—atezolizumab (Tecentriq) or durvalumab (Imfinzi)—which help the immune system fight cancer. The goal is to determine the safest dose and assess whether this combination can better control cancer compared to immunotherapy alone. Suitable candidates for this trial include those with extensive-stage small cell lung cancer who have already received chemotherapy and immunotherapy. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, such as specific anti-depressants (tranylcypromine or phenelzine) and any immunosuppressive or immunostimulatory agents. Additionally, herbal and natural remedies, as well as complementary or alternative medicines, must be stopped at least one week before starting the study treatment.

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

Research has shown that iadademstat is being tested with atezolizumab or durvalumab to assess their safety and side effects. Early results suggest these combinations are generally well-tolerated.

Atezolizumab and durvalumab are types of immunotherapy that help the immune system fight cancer. They can have side effects, but these are usually manageable. Iadademstat is a newer drug under study for its potential to stop tumor growth.

Since this study is in its early stages, it focuses on understanding the safety of this combination and determining the best dose. Researchers closely monitor for any side effects. Participants in the trial will have regular check-ups to monitor health and any possible side effects.

While safety cannot be guaranteed, the trial aims to carefully manage and communicate any risks. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Iadademstat for small cell lung cancer because it targets a specific enzyme called LSD1, which is involved in cancer cell growth. This mechanism is unique compared to the standard immunotherapy treatments like atezolizumab and durvalumab, which work by boosting the immune system to attack cancer cells. By inhibiting LSD1, Iadademstat may directly halt cancer progression at the cellular level, offering a new approach to treatment. Additionally, combining Iadademstat with existing immunotherapies could enhance their effectiveness, potentially leading to better outcomes for patients.

What evidence suggests that this trial's treatments could be effective for small cell lung cancer?

Research shows that adding iadademstat to the immunotherapy drugs atezolizumab or durvalumab might control small cell lung cancer (SCLC) for a longer duration than using either drug alone. In this trial, one group of participants will receive iadademstat combined with either atezolizumab or durvalumab, while another group will continue with atezolizumab or durvalumab alone. Iadademstat blocks certain enzymes that cancer cells need for growth. Early results suggest this combination could be promising for treating extensive-stage SCLC, where the cancer has spread beyond the lungs. Atezolizumab and durvalumab help the body's immune system attack cancer cells. Combining iadademstat with these drugs could enhance this effect and help prevent further cancer spread. ^{1 3 4 6 7}

Who Is on the Research Team?

Charles M Rudin

Principal Investigator

JHU Sidney Kimmel Comprehensive Cancer Center LAO

Are You a Good Fit for This Trial?

This trial is for adults over 18 with small cell lung cancer that has spread and responded to initial chemo and immunotherapy. Participants must have a measurable tumor, weigh at least 50 kg, be able to swallow pills, and have an ECOG performance status of ≤2.

Inclusion Criteria

I can take pills by mouth.

My white blood cell count is healthy.

My lung cancer is confirmed to be small cell type.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase I Treatment

Patients receive iadademstat orally and continue receiving their initial ICI treatment. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

4 visits (in-person) per cycle

Phase II Treatment

Patients are randomized to receive either iadademstat with ICI or ICI alone. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

28 days per cycle

4 visits (in-person) per cycle

Follow-up

Participants are monitored for safety and effectiveness after treatment completion. Follow-up includes CT scans and blood and urine sample collection.

12 months

Every 3 months

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Durvalumab
• Iadademstat

Trial Overview The trial tests the safety and optimal dose of Iadademstat combined with Atezolizumab or Durvalumab in patients with extensive stage small cell lung cancer. It aims to see if this combination can better control cancer than the standard treatments alone.

How Is the Trial Designed?

Group I: Phase II, Arm I (iadademstat, atezolizumab, durvalumab) Experimental Treatment 9 Interventions

Patients in Phase II Arm I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Group II: Phase I (iadademstat, atezolizumab, durvalumab) Experimental Treatment 9 Interventions

Patients in Phase I receive iadademstat PO on days 1, 8, 15, and 22 or days 1 and 15 of each cycle. Patients also continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Group III: Phase II Arm II (atezolizumab, durvalumab) Active Control 8 Interventions

Patients in Phase II Arm II continue receiving their initial ICI treatment, either atezolizumab IV over 30-60 minutes on day 1 of each cycle or durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo MUGA or ECHO, brain MRI or brain CT during screening, and CT scans and blood and urine sample collection throughout the trial. Patients may also undergo an optional tumor biopsy on study.

Iadademstat is already approved in United States, European Union for the following indications:

Approved in United States as Iadademstat for:

• Orphan drug designation for Acute Myeloid Leukemia (AML)

Approved in European Union as Iadademstat for:

• Orphan drug designation for Acute Myeloid Leukemia (AML)

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a phase 1 study involving 17 patients with relapsed or refractory small-cell lung cancer (SCLC), atezolizumab was generally well tolerated, with 64.7% experiencing any-grade treatment-related adverse events, the most common being fatigue.

Atezolizumab showed some antitumor activity, with a partial response in 5.9% of patients and a median overall survival of 5.9 months, suggesting potential benefits for patients with high T-effector gene signature and PD-L1 expression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. Chiang, AC., Sequist, LVD., Gilbert, J., et al.[2021]

Durvalumab, while effective for extensive-stage small-cell lung cancer, is not cost-effective compared to atezolizumab, with an incremental cost-effectiveness ratio (ICER) of $165,182 per quality-adjusted life-year (QALY), exceeding the typical willingness-to-pay threshold of $150,000.

The analysis, based on data from two phase 3 clinical trials, suggests that reducing the cost of durvalumab or increasing the willingness-to-pay threshold could improve its cost-effectiveness relative to atezolizumab.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cost-Effectiveness Analysis of Atezolizumab Versus Durvalumab as First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer in the USA. Ionova, Y., Vuong, W., Sandoval, O., et al.[2022]

In a study of 349 patients diagnosed with extensive-stage small cell lung cancer (SCLC) in British Columbia, only 36% of those receiving platinum-doublet chemotherapy were eligible for first-line immune checkpoint inhibitors (ICI), highlighting a significant gap in treatment options for the majority of patients.

After one or two cycles of chemotherapy, an additional 11% of patients improved their performance status to become eligible for ICI, suggesting that treatment strategies may need to adapt to include patients with poorer initial health status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. Rittberg, R., Leung, B., Al-Hashami, Z., et al.[2022]

Atezolizumab, an anti-PD-L1 therapy, was well tolerated in a study of 45 patients with advanced melanoma, showing that most side effects were mild (grade 1/2) and no treatment-related deaths occurred.

The treatment resulted in a 30% overall response rate and a median overall survival of 23 months, with certain biomarkers like PD-L1 expression and tumor mutational burden linked to better outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. Hamid, O., Molinero, L., Bolen, CR., et al.[2020]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

In a study of 99 previously untreated patients with extensive disease small cell lung cancer (ED-SCLC), adding atezolizumab to the standard carboplatin and etoposide regimen significantly improved overall survival, extending it to 20.8 months compared to 12.1 months for those receiving carboplatin and etoposide alone.

While there was no significant difference in progression-free survival between the two treatment groups, certain subgroups (such as older patients, males, and those with better health status) showed particularly enhanced survival benefits from the addition of atezolizumab, indicating its potential for personalized treatment approaches.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. Kubo, S., Kobayashi, N., Matsumoto, H., et al.[2023]

Atezolizumab, combined with carboplatin and etoposide, significantly improves overall survival and progression-free survival in patients with extensive-stage small cell lung cancer, based on data from the IMpower133 trial involving previously untreated patients.

The treatment regimen is generally well tolerated, with no new safety concerns identified, and it does not negatively impact patients' quality of life, making it a valuable first-line therapy option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab: A Review in Extensive-Stage SCLC. Frampton, JE.[2021]

In a study of 143 small cell lung cancer patients treated with either durvalumab or atezolizumab plus chemotherapy, durvalumab showed a significantly better median overall survival of 22.0 months compared to 10.0 months for atezolizumab (P=0.03).

The addition of radiotherapy to PD-L1 inhibitor therapy may improve long-term survival, but it also increases the risk of immune-related pneumonitis, highlighting the need for careful monitoring during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of durvalumab + chemotherapy vs. atezolizumab + chemotherapy in the treatment of small‑cell lung cancer: a retrospective comparative cohort study. Zou, Y., Ren, X., Zhang, H., et al.[2023]

Atezolizumab and durvalumab have been approved by the FDA for first-line treatment of extensive stage small cell lung cancer (SCLC) in combination with chemotherapy, showing significant improvements in overall survival (OS) compared to chemotherapy alone, with median OS of 12.3 months and 13.0 months respectively.

Both drugs demonstrated a safety profile consistent with known toxicities of immune-checkpoint inhibitors, marking a significant advancement in treatment options for SCLC, which has seen limited improvements in survival over the past 30 years.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer. Mathieu, L., Shah, S., Pai-Scherf, L., et al.[2021]

The combination of atezolizumab, a PD-L1 inhibitor, with platinum-based chemotherapy significantly improves overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone.

This research suggests that this combination therapy could become a new first-line treatment option for patients suffering from this aggressive form of lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Study: Atezolizumab Improves Survival in SCLC. [2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06287775

NCT06287775 | Testing the Combination of an Anti-cancer ... Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients ...

2. oryzon.com oryzon.com/en/news-events/news/oryzon-announces-first-patient-dosed-nci-sponsored-phase-iii-clinical-trial

ORYZON announces first patient dosed in NCI-sponsored ... The first patient has been dosed in a Phase I/II trial of iadademstat, Oryzon's potent and selective LSD1 inhibitor, in combination with immune checkpoint ...

3. clinicaltrialvanguard.com clinicaltrialvanguard.com/news/oryzon-doses-first-patient-in-iadademstat-trial-in-small-cell-lung-cancer/

Oryzon Doses First Patient in iadademstat Trial in Small ... Positive results could significantly alter the treatment landscape for SCLC and potentially pave the way for accelerated regulatory pathways.

4. oryzon.com oryzon.com/en/news-events/news/oryzon-strengthens-patent-portfolio-iadademstat-and-vafidemstat-new-decisions

ORYZON strengthens patent portfolio for iadademstat and ... Iadademstat is currently being evaluated in combination with PD-L1 inhibitors (atezolizumab or durvalumab) in first line SCLC patients with ...

5. uvahealth.com uvahealth.com/clinical-trials/trial/302115

Clinical Trials | A Phase I Dose Finding and ... In this study, you will get the study drug iadademstat in combination with either atezolizumab or durvalumab. ... small cell lung cancer when iadademstat is ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06287775?term=NCT06287775&rank=1

NCT06287775 | Testing the Combination of an Anti-cancer ... 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 ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39500124/

Real-world comparison of the efficacy and safety ... In this real-world retrospective study, durvalumab was associated with improved overall survival in patients with extensive-stage small cell lung cancer ...