Monalizumab + Durvalumab + Chemotherapy for Small Cell Lung Cancer

(MOZART Trial)

Recruiting at 3 trial locations

Overseen By Hirva Mamdani, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hirva Mamdani

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Active infection, Autoimmune disorders, HIV, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 12 weeks

38 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a combination of drugs, including monalizumab (an experimental treatment), durvalumab (an immunotherapy drug), and chemotherapy, can effectively treat small cell lung cancer. The focus is on patients with advanced lung cancer that cannot be treated with radiation alone. Researchers seek to discover if this drug combination can slow the disease or improve outcomes. It is suitable for those diagnosed with small cell lung cancer who have not received prior systemic treatment, except possibly one cycle of chemotherapy. As a Phase 2 trial, the research measures the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, you should not use immunosuppressive medication within 7 days before starting the trial drugs, except for certain types of steroids. It's best to discuss your current medications with the study team.

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

Research has shown that combining monalizumab with durvalumab is generally well-tolerated. Although specific data on this combination is still being gathered, studies suggest that durvalumab, when used with other treatments, can reduce cancer growth and help patients live longer, indicating a positive safety profile for durvalumab.

Monalizumab boosts the body's natural killer (NK) cells to fight cancer, and earlier studies have shown promising results. This suggests it could be a safe treatment, especially when used with durvalumab. However, like any treatment, side effects can occur, so safety is closely monitored in clinical trials.

Carboplatin, cisplatin, and etoposide are standard chemotherapy drugs with well-known side effects, as they have been used in cancer treatments for many years. Overall, while some side effects may occur, researchers are studying the combination of these treatments for its potential benefits and manageable safety profile. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining Monalizumab with Durvalumab and chemotherapy for small cell lung cancer because this approach introduces a novel mechanism of action. Unlike standard treatments such as chemotherapy alone, Monalizumab targets the immune checkpoints, potentially enhancing the body’s immune response against cancer cells. Durvalumab, an immunotherapy, is also included to block the PD-L1 pathway, which can further boost the immune system's ability to fight the cancer. Together with chemotherapy drugs like Carboplatin or Cisplatin and Etoposide, this combination aims to improve effectiveness by attacking the cancer from multiple angles, offering hope for better outcomes.

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

In this trial, participants will receive a combination of monalizumab and durvalumab with chemotherapy to help the immune system fight small cell lung cancer (SCLC). Research has shown that durvalumab reduces the risk of cancer spreading and helps patients live longer after chemotherapy. Studies have also examined monalizumab and found it may enhance other cancer treatments by boosting the immune system. Early results suggest that this combination could benefit patients with extensive-stage SCLC. Although still under study, this combination therapy has the potential to improve outcomes for this challenging type of cancer. ^{6 7 8 9 10}

Who Is on the Research Team?

Hirva Mamdani, MD

Principal Investigator

Wayne State University

Are You a Good Fit for This Trial?

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.

Inclusion Criteria

Written informed consent and HIPAA authorization for release of personal health information prior to registration. Note: HIPAA authorization may be included in the informed consent or obtained separately.

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

You have a medical condition that can be measured using specific guidelines.

Exclusion Criteria

I have had or will have chest radiation before systemic therapy or as consolidation.

You have had or currently have another type of cancer that could affect the evaluation of the new treatment.

I do not have any serious ongoing illnesses that could interfere with the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Lead-in

Safety lead-in phase to confirm the safety of the proposed dose of monalizumab in combination with chemotherapy and durvalumab

3-4 weeks

Treatment

Participants receive a platinum drug, etoposide, durvalumab, and monalizumab every 3 weeks for 4 cycles

12 weeks

4 visits (in-person)

Maintenance Treatment

Participants continue maintenance treatment with durvalumab and monalizumab every 4 weeks until disease progression or other criteria

Until disease progression or other criteria

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

What Are the Treatments Tested in This Trial?

Interventions

• Carboplatin or Cisplatin
• Durvalumab
• Etoposide
• Monalizumab

Trial Overview 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.

How Is the Trial Designed?

Group I: Durvalumab + Monalizumab + Chemotherapy Experimental Treatment 4 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

Carboplatin or Cisplatin is already approved in European Union, United States for the following indications:

Approved in European Union as Cisplatin for:

• Testicular cancer
• Ovarian cancer
• Lung cancer
• Bladder cancer
• Cervical cancer

Approved in United States as Cisplatin for:

• Metastatic testicular tumors
• Metastatic ovarian tumors
• Advanced bladder cancer

Approved in European Union as Carboplatin for:

• Ovarian carcinoma
• Small cell lung cancer

Approved in United States as Carboplatin for:

• Initial treatment of advanced ovarian carcinoma
• Palliative treatment of recurrent ovarian carcinoma
• Small cell lung cancer

Who Is Running the Clinical Trial?

Hirva Mamdani

Lead Sponsor

Trials

1

Recruited

40+

AstraZeneca

Industry Sponsor

Trials

4,491

Recruited

290,540,000+

Sir Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Dr. Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Pascal Soriot

AstraZeneca

Chief Executive Officer since 2012

Veterinary Medicine from École nationale vétérinaire d'Alfort, MBA from HEC Paris

Cristian Massacesi

AstraZeneca

Chief Medical Officer since 2021

MD from Marche Polytechnic University, Medical Oncology training at Royal Marsden Hospital, Kaplan Comprehensive Cancer Center, and European Institute of Oncology

Barbara Ann Karmanos Cancer Institute

Collaborator

Trials

166

Recruited

9,300+

Published Research Related to This Trial

In a study of 518 patients with extensive small cell lung cancer (SCLC) receiving atezolizumab plus chemotherapy, the median overall survival was 11.3 months, with 46.7% of patients alive at 12 months, indicating the treatment's effectiveness in a real-world setting.

The study demonstrated that 23.6% of patients continued atezolizumab treatment beyond disease progression, suggesting a potential strategy for improving outcomes, particularly in patients with better performance status (PS 0/1) who had a median overall survival of 12.2 months.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. Falchero, L., Guisier, F., Darrason, M., et al.[2023]

In the CASPIAN study involving 805 patients with extensive-stage small-cell lung cancer (ES-SCLC), the combination of durvalumab and platinum-etoposide significantly improved overall survival compared to platinum-etoposide alone, with a median survival of 12.9 months versus 10.5 months.

However, adding tremelimumab to durvalumab and platinum-etoposide did not provide a significant survival benefit, indicating that durvalumab plus platinum-etoposide should be considered the new standard of care for first-line treatment of ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Goldman, JW., Dvorkin, M., Chen, Y., et al.[2021]

In the phase III CASPIAN study, durvalumab combined with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer, with a median overall survival of 12.9 months compared to 10.5 months for the control group.

After more than 3 years of follow-up, durvalumab plus etoposide showed a 36-month overall survival rate of 17.6%, indicating that this combination is a promising first-line treatment option for extensive-stage small-cell lung cancer.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab, with or without tremelimumab, plus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer: 3-year overall survival update from CASPIAN. Paz-Ares, L., Chen, Y., Reinmuth, N., et al.[2022]

In the phase III CASPIAN trial involving previously untreated adults with extensive-stage small cell lung cancer (ES-SCLC), the addition of durvalumab to chemotherapy significantly improved overall survival and progression-free survival compared to chemotherapy alone.

Durvalumab combined with etoposide and either carboplatin or cisplatin demonstrated a manageable safety profile, making it a valuable first-line treatment option and an accepted standard of care for patients with ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. Al-Salama, ZT.[2022]

In the phase III CASPIAN study, the combination of durvalumab with etoposide and either cisplatin or carboplatin significantly improved overall survival in patients with extensive-stage small-cell lung cancer compared to etoposide plus platinum alone.

Patient-reported outcomes showed that the addition of durvalumab not only maintained quality of life but also delayed the worsening of key symptoms like appetite loss, cough, and fatigue, indicating a beneficial impact on patients' overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-reported outcomes with first-line durvalumab plus platinum-etoposide versus platinum-etoposide in extensive-stage small-cell lung cancer (CASPIAN): a randomized, controlled, open-label, phase III study. Goldman, JW., Garassino, MC., Chen, Y., et al.[2021]

This study is investigating the combination of the anti-PD-L1 antibody durvalumab with carboplatin and etoposide in 56 previously untreated patients with extensive-stage small-cell lung cancer (ES-SCLC) and poor performance status (PS 2-3), aiming to assess its safety and efficacy.

The primary goal is to evaluate the tolerability of this treatment regimen, while secondary outcomes include survival rates and response to treatment, addressing a significant unmet medical need for patients with poor prognosis in ES-SCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase II study of carboplatin and etoposide plus durvalumab for previously untreated extensive-stage small-cell lung cancer (ES-SCLC) patients with a poor performance status (PS): NEJ045A study protocol. Asao, T., Watanabe, S., Tanaka, T., et al.[2022]

In the phase III PACIFIC trial, durvalumab treatment led to a low incidence of immune-mediated adverse events (imAEs), with any-grade immune-mediated pneumonitis occurring in 9.4% of patients and grade 3/4 imAEs in only 3.4%.

Despite the occurrence of imAEs being more common with durvalumab compared to placebo, these events were generally manageable with treatments like corticosteroids, indicating that the benefits of the PACIFIC regimen outweigh the risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Characterizing immune-mediated adverse events with durvalumab in patients with unresectable stage III NSCLC: A post-hoc analysis of the PACIFIC trial. Naidoo, J., Vansteenkiste, JF., Faivre-Finn, C., et al.[2022]

Citations

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A phase II trial of monalizumab in combination with ... Pre-clinical data have demonstrated that the absence of NK cells substantially enhances metastatic dissemination of SCLC tumor cells in vivo. NK ...

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NCT05221840 | A Global Study to Assess the Effects of ... This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination ...