What side effects are associated with this type of intervention?

Common treatments for Small Cell Lung Cancer (SCLC), particularly those involving immune checkpoint inhibitors like Durvalumab (PD-L1 inhibitor) and investigational agents like Monalizumab (anti-NKG2A antibody), are associated with a range of side effects. Immune checkpoint inhibitors can cause immune-related adverse events (irAEs) such as pneumonitis, colitis, hepatitis, endocrinopathies, and skin reactions. These side effects can vary in severity and may require immunosuppressive therapy. When combined with chemotherapy, these treatments can also lead to increased incidences of myelosuppression, nausea, vomiting, and neuropathy.

What prior FDA approvals exist?

The FDA has approved several immune checkpoint inhibitors for the treatment of Small Cell Lung Cancer (SCLC). A notable approval is for Atezolizumab (a PD-L1 inhibitor) in combination with carboplatin and etoposide for first-line treatment of extensive-stage SCLC. This approval was based on the IMpower133 trial, which demonstrated improved overall survival and progression-free survival with the addition of Atezolizumab to chemotherapy. Another significant approval is for Durvalumab (a PD-L1 inhibitor) in combination with etoposide and either carboplatin or cisplatin for the first-line treatment of extensive-stage SCLC, as supported by the CASPIAN trial. These treatments are similar to the ongoing studies involving Durvalumab and Monalizumab, which are being investigated for their potential synergistic effects in SCLC.

What other types of research exist?

Promising alternatives to Durvalumab and Monalizumab for SCLC patients include Pembrolizumab (PD-1 inhibitor) and Nivolumab (PD-1 inhibitor), both of which have shown efficacy in various lung cancer subtypes, including those with brain metastases. Additionally, Atezolizumab (PD-L1 inhibitor) combined with chemotherapy has demonstrated benefits in non-small cell lung cancer and may be considered for SCLC. These alternatives offer potential options for patients seeking novel treatments in 2024.

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Platinum-based chemotherapy

Monalizumab + Durvalumab + Chemotherapy for Small Cell Lung Cancer (MOZART Trial)

Phase 2

Recruiting

Led By Hirva Mamdani, MD

Research Sponsored by Hirva Mamdani

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception.

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, the HCV viral load must be undetectable through PCR to be eligible for this trial. Testing is not required for screening unless mandated by local authorities. Local guidelines for testing should be followed.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up 1 year

Awards & highlights

MOZART Trial Summary

This trial involves 4 cycles of chemo, durvalumab, and monalizumab, followed by durvalumab & monalizumab maintenance, with a safety lead-in phase.

Who is the study for?

Adults with extensive stage small cell lung cancer who haven't had systemic therapy, except possibly one cycle of chemo. They must be stable if they have brain metastasis and not need steroids for a week. Participants should expect to live at least 12 weeks, have decent physical function (ECOG 0-2), and agree to use contraception. Those with certain other health conditions or treatments are excluded.Check my eligibility

What is being tested?

The trial tests a combination of the drugs durvalumab and monalizumab with platinum-based chemotherapy (carboplatin or cisplatin) plus etoposide in patients with extensive stage small cell lung cancer. After initial treatment cycles, maintenance doses continue until disease progression or unacceptable side effects occur.See study design

What are the potential side effects?

Possible side effects include reactions related to the immune system affecting various organs, infusion-related reactions, fatigue, digestive issues like diarrhea, blood disorders that can affect cells counts and increase infection risk.

MOZART Trial Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am willing to use birth control or abstain from sex.

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My hepatitis B is under control, or I've been cured of hepatitis C.

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I can take care of myself and am up and about more than half of the day.

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My lung cancer is extensive and confirmed by tests.

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I am 18 years old or older.

MOZART Trial Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ 1 year

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~1 year

This trial's timeline: 3 weeks for screening, Varies for treatment, and 1 year for reporting.

Treatment Details

Study Objectives

Outcome measures can provide a clearer picture of what you can expect from a treatment.

Primary outcome measures

1 year Progression Free Survival (PFS)

Safety and Tolerability

Secondary outcome measures

Intracranial PFS (iPFS)

Objective Response Rate (ORR)

Overall Survival (OS)

MOZART Trial Design

1Treatment groups

Experimental Treatment

Group I: Durvalumab + Monalizumab + ChemotherapyExperimental Treatment4 Interventions

On Day 1 of every Cycle for the first 4 Cycles (Cycle = 21 Days): Durvalumab 1500mg IV, Monalizumab 1500mg IV, Either Carboplatin AUC 5-6 OR Cisplatin 75-80mg/m^2 On Days 1-3 of every Cycle for the first 4 Cycles: Etoposide 80-100mg/m^2 On Day 1 of Cycles 5+ (Cycle = 28 Days): Durvalumab 1500mg IV Monalizumab 1500mg IV

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Etoposide

2010

Completed Phase 3

~2440

Durvalumab

2017

Completed Phase 2

~3870

Monalizumab

2019

Completed Phase 2

~250

Carboplatin or Cisplatin

2020

Completed Phase 2

~30

0 / 5Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The most common treatments for Small Cell Lung Cancer (SCLC) include immune checkpoint inhibitors such as PD-L1 inhibitors (e.g., Durvalumab) and anti-NKG2A antibodies (e.g., Monalizumab). PD-L1 inhibitors work by blocking the interaction between PD-L1 on tumor cells and PD-1 on T-cells, thereby preventing the tumor from evading the immune system. Monalizumab targets NKG2A, a receptor on natural killer (NK) cells and some T-cells, which inhibits their activity. By blocking NKG2A, Monalizumab enhances the immune response against cancer cells. These treatments are crucial for SCLC patients as they offer a new approach to harnessing the body's immune system to fight cancer, potentially leading to improved survival rates and better disease management.

Immunotherapy for LELC: Case Report and a Focused Review.Current status of immune checkpoint inhibitors in treatment of non-small cell lung cancer.Immunotherapy in extensive small cell lung cancer.