Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study

Conditions

• Extensive Stage Lung Small Cell Carcinoma
• Lung Small Cell Carcinoma, A Subtype
• Lung Small Cell Carcinoma, I Subtype
• Lung Small Cell Carcinoma, N Subtype
• Lung Small Cell Carcinoma, P Subtype

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Biospecimen Collection — PROCEDURE
  Undergo tissue and blood sample collection
• Ceralasertib — DRUG
  Given PO
• Computed Tomography — PROCEDURE
  Undergo CT scan
• Durvalumab — BIOLOGICAL
  Given IV
• Etoposide — DRUG
  Given etoposide
• Magnetic Resonance Imaging — PROCEDURE
  Undergo MRI
• Monalizumab — BIOLOGICAL
  Given IV
• Platinum Compound — DRUG
  Given platinum compound
• Positron Emission Tomography — PROCEDURE
  Undergo PET/CT scan
• Saruparib — DRUG
  Given PO
• Thoracic Radiation Therapy — RADIATION
  Undergo thoracic radiation

Study Details

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.

Key Dates

Start date

Nov 6, 2025

Status verified

Jan 2026

Primary completion

Dec 31, 2028

Completion

Dec 31, 2029

Study Design

Enrollment

900 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: 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.
• Experimental: 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.
• Experimental: 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.
• Experimental: 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.
• Experimental: 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.
• Experimental: 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.

Primary Outcome Measure

Screen success rate (Screening) [ Time Frame: Up to 3 years ]

Locations (148)

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