A Phase II Trial of MOnaliZumab in Combination With durvAlumab (MEDI4736) for tReatmenT of Small Cell Lung Cancer (MOZART)

Plain English Summary

MOnaliZumab in Combination With durvAlumab (MEDI4736) for tRreatmenT of Small Cell Lung Cancer is a Phase 2 clinical trial sponsored by Hirva Mamdani studying Small Cell Lung Cancer, SCLC, Extensive Stage Small Cell Lung Cancer, Limited Stage Small-Cell Lung Cancer. This trial tests a combination of drugs (monalizumab, durvalumab, and chemotherapy) to treat small cell lung cancer. It is for patients with either extensive-stage or limited-stage small cell lung cancer. Participation involves receiving chemotherapy and immunotherapy infusions, with specific treatment plans depending on the stage of cancer. Alternative treatments may include standard chemotherapy, radiation, or other immunotherapy combinations. The trial aims to enroll 84 participants.

Official Summary

This study has 2 cohorts: MOZART-ES cohort (for extensive-stage SCLC) and MOZART-LS cohort (for limited-stage SCLC). MOZART-ES cohort: Study treatment will consist of a platinum drug (carboplatin or cisplatin per investigator's choice) plus etoposide plus durvalumab plus monalizumab every 3 weeks for 4 cycles. After 4 cycles, subjects will continue maintenance treatment with durvalumab plus monalizumab every 4 weeks until disease progression, unacceptable toxicity, decision to stop study treatment, or withdrawal of consent. Patients who have received one prior cycle of treatment before enrolling on the study will receive a total of 4 cycles with monalizumab, durvalumab, and chemotherapy. There will be a safety lead-in phase, including 6 to 12 patients, to confirm the safety of the proposed dose of monalizumab to use in combination with chemotherapy and durvalumab. MOZART-LS cohort: Study treatment will consist of durvalumab and monalizumab following standard of care chemo-radiation consisting of a platinum drug (carboplatin or cisplatin per investigator's choice) plus etoposide for 3-4 cycles and standard dose radiation. Radiation therapy should have started before completion of cycle 2 of chemotherapy. NOTE: Subjects who have non-progressive disease and meet the eligibility criteria can start study treatment up to 56 days from completion of chemo-radiation. Durvalumab and monalizumab will be administered every 4 weeks for up to 2 years (26 cycles), disease progression, unacceptable toxicity, decision to stop study treatment, or withdrawal consent, whichever occurs first.

Who Can Participate

Here is what you need to know about eligibility for this trial. Patients with newly diagnosed extensive-stage small cell lung cancer who have not received prior systemic therapy (except for up to one cycle of chemotherapy with or without durvalumab). Patients with limited-stage small cell lung cancer who have completed chemoradiation and have not experienced disease progression. Must be 18 years or older with adequate organ function and a life expectancy of at least 12 weeks. Cannot have active infections, known allergies to study drugs, recent major surgery, or active autoimmune disorders. This trial is studying Small Cell Lung Cancer, SCLC, Extensive Stage Small Cell Lung Cancer, Limited Stage Small-Cell Lung Cancer, so participants generally need a confirmed diagnosis.

What They're Measuring

The primary outcome measures, such as 1-year Progression-Free Survival and safety, will indicate how well the combination treatment controls the cancer and how tolerable it is for patients. The specific primary outcome measures are: 1 year Progression Free Survival (PFS) (1 year); Safety and Tolerability (24 Months). 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 investigating a novel combination therapy for small cell lung cancer, a disease with limited effective treatment options. Phase 2 success would typically lead to larger Phase 3 trials needed for regulatory approval. This research targets Small Cell Lung Cancer, SCLC, Extensive Stage Small Cell Lung Cancer, Limited Stage Small-Cell Lung Cancer, where improved treatment options are needed.

Investor Insight

This trial explores a combination of immunotherapies, a growing area in oncology, suggesting potential for future treatments in a market with significant unmet needs. Phase 2 trials have approximately a 15-20% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor about the specific chemotherapy drugs used, the duration of treatment, and potential side effects. Be prepared for regular clinic visits for infusions and monitoring, which may involve blood tests and scans. Understand that the trial is currently suspended, so enrollment may not be possible at this time. The trial is being conducted at 4 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: NON_RANDOMIZED
• Model: PARALLEL
• Masking: NONE
• Enrollment: 84 participants

Interventions

• DRUG: Durvalumab — 1500mg IV on Day 1 of every Cycle
• DRUG: Monalizumab — 1500mg IV on Day 1 of every Cycle
• DRUG: Carboplatin or Cisplatin — On Day 1 of Cycles 1-4 by IV: Carboplatin: AUC 5-6 OR Cisplatin: 75-80mg/m\^2
• DRUG: Etoposide — 80-100mg/m\^2 IV on Days 1-3 of Cycles 1-4

Primary Outcomes

• 1 year Progression Free Survival (PFS) (1 year)
• Safety and Tolerability (24 Months)

Secondary Outcomes

• Objective Response Rate (ORR) (24 Months)
• Safety and Tolerability (24 Months)
• 1 Year Overall Survival (OS) (24 Months)
• Intracranial PFS (iPFS) (24 Months)

Full Eligibility Criteria

General Inclusion Criteria:

1. 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.
2. Age ≥ 18 years at the time of consent.
3. Demonstrate adequate organ function. All screening labs to be obtained within 28 days prior to registration.

   * Absolute Neutrophil Count (ANC) \> 1500mm\^3
   * Hemoglobin ≥ 9 g/dL
   * Platelet Count (PLT) ≥ 100,000 per mm3
   * Calculated creatinine clearance ≥ 40 mL/min
   * Bilirubin ≤ 1.5 × upper limit of normal (ULN); subjects with confirmed Gilbert's syndrome (persistent or recurrent hyperbilirubinemia that is predominantly unconjugated in the absence of hemolysis or hepatic pathology), may be allowed with sponsor-investigator approval.
   * Apsartate aminotransferase (AST) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
   * Alanine aminotransferase (ALT) ≤ 2.5 x institutional upper limit of normal unless liver metastases are present, in which case it must be ≤5x ULN
4. Females of childbearing potential must have a negative serum pregnancy test at screening.
5. Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception.
6. Life expectancy of ≥ 12 weeks.
7. 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.

Extensive Stage Specific Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of small cell lung cancer:

   \- Extensive disease (American Joint Committee on Cancer Stage (8th edition) IV SCLC \[T any, N any, M1 a/b\]), OR T3-4 disease due to multiple lung nodules that are too extensive or have tumor/nodal volume that is too large to be encompassed in a tolerable radiation plan.
2. No prior systemic therapy for small-cell lung cancer, with the following exceptions: Up to one cycle of platinum doublet chemotherapy with or without durvalumab is allowed up to 4 weeks prior to registration on this study. Patients with irreversible toxicity not reasonably expected to be exacerbated by treatment with durvalumab and monalizumab may be included only after consultation with the sponsor-investigator. Patients should not have received Trilaciclib.
3. Measurable disease according to RECIST v1.1.
4. Subjects with treated brain metastasis or untreated asymptomatic brain metastasis that is clinically stable per investigator discretion and not requiring systemic steroids for ≥ 7 days. NOTE: Prophylactic cranial radiation (PCI) is allowed per investigator's discretion.
5. ECOG Performance Status of 0-2.

Limited Stage Specific Inclusion Criteria:

1. Histologically or cytologically confirmed diagnosis of small cell lung cancer:

   \- Limited-stage disease (American Joint Committee on Cancer Stage (8th edition) I-III SCLC \[T any, N any, M0\])
2. Has received platinum (cis- or carboplatin) and etoposide chemotherapy (4 cycles preferred; 3 cycles allowed if disease control is achieved and no additional benefit is expected with an additional cycle of chemotherapy in the opinion of the investigator) administered concurrently with radiation (60-66Gy daily or 45Gy BID). Radiation should have started no later than end of cycle 2 of chemotherapy.
3. Non-progressive disease following completion of chemo-radiation.
4. No evidence of brain metastasis. NOTE: PCI is allowed per investigator's discretion.
5. Ability to start study treatment within 56 days of completing chemo-radiation, counting from whichever ends later
6. ECOG Performance Status of 0-1.

Exclusion Criteria:

1. Body weight ≤ 40 kg.
2. Active infection requiring intravenous antibiotic therapy.
3. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
4. Major surgical procedure (as defined by the investigator) within 28 days prior to the first dose of study treatment. NOTE: Local surgery of isolated lesions for palliative intent is acceptable.
5. History of active primary immunodeficiency.
6. Known to have tested positive for human immunodeficiency virus (HIV) (positive HIV 1/2 antibodies) or active tuberculosis infection (clinical evaluation that may include clinical history, physical examination and radiographic findings, or tuberculosis testing in line with local practice).
7. Presence of neurologic paraneoplastic syndrome.
8. Active or prior documented autoimmune or inflammatory disorders (inc

Trial Locations

• Indiana University Melvin and Bren Simon Comprehensive Cancer Center, Indianapolis, Indiana, United States
• University of Iowa Hospitals and Clinics, Iowa City, Iowa, United States
• Karmanos Cancer Center (Wayne State University), Detroit, Michigan, United States
• University of Virginia Health System, Charlottesville, Virginia, United States

Frequently Asked Questions

Related Conditions

• Small Cell Lung Cancer
• Lung Cancer
• Extensive Stage Small Cell Lung Cancer
• Limited Stage Small-Cell Lung Cancer
• Chemotherapy
• Immunotherapy
• Oncology
• Cancer Treatment
• Thoracic Oncology
• Non-Small Cell Lung Cancer

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