Iadademstat + Atezolizumab/Durvalumab for Small Cell Lung Cancer
Recruiting in Palo Alto (17 mi)
+12 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1 & 2
Recruiting
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
Breakthrough Therapy
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?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.
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.
What data supports the effectiveness of the drug combination Iadademstat + Atezolizumab/Durvalumab for Small Cell Lung Cancer?
Research shows that both atezolizumab and durvalumab, when combined with chemotherapy, improve overall survival in patients with extensive-stage small cell lung cancer compared to chemotherapy alone. This suggests that these drugs can be effective components in treating this type of cancer.
12345Is the combination of Iadademstat with Atezolizumab or Durvalumab safe for humans?
Atezolizumab and Durvalumab, when combined with chemotherapy, have been generally well tolerated in patients with small cell lung cancer, with no new safety concerns beyond known side effects like rash and hypothyroidism (underactive thyroid). These treatments have been approved by the FDA based on trials showing they are safe and improve survival in this patient group.
56789What makes the drug Iadademstat + Atezolizumab/Durvalumab unique for treating small cell lung cancer?
Iadademstat, combined with atezolizumab or durvalumab, is unique because it targets specific proteins to boost the immune system's ability to fight small cell lung cancer, potentially offering a new approach compared to traditional chemotherapy.
124610Eligibility Criteria
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.
+7 more
Trial Timeline
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
Participant Groups
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.
3Treatment groups
Experimental Treatment
Active Control
Group I: Phase II, Arm I (iadademstat, atezolizumab, durvalumab)Experimental Treatment9 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 Treatment9 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 Control8 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)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
JHU Sidney Kimmel Comprehensive Cancer Center LAOBaltimore, MD
University of Virginia Cancer CenterCharlottesville, VA
University of Pittsburgh Cancer Institute (UPCI)Pittsburgh, PA
University of Kentucky/Markey Cancer CenterLexington, KY
More Trial Locations
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Who Is Running the Clinical Trial?
National Cancer Institute (NCI)Lead Sponsor
References
Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer. [2022]Small cell lung cancer (SCLC) is a rapidly progressing aggressive malignancy. Durvalumab in CASPIAN and atezolizumab in IMPower133 were found to improve overall survival (OS) for extensive-stage SCLC. Here we evaluate the proportion of real-world ES SCLC patients who may be eligible for first-line immune checkpoint inhibitor (ICI) with platinum doublet.
Clinical Activity and Safety of Atezolizumab in a Phase 1 Study of Patients With Relapsed/Refractory Small-Cell Lung Cancer. [2021]Programmed death-ligand 1 (PD-L1) protein is expressed in various cancers, including small-cell lung cancer (SCLC). Atezolizumab inhibits PD-L1 signaling, thus restoring tumor-specific T-cell immunity. Here, we report results from the first-in-human phase 1 PCD4989g study (NCT01375842) of atezolizumab, in a cohort of patients with relapsed/refractory SCLC.
Atezolizumab addition to platinum doublet: evaluating survival outcomes for patients with extensive disease small cell lung cancer. [2023]The efficacy of adding atezolizumab to the platinum doublet regimen for extensive disease small cell lung cancer (ED-SCLC) remains marginally limited.
Study: Atezolizumab Improves Survival in SCLC. [2019]Combining the PD-L1 inhibitor atezolizumab with platinum-based chemotherapy improves overall survival among patients with extensive-stage small cell lung cancer relative to chemotherapy alone. These findings could lead to a new first-line treatment option for patients with the disease.
Efficacy and safety of durvalumab + chemotherapy vs. atezolizumab + chemotherapy in the treatment of small‑cell lung cancer: a retrospective comparative cohort study. [2023]Durvalumab and atezolizumab have recently been approved in extensive small cell lung cancer (SCLC) with moderate median overall survival (OS) improvements. However, only limited data exist regarding the impact of immunotherapy in real-world SCLC patients. This study sought to assess the efficacy and safety of atezolizumab plus chemotherapy and durvalumab plus chemotherapy in the treatment of SCLC in a real-world setting.
Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. [2022]Atezolizumab is a humanised antiprogrammed death-ligand 1 (PD-L1) monoclonal antibody that inhibits PD-L1 and programmed death-1 (PD-1) and PD-L1 and B7-1 interactions, reinvigorating anticancer immunity. We assessed its efficacy and safety versus docetaxel in previously treated patients with non-small-cell lung cancer.
Safety, Clinical Activity, and Biological Correlates of Response in Patients with Metastatic Melanoma: Results from a Phase I Trial of Atezolizumab. [2020]Atezolizumab [anti-programmed death-ligand 1 (PD-L1)] selectively targets PD-L1 to block its interaction with receptors programmed death 1 and B7.1, thereby reinvigorating antitumor T-cell activity. We evaluated the long-term safety and activity of atezolizumab, along with biological correlates of clinical activity endpoints, in a cohort of patients with melanoma in an ongoing phase Ia study (NCT01375842).
Atezolizumab: A Review in Extensive-Stage SCLC. [2021]Atezolizumab (Tecentriq®), a fully humanized, monoclonal anti-programmed cell death ligand-1 (PD-L1) antibody, is the first immune checkpoint inhibitor to be approved, in combination with carboplatin and etoposide, for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Approval was based on primary data from the multinational phase I/III IMpower133 trial in PD-L1-unselected patients with previously untreated ES-SCLC. In this trial, induction therapy with atezolizumab plus carboplatin and etoposide followed by maintenance therapy with atezolizumab alone significantly prolonged overall survival (OS) and progression-free survival (PFS) compared with carboplatin and etoposide alone. The addition of atezolizumab to chemotherapy was generally well tolerated, with no new safety signals being identified beyond those previously reported for the individual agents. The most common grade 3-4 treatment-related adverse events with this regimen were haematological; the most common immune-related adverse events included rash and hypothyroidism. Importantly, the addition of atezolizumab to chemotherapy improved survival outcomes without adversely impacting patient-reported health-related quality of life (HRQOL). Thus, atezolizumab in combination with carboplatin plus etoposide has emerged as a valuable option for the first-line treatment of ES-SCLC and is being accepted as a standard of care in this setting.
FDA Approval Summary: Atezolizumab and Durvalumab in Combination with Platinum-Based Chemotherapy in Extensive Stage Small Cell Lung Cancer. [2021]The U.S. Food and Drug Administration (FDA) granted approval to atezolizumab and durvalumab in March of 2019 and 2020, respectively, for use in combination with chemotherapy for first-line treatment of patients with extensive stage small cell lung cancer. These approvals were based on data from two randomized controlled trials, IMpower133 (atezolizumab) and CASPIAN (durvalumab). Both trials demonstrated an improvement in overall survival (OS) with anti-programmed death ligand 1 antibodies when added to platinum-based chemotherapy as compared with chemotherapy alone. In IMpower133, patients receiving atezolizumab with etoposide and carboplatin demonstrated improved OS (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.54-0.91; p = .0069), with median OS of 12.3 months compared with 10.3 months in patients receiving etoposide and carboplatin. In CASPIAN, patients receiving durvalumab with etoposide and either cisplatin or carboplatin also demonstrated improved OS (HR, 0.73; 95% CI, 0.59-0.91; p = .0047) with median OS of 13.0 months compared with 10.3 months in patients receiving etoposide and either cisplatin or carboplatin. The safety profiles of both drugs were generally consistent with known toxicities of immune-checkpoint inhibitor therapies. This review summarizes the FDA perspective and data supporting the approval of these two agents. IMPLICATIONS FOR PRACTICE: Effective therapeutic options for small cell lung cancer (SCLC) are limited, and there has been modest improvement in the overall survival (OS) of patients with SCLC over the past 3 decades. The approvals of atezolizumab and of durvalumab in combination with chemotherapy for first-line treatment of patients with extensive stage SCLC represent the first approved therapies with OS benefit for this patient population since the approval of etoposide in combination with other approved chemotherapeutic agents. Additionally, the efficacy results from IMpower133 and CASPIAN lay the groundwork for possible further evaluation in other treatment settings in this disease.
Cost-Effectiveness Analysis of Atezolizumab Versus Durvalumab as First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer in the USA. [2022]Durvalumab and atezolizumab are approved as first-line therapy in extensive-stage small-cell lung cancer. Although cost-effectiveness analyses compared these immunotherapy drugs with standard chemotherapy-alone regimens, no head-to-head cost-effectiveness comparisons for these treatments exist. The aim of the present analysis is to determine the cost-effectiveness of durvalumab and atezolizumab as first-line therapy for extensive-stage small-cell lung cancer from the US payers' perspective.