Monalizumab + Durvalumab + Chemotherapy for Small Cell Lung Cancer

(MOZART Trial)

Recruiting at3 trial locations

Overseen by Hirva Mamdani, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Hirva Mamdani

Must not be taking: Immunosuppressants, Live vaccines

Disqualifiers: Active infection, Autoimmune disorders, HIV, others

No Placebo Group

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

This trial tests a combination of chemotherapy and immune-boosting drugs in cancer patients who have already received some treatment. The chemotherapy attacks cancer cells directly, while the immune-boosting drugs help the body’s defense system fight the cancer.

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.

What data supports the effectiveness of the drug combination Monalizumab + Durvalumab + Chemotherapy for Small Cell Lung Cancer?

Research shows that adding durvalumab to chemotherapy with etoposide and either carboplatin or cisplatin significantly improves overall survival in patients with extensive-stage small-cell lung cancer compared to chemotherapy alone. This suggests that the combination of these drugs can be an effective treatment option. ^{1 2 3 4 5}

Is the combination of Monalizumab, Durvalumab, and Chemotherapy safe for humans?

Durvalumab combined with chemotherapy (carboplatin or cisplatin and etoposide) has been shown to have a manageable safety profile in patients with extensive-stage small-cell lung cancer, with some patients experiencing immune-related side effects. In a related study, about 25% of patients experienced immune-mediated side effects, but severe cases were less common. ^{1 2 3 4 6}

What makes the Monalizumab + Durvalumab + Chemotherapy treatment unique for small cell lung cancer?

This treatment is unique because it combines monalizumab, an innovative drug that targets the immune system, with durvalumab and chemotherapy, potentially enhancing the immune response against cancer cells in small cell lung cancer, which is not a standard approach yet. ^{1 2 3 5 7}

Research Team

Hirva Mamdani, MD

Principal Investigator

Wayne State University

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Carboplatin or Cisplatin (Platinum-based chemotherapy)
• Durvalumab (Monoclonal Antibodies)
• Etoposide (Other)
• Monalizumab (Monoclonal Antibodies)

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.

Participant Groups

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

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+

Dr. Boris C. Pasche

Barbara Ann Karmanos Cancer Institute

Chief Executive Officer since 2023

MD, PhD

Dr. Ann Schwartz

Barbara Ann Karmanos Cancer Institute

Chief Medical Officer since 2010

PhD in Epidemiology, University of Michigan

Findings from Research

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]

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, 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 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]

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]

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]

References

1. Ireland 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. [2021]

2. France pubmed.ncbi.nlm.nih.gov

Durvalumab: A Review in Extensive-Stage SCLC. [2022]

3. England 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. [2022]

4. England 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. [2021]

5. England 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. [2022]

6. Ireland 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. [2022]

7. Ireland 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. [2023]