SUSPENDED

MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer

Conditions

Small Cell Lung Cancer SCLC Extensive Stage Small Cell Lung Cancer First-line therapy Chemoimmunotherapy Immunotherapy Monalizumab

Quick Navigation

Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

The 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.

Official Title

A Phase II Trial of MOnaliZumab in Combination With durvAlumab (MEDI4736) Plus Platinum-based chemotheRapy for First-line Treatment of Extensive Stage Small Cell Lung Cancer (MOZART)

Quick Facts

Study Start:2023-09-26

Study Completion:2028-01-03

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:SUSPENDED

Study ID

NCT05903092

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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. ECOG Performance Status of 0-2. 4. 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. 5. No prior systemic therapy for small-cell lung cancer, with the following exceptions: 6. Measurable disease according to RECIST v1.1 7. Subjects with treated brain metastasis and those with untreated asymptomatic brain metastasis are eligible if they are clinically stable per investigator discretion and not requiring systemic steroids for ≥ 7 days. Prophylactic cranial radiation (PCI) is allowed per investigator's discretion. 8. 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 9. Females of childbearing potential must have a negative serum pregnancy test at screening. 10. Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception. 11. Life expectancy of ≥ 12 weeks. 12. 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.	1. Body weight ≤ 40 kg. 2. Receipt of radiotherapy to the chest within 6 months prior to initiating systemic therapy or planned consolidation chest radiation therapy. NOTE: Radiation therapy outside of the chest for palliative care (e.g., bone metastasis) is allowed but must be completed before the first dose of the study medication. 3. Active infection requiring intravenous antibiotic therapy. 4. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients. 5. 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. 6. History of active primary immunodeficiency. 7. 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). 8. Presence of neurologic paraneoplastic syndrome. 9. 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 10. Current or prior use of immunosuppressive medication within 7 days before the first dose of monalizumab and 'on-study' durvalumab. The following are exceptions to this criterion: * Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection) * Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent * Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication), and for prevention of chemotherapy induced nausea/vomiting per institutional standards. 11. 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. 12. 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. 13. Patients who have received prior one dose of durvalumab along with chemotherapy: * Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy. * Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic. * Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day. 14. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study). 15. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per investigator discretion. 16. History of leptomeningeal carcinomatosis. 17. History of allogeneic organ transplantation. 18. Treatment with any investigational drug within 28 days prior to registration or concurrent enrolment in another clinical study, unless observational in nature.

Inclusion Criteria

Exclusion 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. ECOG Performance Status of 0-2.
4. 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.
5. No prior systemic therapy for small-cell lung cancer, with the following exceptions:
6. Measurable disease according to RECIST v1.1
7. Subjects with treated brain metastasis and those with untreated asymptomatic brain metastasis are eligible if they are clinically stable per investigator discretion and not requiring systemic steroids for ≥ 7 days. Prophylactic cranial radiation (PCI) is allowed per investigator's discretion.
8. 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
9. Females of childbearing potential must have a negative serum pregnancy test at screening.
10. Females of childbearing potential and male subjects must be willing to abstain from heterosexual intercourse or to use an effective method(s) of contraception.
11. Life expectancy of ≥ 12 weeks.
12. 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.

1. Body weight ≤ 40 kg.
2. Receipt of radiotherapy to the chest within 6 months prior to initiating systemic therapy or planned consolidation chest radiation therapy. NOTE: Radiation therapy outside of the chest for palliative care (e.g., bone metastasis) is allowed but must be completed before the first dose of the study medication.
3. Active infection requiring intravenous antibiotic therapy.
4. Known allergy or hypersensitivity to any of the study drugs or any of the study drug excipients.
5. 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.
6. History of active primary immunodeficiency.
7. 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).
8. Presence of neurologic paraneoplastic syndrome.
9. 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
10. Current or prior use of immunosuppressive medication within 7 days before the first dose of monalizumab and 'on-study' durvalumab. The following are exceptions to this criterion:
* Intranasal, inhaled, topical steroids, or local steroid injections (e.g., intra articular injection)
* Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent
* Steroids as premedication for hypersensitivity reactions (e.g., CT scan premedication), and for prevention of chemotherapy induced nausea/vomiting per institutional standards.
11. 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.
12. 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.
13. Patients who have received prior one dose of durvalumab along with chemotherapy:
* Must not have experienced a toxicity that led to permanent discontinuation of prior immunotherapy.
* Must not have experienced a ≥Grade 3 immune related AE or an immune related neurologic or ocular AE of any grade while receiving prior immunotherapy. NOTE: Patients with endocrine AE of ≤ Grade 2 are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic.
* Must not have required the use of additional immunosuppression other than corticosteroids for the management of an AE and not currently require maintenance doses of \> 10 mg prednisone or equivalent per day.
14. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
15. Patients with a prior or concurrent malignancy whose natural history or treatment has the potential to interfere with the safety or efficacy assessment of the investigational regimen, per investigator discretion.
16. History of leptomeningeal carcinomatosis.
17. History of allogeneic organ transplantation.
18. Treatment with any investigational drug within 28 days prior to registration or concurrent enrolment in another clinical study, unless observational in nature.

Contacts and Locations

Principal Investigator

Hirva Mamdani, MD

PRINCIPAL_INVESTIGATOR

Wayne State University

Study Locations (Sites)

Indiana University Melvin and Bren Simon Comprehensive Cancer Center

Indianapolis, Indiana, 46202

United States

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52242

United States

Karmanos Cancer Center (Wayne State University)

Detroit, Michigan, 48201

United States

University of Virginia Health System

Charlottesville, Virginia, 22908

United States

Collaborators and Investigators

Sponsor: Hirva Mamdani

Hirva Mamdani, MD, PRINCIPAL_INVESTIGATOR, Wayne State University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-09-26

Study Completion Date2028-01-03

Study Record Updates

Study Start Date2023-09-26

Study Completion Date2028-01-03

Terms related to this study

Keywords Provided by Researchers

Small cell lung cancer
First-line therapy
Chemoimmunotherapy
Immunotherapy
Monalizumab

Additional Relevant MeSH Terms

Small Cell Lung Cancer
SCLC
Extensive Stage Small Cell Lung Cancer