A Phase I Dose Finding and Phase II Randomized Trial of Iadademstat Combined With Immune Checkpoint Inhibition Maintenance After Initial Chemoimmunotherapy in Patients With Extensive-Stage Small Cell Lung Cancer

Plain English Summary

Testing the Combination of an Anti-cancer Drug, Iadademstat, With Other Anti-cancer Drugs (Atezolizumab or Durvalumab) at Improving Outcomes for Small Cell Lung Cancer is a Phase 2 clinical trial sponsored by National Cancer Institute (NCI) studying Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8. Tests the safety and effectiveness of combining Iadademstat with Atezolizumab or Durvalumab to treat extensive-stage small cell lung cancer. For patients who have already received platinum etoposide chemotherapy and either Atezolizumab or Durvalumab immunotherapy. Participation involves regular check-ups, blood tests, and possibly a CT scan. Patients will also receive IV infusions of Atezolizumab or Durvalumab. Alternative treatments include standard chemotherapy and immunotherapy. The trial aims to enroll 45 participants.

Official Summary

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 effect of the combination in treating patients with small cell lung cancer that has spread outside of the lung in which it began or to other parts of the body (extensive stage) who initially received standard of care chemotherapy and immunotherapy. Iadademstat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Immunotherapy with monoclonal antibodies, such as atezolizumab or durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Adding iadademstat to either atezolizumab or durvalumab may be able to stabilize cancer for longer than atezolizumab or durvalumab alone in treating patients with extensive stage small cell lung cancer.

Who Can Participate

Here is what you need to know about eligibility for this trial. Eligible if over 18, with extensive-stage small cell lung cancer, and previously treated with platinum etoposide and Atezolizumab or Durvalumab. Must be able to swallow pills and have certain blood test results within normal limits. Children under 18 and pregnant women are not eligible. Patients with brain metastases or other malignancies that could interfere with the study are not eligible. This trial is studying Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, so participants generally need a confirmed diagnosis. The trial is currently accepting new participants.

What They're Measuring

The primary outcome measures the time until the cancer progresses, which is crucial for patients as it can indicate how well the treatment is working. The specific primary outcome measures are: Progression free survival (From start of treatment to time of progression or death, whichever occurs first, up to 2 years). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 2, which tests whether the treatment actually works against the target condition. Phase 2 trials involve 100-300 patients and continue to monitor safety while evaluating effectiveness. This phase often tests different dosages to find the optimal amount. About 33% of Phase 2 drugs advance to Phase 3. If successful, the treatment will move to large-scale Phase 3 trials needed for FDA approval.

Why This Trial Matters

This trial aims to fill a treatment gap by potentially offering a longer-lasting response for patients with extensive-stage small cell lung cancer. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Extensive Stage Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, where improved treatment options are needed.

Investor Insight

The market for small cell lung cancer treatments is growing, with limited options, making this trial significant for investors. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if you have extensive-stage small cell lung cancer and have completed standard chemotherapy and immunotherapy. Be prepared for regular check-ups, blood tests, and possibly a CT scan. This trial is currently recruiting participants. The trial is being conducted at 20 sites. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: SEQUENTIAL
• Masking: NONE
• Enrollment: 45 participants

Interventions

• BIOLOGICAL: Atezolizumab — Given IV
• PROCEDURE: Biopsy Procedure — Undergo optional tumor biopsy
• PROCEDURE: Biospecimen Collection — Undergo blood and urine sample collection
• PROCEDURE: Computed Tomography — Undergo CT scan
• BIOLOGICAL: Durvalumab — Given IV

Primary Outcomes

• Progression free survival (From start of treatment to time of progression or death, whichever occurs first, up to 2 years)

Secondary Outcomes

• Objective response rate (Up to 2 years)
• Overall survival (Up to 2 years)
• Incidence of adverse events (Up to 30 days after last dose of study treatment)

Full Eligibility Criteria

Inclusion Criteria:

* Patients must have histologically or cytologically confirmed small cell lung cancer (SCLC)
* Patients who have been treated with platinum etoposide chemotherapy plus either atezolizumab or durvalumab immunotherapy for at least 4 cycles, and no more than 6 cycles, with either a radiographic response or stable disease. Patients are eligible if a maximum of 2 cycles of atezolizumab or durvalumab were omitted with initial treatment
* Age ≥ 18 years. Because no dosing or adverse event data are currently available on the use of iadademstat in combination with atezolizumab and durvalumab in patients \<18 years of age, children are excluded from this study
* Body weight ≥ 50 kg
* Patient is able to swallow oral medications
* Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2 (Karnofsky ≥ 60%). This assessment for eligibility will take place after patients have received 4 cycles of standard of care (SOC) chemotherapy-ICI
* Leukocytes ≥ 2,000/mcL
* Lymphocyte count ≥ 500/mcL
* Absolute neutrophil count ≥ 1,500/mcL
* Hemoglobin ≥ 9 g/dL
* Platelets ≥ 100,000/mcL
* Albumin ≥ 3 g/dL
* Total bilirubin ≤ 1.5 institutional upper limit of normal (ULN)
* Aspartate aminotransferase (AST)(serum glutamic oxaloacetic transaminase \[SGOT\])/ alanine aminotransferase (ALT) (serum glutamic pyruvic transaminase \[SGPT\]) ≤ 3 × institutional ULN unless liver metastases are present, in which case it must be ≤ 5 × ULN
* Glomerular filtration rate (GFR) ≥ 45 mL/min
* Human immunodeficiency virus (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Patients with treated brain metastases (no escalating steroid use) or asymptomatic, untreated brain metastases (≤ 5 mm without significant edema) are eligible. Brain metastases must not be new after completion of chemotherapy
* Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial
* Evidence of post-menopausal status or negative urinary or serum pregnancy test for female pre-menopausal patients. Pregnant women are excluded from this study because atezolizumab and durvalumab are monoclonal antibody agents with the potential for teratogenic or abortifacient effects. Women will be considered post-menopausal if they have been amenorrheic for 12 months without an alternative medical cause. The following age-specific requirements apply:

  * Women \< 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of exogenous hormonal treatments and if they have luteinizing hormone and follicle-stimulating hormone levels in the post-menopausal range for the institution or underwent surgical sterilization (bilateral oophorectomy or hysterectomy).
  * Women ≥ 50 years of age would be considered post-menopausal if they have been amenorrheic for 12 months or more following cessation of all exogenous hormonal treatments, had radiation-induced menopause with last menses \>1 year ago, had chemotherapy-induced menopause with last menses \> 1 year ago, or underwent surgical sterilization (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)
* The effects of iadademstat, atezolizumab, and durvalumab on the developing human fetus are unknown. For this reason and because monoclonal antibody agents are known to be teratogenic, women of child-bearing potential and males with females of child-bearing potential must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to registration, for the duration of study participation, and for 150 days after the last dose of study medication. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately.

  * Females of childbearing potential must agree to:

    * Use effective contraception during the trial and 150 days after the end of treatment.
    * Practice true abstinence during the trial and 150 days after the end of treatment.
    * Have a negative urine pregnancy test at screening.
    * Not to donate or freeze egg(s) during the course of this study or within 150 days after receiving their last dose of study drug.
  * Male patients even if surgically sterilized (i.e., status post-vasectomy) must agree to:

    * Use effective contraception during the entire study treatment period and through 150 

Trial Locations

• City of Hope Comprehensive Cancer Center, Duarte, California, United States
• City of Hope at Irvine Lennar, Irvine, California, United States
• UC San Diego Moores Cancer Center, La Jolla, California, United States
• University of California Davis Comprehensive Cancer Center, Sacramento, California, United States
• Smilow Cancer Hospital Care Center at Saint Francis, Hartford, Connecticut, United States
• Yale University, New Haven, Connecticut, United States
• Yale-New Haven Hospital North Haven Medical Center, North Haven, Connecticut, United States
• Smilow Cancer Hospital Care Center at Long Ridge, Stamford, Connecticut, United States
• Smilow Cancer Hospital Care Center-Trumbull, Trumbull, Connecticut, United States
• MedStar Georgetown University Hospital, Washington D.C., District of Columbia, United States
• ...and 10 more locations

Frequently Asked Questions

Related Conditions

• Small cell lung cancer
• Lung cancer
• Cancer immunotherapy
• Cancer chemotherapy
• Immunotherapy for cancer
• Small cell carcinoma
• Lung carcinoma
• Cancer treatment
• Cancer research
• Clinical trials for cancer

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