This phase II trial tests how well biomarker tests on patients tumor tissue works in selecting personalized treatments for patients with extensive stage small cell lung cancer (ES-SCLC). Biomarker tests look for certain features in cancer cells that may give doctors more information about what is driving cancer and how to treat it. Based on the biomarker test results, study doctors can determine the subtype of ES-SCLC that study treatments can target. This study also tests different types of maintenance treatment for ES-SCLC with drugs durvalumab, saruparib, ceralasertib or monalizumab. Maintenance treatment is given after initial treatment and is given to help keep the cancer under control and prevent it from getting worse. Immunotherapy with monoclonal antibodies, such as durvalumab and monalizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Saruparib is a PARP inhibitor. PARP is a protein that helps repair damaged deoxyribonucleic acid (DNA). Blocking PARP may prevent cancer cells from repairing their damaged DNA, causing them to die. PARP inhibitors are a type of targeted therapy. Ceralasertib may stop the growth of tumor cells and may kill them by blocking some of the enzymes needed for tumor cell growth. Giving biomarker selected personalized maintenance treatment with durvalumab, saruparib, ceralasertib or monalizumab may work better in treating patients with ES-SCLC.
STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have a prior or concurrent malignancy whose natural history or treatment (in the opinion of the treating physician) has the potential to interfere with the safety or efficacy assessment of the investigational regimen
STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have a history of limited stage small cell lung cancer
Treatment naïve and planning to receive frontline induction treatment with platinum plus etoposide in combination with durvalumab, OR,
Have initiated frontline induction therapy and completed at least 1 (≥ 1) cycle and at most 3 (≤ 3) cycles of platinum and etoposide. At most 2 (≤ 2) of these cycles could have been given without durvalumab
None
Parallel
Biospecimen Collection
Procedure/SurgeryUndergo tissue and blood sample collection
Ceralasertib
DrugGiven PO
Computed Tomography
Procedure/SurgeryUndergo CT scan
Durvalumab
Biological/VaccineGiven IV
Etoposide
DrugGiven etoposide
Magnetic Resonance Imaging
Procedure/SurgeryUndergo MRI
Monalizumab
Biological/VaccineGiven IV
Platinum Compound
DrugGiven platinum compound
Positron Emission Tomography
Procedure/SurgeryUndergo PET/CT scan
Saruparib
DrugGiven PO
Thoracic Radiation Therapy
RadiationUndergo thoracic radiation
6
Treatment groupsSee each treatment group below.
Screen success rate (Screening)
Will test participants' tissue specimens to determine their eligibility to 1 of the 3 treatment cohorts created based on their small cell lung cancer (SCLC) subtype and SLFN11 status. Will evaluate rate of participants who successfully get a cohort assignment based on SCLC subtype and SLNFN11 status, as appropriate.
Progression-free survival (PFS) (Cohort A)
Will compare PFS in participants with extensive stage SCLC (ES-SCLC) (subtypes A or N \& SLFN11 positive) or ES-SCLC (subtype P) randomized to durvalumab (MEDI4736) with or without saruparib (AZD5305) as maintenance therapy following induction chemoimmunotherapy with platinum, etoposide, and durvalumab (MEDI4736). Will be estimated using the Kaplan-Meier method. Associated confidence intervals about the median will be performed using the Brookmeyer-Crowley method. Binary proportions and associated confidence intervals will be calculated.
PFS (Cohort B)
Will compare PFS in participants with ES-SCLC subtypes A or N and SLFN11 negative randomized to durvalumab with or without ceralasertib (AZD6738) as maintenance therapy following induction chemoimmunotherapy with cisplatin or carboplatin, etoposide, and durvalumab (MEDI4736). Will be estimated using the Kaplan-Meier method. Associated confidence intervals about the median will be performed using the Brookmeyer-Crowley method.
PFS (Cohort C)
Will compare PFS participants with ES-SCLC subtype I randomized to durvalumab (MEDI4736) with or without monalizumab (IPH2201) as maintenance therapy following induction chemoimmunotherapy with cisplatin or carboplatin, etoposide, and durvalumab (MEDI4736). Will be estimated using the Kaplan-Meier method. Associated confidence intervals about the median will be performed using the Brookmeyer-Crowley method.
SCLC subtype status (Screening)
Will evaluate the percentage of participant tissue that are able to have SCLC subtype status determined.
SLFN11 status (Screening)
Will evaluate the percentage of participant tissue that are able to have SLFN11 status determined.
Assigned to a cohort and register to be randomized (Screening)
Will estimate the percentage of participants assigned to a cohort that register to be randomized.
Incidence of dose limiting toxicity (DLT) (Cohort A, safety run-in)
Will evaluate the safety of saruparib (AZD5305) in combination with durvalumab by estimating the rate of DLTs in the safety-run-in population. Will be assessed by treatment-related grade 3 or higher non hematologic toxicity, treatment-related grade 4 or higher hematologic toxicity, or any grade of treatment-related toxicity that in the opinion of the treating physician directly leads to that participant decision to drug discontinuation.
Bank specimens
Will bank specimens for future correlative studies.
Click on the lead sponsor to view all of their trials.
SWOG Cancer Research Network
Lead sponsor
National Cancer Institute (NCI)
Collaborator
