MOnaliZumab in Combination With durvAlumab (MEDI4736) for tRreatmenT of Small Cell Lung Cancer

NCT05903092 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: HCRN LUN21-530
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 4

Brief 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.

Conditions

SCLC; Extensive Stage Small Cell Lung Cancer; Small Cell Lung Cancer; Limited Stage Small-Cell Lung Cancer

Keywords

Small cell lung cancer; First-line therapy; Chemoimmunotherapy; Immunotherapy; Monalizumab

Outcome Measures

Primary Outcomes (2)

• 1 year Progression Free Survival (PFS)

  PFS is defined as the time from Day 1 of treatment until the criteria for disease progression is met as defined by RECIST 1.1 or death as a result of any cause.

  1 year

• Safety and Tolerability

  Safety and tolerability for the extensive stage cohort will be assessed by the grading of adverse events based on Common Toxicity Criteria for Adverse Events (CTCAE) v5.

  24 Months

Secondary Outcomes (4)

• Objective Response Rate (ORR)

  24 Months

• Safety and Tolerability

  24 Months

• 1 Year Overall Survival (OS)

  24 Months

• Intracranial PFS (iPFS)

  24 Months

Study Arms (2)

Extensive Stage Cohort

EXPERIMENTAL

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

Drug: Durvalumab; Drug: Monalizumab; Drug: Carboplatin or Cisplatin; Drug: Etoposide

Limited Stage Cohort

EXPERIMENTAL

On Day 1 of every Cycle: Durvalumab 1500mg IV, Monalizumab 1500mg IV will be administered, for up to 26 Cycles (Cycle = 28 days).

Drug: Durvalumab; Drug: Monalizumab

Interventions

Monalizumab DRUG

1500mg IV on Day 1 of every Cycle

Extensive Stage Cohort; Limited Stage Cohort

Carboplatin or Cisplatin DRUG

On Day 1 of Cycles 1-4 by IV: Carboplatin: AUC 5-6 OR Cisplatin: 75-80mg/m\^2

Extensive Stage Cohort

Durvalumab DRUG

1500mg IV on Day 1 of every Cycle

Also known as: Imfinzi

Extensive Stage Cohort; Limited Stage Cohort

Etoposide DRUG

80-100mg/m\^2 IV on Days 1-3 of Cycles 1-4

Also known as: VP-16

Extensive Stage Cohort

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• Age ≥ 18 years at the time of consent.
• 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
• Females of childbearing potential must have a negative serum pregnancy test at screening.
• Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception.
• Life expectancy of ≥ 12 weeks.
• 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.
• Histologically or cytologically confirmed diagnosis of small cell lung cancer:

You may not qualify if:

• Body weight ≤ 40 kg.
• Active infection requiring intravenous antibiotic therapy.
• Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
• 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.
• History of active primary immunodeficiency.
• 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).
• Presence of neurologic paraneoplastic syndrome.
• Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease \[e.g., ulcerative colitis or Crohn's disease\], systemic lupus erythematosus, sarcoidosis, Wegener syndrome \[granulomatosis with polyangiitis\], rheumatoid arthritis, hypophysitis, uveitis, etc). The following are exceptions to this criterion:
• Patients with vitiligo or alopecia
• Patients with hypothyroidism (e.g., following Hashimoto syndrome) stable on hormone replacement
• Any chronic skin condition that does not require systemic therapy
• Patients without active disease in the last 2 years may be included but only after consultation with the study physician
• Patients with celiac disease controlled by diet alone
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study treatment. NOTE: Subjects, if enrolled, should not receive live vaccine whilst receiving study treatment and up to 30 days after the last dose of study treatment.
• Uncontrolled intercurrent illness, including but not limited to, ongoing or active infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable angina pectoris, cardiac arrhythmia, interstitial lung disease, serious chronic gastrointestinal conditions associated with diarrhea, or psychiatric illness/social situations that would limit compliance with study requirement, substantially increase risk of incurring AEs or compromise the ability of the patient to give written informed consent.

Sponsors & Collaborators

• AstraZeneca: collaborator
• Hirva Mamdani: lead
• Barbara Ann Karmanos Cancer Institute: collaborator

Study Sites (4)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202, United States

RECRUITING

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242, United States

RECRUITING

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, 48201, United States

RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Small Cell Lung Carcinoma

Interventions

durvalumab; monalizumab; Carboplatin; Cisplatin; Etoposide

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Podophyllotoxin; Tetrahydronaphthalenes; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Glucosides; Glycosides; Carbohydrates

Study Officials

• Hirva Mamdani, MD

  Wayne State University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hirva Mamdani, MD

CONTACT

313-576-8711; mamdanih@karmanos.org

Allison Lipps

CONTACT

317-634-5842; alipps@hoosiercancer.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: June 5, 2023
• First Posted: June 15, 2023
• Study Start: September 26, 2023
• Primary Completion (Estimated): October 31, 2029
• Study Completion (Estimated): October 31, 2030
• Last Updated: April 29, 2026

Record last verified: 2026-04

Locations

US (4)