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.
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
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.
Parallel
Durvalumab
Drug1500mg IV on Day 1 of every Cycle
Monalizumab
Drug1500mg IV on Day 1 of every Cycle
Carboplatin or Cisplatin
DrugOn Day 1 of Cycles 1-4 by IV: Carboplatin: AUC 5-6 OR Cisplatin: 75-80mg/m\^2
Etoposide
Drug80-100mg/m\^2 IV on Days 1-3 of Cycles 1-4
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.
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.
Objective Response Rate (ORR)
The objective response rate for the extensive stage cohort is the proportion of all subjects with confirmed PR or CR according to RECIST 1.1, from the start of treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the start of treatment)
Safety and Tolerability
Safety and tolerability for the limited stage cohort will be assessed by the grading of adverse events based on Common Toxicity Criteria for Adverse Events (CTCAE) v5.
1 Year Overall Survival (OS)
OS is defined as the time from Day 1 of treatment until death as a result of any cause.
Intracranial PFS (iPFS)
iPFS is defined as the time from Day 1 of treatment until the criteria for intracranial disease progression is met as defined by RECIST 1.1 or administration of brain radiation or death as a result of any cause, whichever comes first.
Click on the lead sponsor to view all of their trials.
Hirva Mamdani
Lead sponsor
Hoosier Cancer Research Network
Sponsor institution
AstraZeneca
Collaborator
Barbara Ann Karmanos Cancer Institute
Collaborator
