Using Biomarker Tests to Select and Test New, Personalized Treatments for Extensive Stage Small Cell Lung Cancer, PRISM Study
Start Date
11/6/2025
Completion Date
12/31/2029
Summary
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.
Detailed Description
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.
Eligibility Criteria
Age Range: 18 years to No maximum
Interventions
Biospecimen Collection
Ceralasertib
Computed Tomography
Durvalumab
Etoposide
Magnetic Resonance Imaging
Monalizumab
Platinum Compound
Positron Emission Tomography
Saruparib
Thoracic Radiation Therapy
Conditions
Locations
Loma Linda University Medical Center
Loma Linda, California 92354
United States
Eisenhower Medical Center
Rancho Mirage, California 92270
United States
University of California Davis Comprehensive Cancer Center
Sacramento, California 95817
United States
UCHealth University of Colorado Hospital
Aurora, Colorado 80045
United States
UCHealth Memorial Hospital Central
Colorado Springs, Colorado 80909
United States
Memorial Hospital North
Colorado Springs, Colorado 80920
United States
Poudre Valley Hospital
Fort Collins, Colorado 80524
United States
Cancer Care and Hematology-Fort Collins
Fort Collins, Colorado 80528
United States
Lutheran Hospital - Cancer Centers of Colorado
Golden, Colorado 80401
United States
UCHealth Greeley Hospital
Greeley, Colorado 80631
United States
Medical Center of the Rockies
Loveland, Colorado 80538
United States
Smilow Cancer Hospital-Derby Care Center
Derby, Connecticut 06418
United States
Smilow Cancer Hospital Care Center-Fairfield
Fairfield, Connecticut 06824
United States
Smilow Cancer Hospital Care Center - Guilford
Guilford, Connecticut 06437
United States
Yale University
New Haven, Connecticut 06520
United States
Yale-New Haven Hospital North Haven Medical Center
North Haven, Connecticut 06473
United States
Smilow Cancer Hospital-Torrington Care Center
Torrington, Connecticut 06790
United States
Smilow Cancer Hospital Care Center-Trumbull
Trumbull, Connecticut 06611
United States
Smilow Cancer Hospital-Waterbury Care Center
Waterbury, Connecticut 06708
United States
Smilow Cancer Hospital Care Center - Waterford
Waterford, Connecticut 06385
United States
Helen F Graham Cancer Center
Newark, Delaware 19713
United States
Medical Oncology Hematology Consultants PA
Newark, Delaware 19713
United States
Lewis Cancer and Research Pavilion at Saint Joseph's/Candler
Savannah, Georgia 31405
United States
Kootenai Health - Coeur d'Alene
Coeur d'Alene, Idaho 83814
United States
Saint Alphonsus Cancer Care Center-Nampa
Nampa, Idaho 83687
United States
Kootenai Clinic Cancer Services - Post Falls
Post Falls, Idaho 83854
United States
Kootenai Clinic Cancer Services - Sandpoint
Sandpoint, Idaho 83864
United States
Northwestern University
Chicago, Illinois 60611
United States
Northwestern Medicine Cancer Center Kishwaukee
DeKalb, Illinois 60115
United States
Northwestern Medicine Cancer Center Delnor
Geneva, Illinois 60134
United States
Northwestern Medicine Glenview Outpatient Center
Glenview, Illinois 60026
United States
Northwestern Medicine Grayslake Outpatient Center
Grayslake, Illinois 60030
United States
Northwestern Medicine Lake Forest Hospital
Lake Forest, Illinois 60045
United States
Loyola University Medical Center
Maywood, Illinois 60153
United States
Northwestern Medicine Oak Brook
Oak Brook, Illinois 60523
United States
Northwestern Medicine Orland Park
Orland Park, Illinois 60462
United States
Northwestern Medicine Cancer Center Warrenville
Warrenville, Illinois 60555
United States
Mary Greeley Medical Center
Ames, Iowa 50010
United States
McFarland Clinic - Ames
Ames, Iowa 50010
United States
UI Health Care Mission Cancer and Blood - Ankeny Clinic
Ankeny, Iowa 50023
United States
McFarland Clinic - Boone
Boone, Iowa 50036
United States
Mercy Hospital
Cedar Rapids, Iowa 52403
United States
Oncology Associates at Mercy Medical Center
Cedar Rapids, Iowa 52403
United States
UI Health Care Mission Cancer and Blood - West Des Moines Clinic
Clive, Iowa 50325
United States
Iowa Methodist Medical Center
Des Moines, Iowa 50309
United States
UI Health Care Mission Cancer and Blood - Des Moines Clinic
Des Moines, Iowa 50309
United States
Mercy Medical Center - Des Moines
Des Moines, Iowa 50314
United States
UI Health Care Mission Cancer and Blood - Laurel Clinic
Des Moines, Iowa 50314
United States
McFarland Clinic - Trinity Cancer Center
Fort Dodge, Iowa 50501
United States
McFarland Clinic - Jefferson
Jefferson, Iowa 50129
United States
McFarland Clinic - Marshalltown
Marshalltown, Iowa 50158
United States
UI Health Care Mission Cancer and Blood - Waukee Clinic
Waukee, Iowa 50263
United States
The Iowa Clinic PC
West Des Moines, Iowa 50266
United States
University of Kansas Clinical Research Center
Fairway, Kansas 66205
United States
University of Kansas Cancer Center
Kansas City, Kansas 66160
United States
The University of Kansas Cancer Center - Olathe
Olathe, Kansas 66061
United States
University of Kansas Cancer Center-Overland Park
Overland Park, Kansas 66210
United States
Salina Regional Health Center
Salina, Kansas 67401
United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas 66205
United States
Baptist Health Corbin
Corbin, Kentucky 40701
United States
Baptist Health Lexington
Lexington, Kentucky 40503
United States
Baptist Health Hamburg
Lexington, Kentucky 40509
United States
University of Maryland/Greenebaum Cancer Center
Baltimore, Maryland 21201
United States
Tufts Medical Center
Boston, Massachusetts 02111
United States
Lahey Hospital and Medical Center
Burlington, Massachusetts 01805
United States
Lahey Medical Center-Peabody
Peabody, Massachusetts 01960
United States
Trinity Health IHA Medical Group Hematology Oncology - Brighton
Brighton, Michigan 48114
United States
Trinity Health IHA Medical Group Hematology Oncology - Canton
Canton, Michigan 48188
United States
Trinity Health IHA Medical Group Hematology Oncology - Chelsea Hospital
Chelsea, Michigan 48118
United States
Henry Ford Health Saint John Hospital
Detroit, Michigan 48236
United States
Henry Ford River District Hospital
East China Township, Michigan 48054
United States
Henry Ford Saint John Hospital - Academic
Grosse Pointe Woods, Michigan 48236
United States
Henry Ford Saint John Hospital - Breast
Grosse Pointe Woods, Michigan 48236
United States
Henry Ford Saint John Hospital - Van Elslander
Grosse Pointe Woods, Michigan 48236
United States
University of Michigan Health - Sparrow Lansing
Lansing, Michigan 48912
United States
Trinity Health Saint Mary Mercy Livonia Hospital
Livonia, Michigan 48154
United States
Henry Ford Saint John Hospital - Macomb Medical
Macomb, Michigan 48044
United States
Henry Ford Warren Hospital - Breast Macomb
Macomb, Michigan 48044
United States
Trinity Health Saint Joseph Mercy Oakland Hospital
Pontiac, Michigan 48341
United States
Henry Ford Health Warren Hospital
Warren, Michigan 48093
United States
Henry Ford Madison Heights Hospital - Breast
Warren, Michigan 48093
United States
Henry Ford Warren Hospital - GLCMS
Warren, Michigan 48093
United States
Trinity Health IHA Medical Group Hematology Oncology Ann Arbor Campus
Ypsilanti, Michigan 48197
United States
Sanford Joe Lueken Cancer Center
Bemidji, Minnesota 56601
United States
Essentia Health Saint Joseph's Medical Center
Brainerd, Minnesota 56401
United States
Mercy Hospital
Coon Rapids, Minnesota 55433
United States
Essentia Health - Deer River Clinic
Deer River, Minnesota 56636
United States
Essentia Health Cancer Center
Duluth, Minnesota 55805
United States
Fairview Southdale Hospital
Edina, Minnesota 55435
United States
Essentia Health Hibbing Clinic
Hibbing, Minnesota 55746
United States
Saint John's Hospital - Healtheast
Maplewood, Minnesota 55109
United States
Abbott-Northwestern Hospital
Minneapolis, Minnesota 55407
United States
Hennepin County Medical Center
Minneapolis, Minnesota 55415
United States
New Ulm Medical Center
New Ulm, Minnesota 56073
United States
Park Nicollet Clinic - Saint Louis Park
Saint Louis Park, Minnesota 55416
United States
Regions Hospital
Saint Paul, Minnesota 55101
United States
United Hospital
Saint Paul, Minnesota 55102
United States
Essentia Health Sandstone
Sandstone, Minnesota 55072
United States
Essentia Health Virginia Clinic
Virginia, Minnesota 55792
United States
University of Kansas Cancer Center - Briarcliff
Kansas City, Missouri 64116
United States
University of Kansas Cancer Center - North
Kansas City, Missouri 64154
United States
University of Kansas Cancer Center - Lee's Summit
Lee's Summit, Missouri 64064
United States
Mercy Hospital South
St Louis, Missouri 63128
United States
Mercy Hospital Saint Louis
St Louis, Missouri 63141
United States
Community Hospital of Anaconda
Anaconda, Montana 59711
United States
Billings Clinic Cancer Center
Billings, Montana 59101
United States
Bozeman Health Deaconess Hospital
Bozeman, Montana 59715
United States
Benefis Sletten Cancer Institute
Great Falls, Montana 59405
United States
Community Medical Center
Missoula, Montana 59804
United States
Roswell Park Cancer Institute
Buffalo, New York 14263
United States
University of Rochester
Rochester, New York 14642
United States
Wilmot Cancer Institute at Webster
Webster, New York 14580
United States
FirstHealth of the Carolinas-Moore Regional Hospital
Pinehurst, North Carolina 28374
United States
Sanford Bismarck Medical Center
Bismarck, North Dakota 58501
United States
Essentia Health Cancer Center-South University Clinic
Fargo, North Dakota 58103
United States
Sanford Broadway Medical Center
Fargo, North Dakota 58122
United States
Sanford Roger Maris Cancer Center
Fargo, North Dakota 58122
United States
Aultman Health Foundation
Canton, Ohio 44710
United States
Miami Valley Hospital South
Centerville, Ohio 45459
United States
Miami Valley Hospital
Dayton, Ohio 45409
United States
Premier Blood and Cancer Center
Dayton, Ohio 45409
United States
Miami Valley Hospital North
Dayton, Ohio 45415
United States
Atrium Medical Center-Middletown Regional Hospital
Franklin, Ohio 45005-1066
United States
Miami Valley Cancer Care and Infusion
Greenville, Ohio 45331
United States
Upper Valley Medical Center
Troy, Ohio 45373
United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma 73104
United States
Providence Newberg Medical Center
Newberg, Oregon 97132
United States
Providence Willamette Falls Medical Center
Oregon City, Oregon 97045
United States
Providence Portland Medical Center
Portland, Oregon 97213
United States
Providence Saint Vincent Medical Center
Portland, Oregon 97225
United States
Saint Joseph's/Candler - Bluffton Campus
Bluffton, South Carolina 29910
United States
Prisma Health Cancer Institute - Spartanburg
Boiling Springs, South Carolina 29316
United States
Prisma Health Cancer Institute - Easley
Easley, South Carolina 29640
United States
Tidelands Georgetown Memorial Hospital
Georgetown, South Carolina 29440
United States
Prisma Health Cancer Institute - Butternut
Greenville, South Carolina 29605
United States
Prisma Health Cancer Institute - Faris
Greenville, South Carolina 29605
United States
Prisma Health Cancer Institute - Eastside
Greenville, South Carolina 29615
United States
Prisma Health Cancer Institute - Greer
Greer, South Carolina 29650
United States
Prisma Health Cancer Institute - Seneca
Seneca, South Carolina 29672
United States
Sanford Cancer Center Oncology Clinic
Sioux Falls, South Dakota 57104
United States
Sanford USD Medical Center - Sioux Falls
Sioux Falls, South Dakota 57117-5134
United States
M D Anderson Cancer Center
Houston, Texas 77030
United States
VCU Massey Cancer Center at Stony Point
Richmond, Virginia 23235
United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia 23298
United States
VCU Community Memorial Health Center
South Hill, Virginia 23970
United States
VCU Health Tappahannock Hospital
Tappahannock, Virginia 22560
United States
Duluth Clinic Ashland
Ashland, Wisconsin 54806
United States
Gundersen Lutheran Medical Center
La Crosse, Wisconsin 54601
United States