PRISM: PRecIsion in SCLC Via a Multicohort Study: Randomized Phase II Studies Evaluating Maintenance Durvalumab With or Without Biomarker-Directed Therapy for Extensive Stage Small Cell Lung Cancer (ES-SCLC)
概览
- 阶段
- 2 期
- 干预措施
- Biospecimen Collection
- 疾病 / 适应症
- Extensive Stage Lung Small Cell Carcinoma
- 发起方
- SWOG Cancer Research Network
- 入组人数
- 900
- 试验地点
- 49
- 主要终点
- Screen success rate (Screening)
- 状态
- 招募中
- 最后更新
- 3个月前
概览
简要总结
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.
详细描述
PRIMARY OBJECTIVES: I. To 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. (Screening) II. To compare progression-free survival (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). (Cohort A) III. To compare PFS in participants with ES-SCLC subtypes A or N \& SLFN11 negative randomized to durvalumab with or without ceralasertib (AZD6738) as maintenance therapy following induction chemoimmunotherapy with cisplatin or carboplatin, etoposide, and durvalumab (MEDI4736). (Cohort B) IV. To 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). (Cohort C) SECONDARY OBJECTIVES: I. To evaluate the percentage of participant tissue that are able to have SCLC subtype status determined. (Screening) II. To evaluate the percentage of participant tissue that are able to have SLFN11 status determined. (Screening) III. To estimate the percentage of participants assigned to a cohort that register to be randomized. (Screening) IV. To evaluate the safety of saruparib (AZD5305) in combination with durvalumab by estimating the rate of dose limiting toxicities reported during the first cycle of treatment in the safety-run-in population. (Cohort A) V. To compare PFS between the arms in the subset of participants with A or N subtype and SLFN11 positive. (Cohort A) VI. To compare overall survival (OS) between the arms. (Cohort A) VII. To evaluate the frequency and severity of toxicities by Common Terminology Criteria for Adverse Events (CTCAE) within each treatment arm. (Cohort A) VIII. To compare OS between the arms. (Cohort B) IX. To evaluate the frequency and severity of toxicities by CTCAE within each arm. (Cohort B) X. To compare OS between the arms. (Cohort C) XI. To evaluate the frequency and severity of toxicities by CTCAE within each arm. (Cohort C) TRANSLATIONAL MEDICINE OBJECTIVE: I. To bank specimens for future correlative studies. OUTLINE: INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab intravenously (IV) over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients are assigned to 1 of 3 cohorts and then randomized to 1 of 2 arms within each cohort to which they were assigned. COHORT A: Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. ARM 1: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib orally (PO) once daily (QD) on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. COHORT B: Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. ARM 1: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO twice daily (BID) on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. COHORT C: Patients with ES-SCLC determined to be subtype I. ARM 1: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. ARM 2: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo computed tomography (CT) scan or positron emission tomography (PET)/CT scan and CT scan or magnetic resonance imaging (MRI) throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study. After completion of study treatment, patients are followed up to 3 years.
研究者
入排标准
入选标准
- •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
- •STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must meet 1 of the following criteria prior to step 1:
- •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
- •NOTE: Participants must not have received immunotherapy other than durvalumab (e.g., atezolizumab) prior to enrollment
- •STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received any anti PD-1 or anti PD-L1 (including durvalumab \[MEDI4736\]) treatment for SCLC prior to starting frontline induction treatment for ES-SCLC
- •STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received anti PD-1 or anti PD-L1 other than durvalumab (MEDI4736) as part of frontline induction treatment for ES-SCLC. Participants must have not received atezolizumab, pembrolizumab, or nivolumab as part of frontline induction treatment
- •STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not have received any investigational agent for the treatment of ES-SCLC
- •STEP 1: SCREENING AND INDUCTION TREATMENT REGISTRATION: Participants must not be planning to receive any concurrent non-protocol directed chemotherapy, immunotherapy, biologic or hormonal therapy for SCLC treatment while receiving treatment on this study
排除标准
- 未提供
研究组 & 干预措施
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort A, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Saruparib
Cohort A, Arm 2 (durvalumab, saruparib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 positive or patients with subtype P ES-SCLC. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle and saruparib PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort B, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Ceralasertib
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort B, Arm 2 (durvalumab, ceralasertib)
Patients with ES-SCLC determined to be subtype A or N, and to be SLFN11 negative. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 8 and ceralasertib PO BID on days 1-7 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort C, Arm 1 (durvalumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Biospecimen Collection
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Computed Tomography
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Durvalumab
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Etoposide
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Magnetic Resonance Imaging
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Monalizumab
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Platinum Compound
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Positron Emission Tomography
Cohort C, Arm 2 (durvalumab, monalizumab)
Patients with ES-SCLC determined to be subtype I. INDUCTION: Patients may receive a platinum compound plus etoposide per standard care as well as durvalumab IV over 60 minutes on day 1 of each cycle. Cycles repeat every 28 days for 4-6 cycles in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients may undergo thoracic radiation as clinically indicated. MAINTENANCE: Patients receive durvalumab IV over 60 minutes on day 1 and monalizumab IV over 60 minutes on days 1 and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT scan or PET/CT scan and CT scan or MRI throughout the study. Patients also undergo tissue sample collection during screening and may undergo blood sample collection throughout the study.
干预措施: Thoracic Radiation Therapy
结局指标
主要结局
Screen success rate (Screening)
时间窗: Up to 3 years
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)
时间窗: From date of randomization to treatment within a cohort to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years
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)
时间窗: From date of randomization to treatment within a cohort to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years
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)
时间窗: From date of randomization to treatment within a cohort to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years
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.
次要结局
- SCLC subtype status (Screening)(Up to 3 years)
- SLFN11 status (Screening)(Up to 3 years)
- Assigned to a cohort and register to be randomized (Screening)(Up to 3 years)
- Incidence of dose limiting toxicity (DLT) (Cohort A, safety run-in)(During the first cycle of treatment (each cycle is 28 days))
- PFS (Cohort A)(From date of randomization to treatment within a cohort to date of first documentation of progression, symptomatic deterioration, or death due to any cause, assessed up to 3 years)
- Overall survival (OS) (Cohort A)(From date of randomization to treatment within a cohort to date of death due to any cause, assessed up to 3 years)
- Incidence of adverse events (Cohort A)(Up to 3 years)
- OS (Cohort B)(From date of randomization to treatment within a cohort to date of death due to any cause, assessed up to 3 years)
- Incidence of adverse events (Cohort B)(Up to 3 years)
- OS (Cohort C)(From date of randomization to treatment within a cohort to date of death due to any cause, assessed up to 3 years)
- Incidence of adverse events (Cohort C)(Up to 3 years)