Phase 3 Study of Sitravatinib Plus Nivolumab vs Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer (SAPPHIRE)

A Randomized Phase 3 Study of Sitravatinib in Combination With Nivolumab Versus Docetaxel in Patients With Advanced Non-Squamous Non-Small Cell Lung Cancer With Disease Progression On or After Platinum-Based Chemotherapy and Checkpoint Inhibitor Therapy SAPPHIRE

This study will compare the efficacy of the investigational agent sitravatinib in combination with nivolumab versus docetaxel in patients with advanced non-squamous NSCLC who have previously experienced disease progression on or after platinum-based chemotherapy and checkpoint inhibitor therapy.

Study Overview

• Status: Completed
• Conditions: Metastatic Non-Squamous Non-Small Cell Lung Cancer
• Intervention / Treatment: Biological: Nivolumab; Drug: Sitravatinib; Drug: Docetaxel

Detailed Description

Sitravatinib (MGCD516) is an orally-available, small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, TAM (Tyro3, AXL, MERTK) family, VEGFR family, PDGFR family, KIT, FLT3, TRK family, RET, DDR2, and selected EPH family members. Nivolumab is a human IgG monoclonal antibody that binds to the PD-1 receptor and selectively blocks the interaction with its ligands PD-L1 and PD-L2, thereby releasing PD-1 pathway mediated inhibition of the immune response, including anti-tumor immune response. RTKs have been implicated in mediating an immunosuppressive tumor microenvironment, which has emerged as a potential resistance mechanism to checkpoint inhibitor therapy. Inhibition of these RTKs by sitravatinib may augment anti-tumor immune response and improve outcomes by overcoming resistance to checkpoint inhibitor therapy.

• Study Type: Interventional
• Enrollment (Actual): 577
• Phase: Phase 3

Contacts and Locations

Study Locations

• Belgium
  • Brasschaat, Belgium, 2930
    • Local Institution - 005-201
  • Charleroi, Belgium, 6000
    • Local Institution - 005-200
  • Edegem, Belgium, 2650
    • Local Institution - 005-206
  • Ghent, Belgium, 9000
    • Local Institution - 005-202
  • Ghent, Belgium, 9000
    • Local Institution - 005-207
  • Roeselare, Belgium, 8800
    • Local Institution - 005-205
  • Ronse, Belgium, 9600
    • Local Institution - 005-204
  • Yvoir, Belgium, B-5530
    • Centre Hospitalier Universitaire Universite Catholique de Louvain - Site Godinne
• Canada
  • Québec, Canada, G1V 4G5
    • Local Institution - 005-258
  • Alberta
    • Calgary, Alberta, Canada, T2N 4N2
      • Local Institution - 005-259
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1C 6Z8
      • Local Institution - 005-250
    • Saint John, New Brunswick, Canada, E2L 4L2
      • Saint John Regional Hospital
  • Ontario
    • Hamilton, Ontario, Canada, L8V 5C2
      • Local Institution - 005-252
    • Toronto, Ontario, Canada, M5G 2M9
      • Local Institution - 005-251
    • Windsor, Ontario, Canada, N8W 2X3
      • Local Institution - 005-257
  • Quebec
    • Montreal, Quebec, Canada, H3A 0G4
      • Local Institution - 005-255
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 4H4
      • Saskatoon Cancer Centre
• France
  • Brest, France, 29200
    • Local Institution - 005-307
  • Bron, France, 69500
    • Local Institution - 005-310
  • Créteil, France, 94000
    • Local Institution - 005-311
  • Dijon, France, 21079
    • Local Institution - 005-303
  • Le Mans, France, 72037
    • Local Institution - 005-309
  • Limoges, France, 87042
    • Local Institution - 005-308
  • Lyon, France, 69008
    • Local Institution - 005-317
  • Marseille, France, 13009
    • Local Institution - 005-301
  • Marseille, France, 13015
    • Local Institution - 005-312
  • Montpellier, France, 34298
    • Local Institution - 005-313
  • Mulhouse, France, 68100
    • Local Institution - 005-306
  • Paris, France, 75018
    • Local Institution - 005-302
  • Rouen, France, 76031
    • Local Institution - 005-314
  • Saint-Herblain, France, 44805
    • Local Institution - 005-316
  • Strasbourg, France, 67200
    • Local Institution - 005-305
  • Villejuif, France, 94805
    • Local Institution - 005-304
• Germany
  • Bad Berka, Germany, 99437
    • Local Institution - 005-400
  • Berlin, Germany, 13125
    • Local Institution - 005-418
  • Bonn, Germany, 53127
    • Local Institution - 005-401
  • Cologne, Germany, 51109
    • Local Institution - 005-412
  • Essen, Germany, 45136
    • Local Institution - 005-419
  • Esslingen am Neckar, Germany, 73730
    • Local Institution - 005-406
  • Gauting, Germany, 82131
    • Local Institution - 005-403
  • Grohansdorf, Germany, 22927
    • Local Institution - 005-417
  • Halle, Germany, 06120
    • Local Institution - 005-408
  • Immenstadt im Allgäu, Germany, 87509
    • Local Institution - 005-411
  • Kassel, Germany, 34125
    • Local Institution - 005-416
  • Löwenstein, Germany, 74245
    • Local Institution - 005-410
  • Lübeck, Germany, 23538
    • Local Institution - 005-405
  • Mainz, Germany, 55131
    • Local Institution - 005-414
  • München, Germany, 81675
    • Local Institution - 005-413
  • München, Germany, 81925
    • Local Institution - 005-402
• Hungary
  • Budapest, Hungary, 1083
    • Local Institution - 005-454
  • Budapest, Hungary, 1121
    • Local Institution - 005-457
  • Budapest, Hungary, 1122
    • Local Institution - 005-455
  • Farkasgyepű, Hungary, 8582
    • Local Institution - 005-453
  • Győr, Hungary, 9023
    • Local Institution - 005-452
  • Szombathely, Hungary, 9700
    • Local Institution - 005-451
  • Tatabánya, Hungary, 2800
    • Local Institution - 005-450
  • Törökbálint, Hungary, 2045
    • Local Institution - 005-456
• Israel
  • Afula, Israel, 1834111
    • Local Institution - 005-500
  • Beer Yaakov, Israel, 7030000
    • Local Institution - 005-501
  • Beersheba, Israel, 84101
    • Local Institution - 005-504
  • Holon, Israel, 5822012
    • Local Institution - 005-502
  • Jerusalem, Israel, 9103102
    • Local Institution - 005-507
  • Ramat Gan, Israel, 5265601
    • Local Institution - 005-506
  • Zsfat, Israel, 1311001
    • Local Institution - 005-505
• Italy
  • Alessandria, Italy, 15121
    • Local Institution - 005-612
  • Bari, Italy, 70124
    • Local Institution - 005-602
  • Catania, Italy, 95123
    • Local Institution - 005-603
  • Cremona, Italy, 26100
    • Local Institution - 005-611
  • Lecce, Italy, 73100
    • Local Institution - 005-608
  • Meldola, Italy, 47014
    • Local Institution - 005-610
  • Milan, Italy, 20141
    • Local Institution - 005-606
  • Monza, Italy, 20900
    • Local Institution - 005-605
  • Napoli, Italy, 80131
    • Local Institution - 005-604
  • Parma, Italy, 43126
    • Local Institution - 005-600
  • Piacenza, Italy, 29100
    • Local Institution - 005-607
  • Pisa, Italy, 56126
    • Local Institution - 005-609
  • Roma, Italy, 00144
    • Local Institution - 005-614
  • Varese, Italy, 21100
    • Ospedale di Circolo e Fondazione Macchi
• Netherlands
  • 's-Hertogenbosch, Netherlands, 5223 GZ
    • Local Institution - 005-700
  • Amsterdam, Netherlands, 1066 CX
    • Local Institution - 005-703
  • Amsterdam, Netherlands, 1081 HV
    • Local Institution - 005-711
  • Breda, Netherlands, 4818 CK
    • Local Institution - 005-707
  • Dordrecht, Netherlands, 3318 AT
    • Local Institution - 005-713
  • Groningen, Netherlands, 9728 NT
    • Local Institution - 005-702
  • Maastricht, Netherlands, 6229 HX
    • Local Institution - 005-712
  • Nijmegen, Netherlands, 6525 GA
    • Local Institution - 005-714
  • Rotterdam, Netherlands, 3015 GD
    • Local Institution - 005-710
  • Rotterdam, Netherlands, 3045 PM
    • Local Institution - 005-705
  • The Hague, Netherlands, 2545 AA
    • Local Institution - 005-709
  • Utrecht, Netherlands, 3543 AZ
    • Local Institution - 005-701
  • Utrecht, Netherlands, 3584 CX
    • Local Institution - 005-708
  • Zwolle, Netherlands, 8025 AB
    • Local Institution - 005-706
• Spain
  • A Coruña, Spain, 15006
    • Local Institution - 005-807
  • Badalona, Spain, 08916
    • Local Institution - 005-800
  • Barcelona, Spain, 08003
    • Local Institution - 005-822
  • Barcelona, Spain, 08028
    • Local Institution - 005-811
  • Barcelona, Spain, 08035
    • Local Institution - 005-810
  • Jaén, Spain, 23007
    • Local Institution - 005-805
  • Las Palmas de Gran Canaria, Spain, 35016
    • Local Institution - 005-816
  • León, Spain, 24071
    • Local Institution - 005-817
  • Lugo, Spain, 27003
    • Local Institution - 005-812
  • Madrid, Spain, 28006
    • Hospital Universitario La Princesa
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid, Spain, 28006
    • Local Institution - 005-808
  • Madrid, Spain, 28027
    • Local Institution - 005-819
  • Madrid, Spain, 28034
    • Local Institution - 005-821
  • Madrid, Spain, 28040
    • Local Institution - 005-813
  • Madrid, Spain, 28040
    • Local Institution - 005-815
  • Madrid, Spain, 28041
    • Local Institution - 005-809
  • Majadahonda, Spain, 28222
    • Local Institution - 005-806
  • Málaga, Spain, 29009
    • Local Institution - 005-801
  • Oviedo, Spain, 33011
    • Local Institution - 005-803
  • Santiago de Compostela, Spain, 15706
    • Local Institution - 005-823
  • Valencia, Spain, 46009
    • IVO - Fundacion Instituto Valenciano de Oncologia
  • Valencia, Spain, 46026
    • Local Institution - 005-804
  • Vigo, Spain, 36312
    • Local Institution - 005-818
• Switzerland
  • Bern, Switzerland, 3010
    • Inselspital Universitatsspital Bern
  • Geneva, Switzerland, 1205
    • Hôpitaux universitaires de Genève
  • Lausanne, Switzerland, 1011
    • Centre Hospitalier Universitaire Vaudois Lausanne
  • Winterthur, Switzerland, 8401
    • Kantonsspital Winterthur
• United Kingdom
  • Cardiff, United Kingdom, CF14 2TL
    • Velindre University NHS Trust
  • Cornwall, United Kingdom, TR1 3LJ
    • Local Institution - 005-904
  • Leicester, United Kingdom, LE1 5WW
    • University Hospitals of Leicester NHS Trust
  • London, United Kingdom, SW3 6JJ
    • The Royal Marsden NHS Foundation Trust
  • London, United Kingdom, NW3 2QG
    • Local Institution - 005-908
  • London, United Kingdom, SW3 6JJ
    • Local Institution - 005-900
  • Manchester, United Kingdom, M20 4BX
    • The Christie NHS Foundation Trust
  • Middlesex, United Kingdom, HA6 2RN
    • Local Institution - 005-903
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35243
      • Local Institution - 005-164
    • Huntsville, Alabama, United States, 35805
      • Clearview Cancer Institute - Huntsville
  • Arizona
    • Glendale, Arizona, United States, 85304
      • Palo Verde Cancer Specialists - Glendale
    • Tucson, Arizona, United States, 85745
      • The Oncology Institute of Hope & Innovation - Tucson
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center
  • Arkansas
    • Jonesboro, Arkansas, United States, 72401
      • NEA Baptist Fowler Family Center for Cancer Care
    • Jonesboro, Arkansas, United States, 72401
      • Local Institution - 005-174
    • Springdale, Arkansas, United States, 72762
      • Highlands Oncology Group - Springdale
  • California
    • Bakersfield, California, United States, 93309
      • Comprehensive Blood and Cancer Center - Bakersfield
    • Beverly Hills, California, United States, 90211
      • Local Institution - 005-118
    • Fresno, California, United States, 93720
      • Local Institution - 005-171
    • Fullerton, California, United States, 92835
      • Providence Medical Foundation - Virginia K. Crosson Cancer Center - Fullerton
    • Long Beach, California, United States, 90813
      • Local Institution - 005-096
    • Los Alamitos, California, United States, 90720
      • Cancer and Blood Specialty Clinic
    • Los Angeles, California, United States, 90017
      • Los Angeles Hematology Oncology Medical Group
    • Los Angeles, California, United States, 90095
      • Local Institution - 005-185
    • Newport Beach, California, United States, 92663
      • Local Institution - 005-072
    • Northridge, California, United States, 91325
      • Local Institution - 005-109
    • Redlands, California, United States, 92373
      • Local Institution - 005-177
    • Riverside, California, United States, 92501
      • Local Institution - 005-112
    • San Francisco, California, United States, 94143
      • University of California San Francisco
    • San Marcos, California, United States, 92069
      • Local Institution - 005-176
    • Torrance, California, United States, 90505
      • Local Institution - 005-192
    • West Covina, California, United States, 91790
      • Local Institution - 005-090
    • Whittier, California, United States, 90602
      • Local Institution - 005-105
  • Colorado
    • Lafayette, Colorado, United States, 80026
      • Local Institution - 005-097
  • Connecticut
    • Norwich, Connecticut, United States, 06360
      • Eastern Connecticut Hematology and Oncology Associates
  • Florida
    • Fort Lauderdale, Florida, United States, 33308
      • Michael and Dianne Bienes Comprehensive Cancer Center
    • Fort Myers, Florida, United States, 33901
      • Local Institution - 005-120
    • Hollywood, Florida, United States, 33021
      • Memorial Regional Hospital
    • Lakeland, Florida, United States, 33805
      • Watson Clinic Cancer and Research Center
    • Miami Beach, Florida, United States, 33140
      • Mount Sinai Health System
    • Naples, Florida, United States, 34102
      • Local Institution - 005-120E
    • Ocala, Florida, United States, 34474
      • Local Institution - 005-079
    • Orlando, Florida, United States, 32804
      • Local Institution - 005-104
    • St. Petersburg, Florida, United States, 33705
      • SCRI - Florida Cancer Specialists - North Region Research Office
    • Tallahassee, Florida, United States, 32308
      • SCRI - Florida Cancer Specialists - Panhandle Research Office
    • West Palm Beach, Florida, United States, 33401
      • Local Institution - 005-154
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer & Blood Center (UCBC) - Athens
    • Atlanta, Georgia, United States, 30318
      • Local Institution - 005-146
    • Columbus, Georgia, United States, 31904
      • John B. Amos Cancer Center Research
    • Marietta, Georgia, United States, 30060
      • Local Institution - 005-119
  • Hawaii
    • Honolulu, Hawaii, United States, 96813
      • Straub Medical Center
  • Idaho
    • Coeur d'Alene, Idaho, United States, 83814
      • Local Institution - 005-191
  • Illinois
    • Chicago, Illinois, United States, 60625-3645
      • Local Institution - 005-151
    • Evanston, Illinois, United States, 60201
      • Local Institution - 005-110
    • Niles, Illinois, United States, 60714
      • Local Institution - 005-198
    • Skokie, Illinois, United States, 60077
      • Orchard Healthcare Research
    • Tinley Park, Illinois, United States, 60487
      • Healthcare Research Network - Tinley Park
  • Indiana
    • Fort Wayne, Indiana, United States, 46804
      • Fort Wayne Medical Oncology and Hematology - Fort Wayne South Office
    • Goshen, Indiana, United States, 46526
      • Local Institution - 005-122
    • Indianapolis, Indiana, United States, 46237
      • Franciscan Health Cancer Center Indianapolis
    • Lafayette, Indiana, United States, 47904
      • Local Institution - 005-150
  • Kansas
    • Westwood, Kansas, United States, 66205
      • Local Institution - 005-169
    • Wichita, Kansas, United States, 67214
      • Local Institution - 005-098
  • Kentucky
    • Danville, Kentucky, United States, 40422
      • Commonwealth Cancer Center - Frankfort
    • Louisville, Kentucky, United States, 40241
      • Local Institution - 005-153
  • Maine
    • Scarborough, Maine, United States, 04074
      • New England Cancer Specialists - Scarborough
  • Maryland
    • Rockville, Maryland, United States, 20850-6535
      • Local Institution - 005-178
  • Michigan
    • Detroit, Michigan, United States, 48201
      • Barbara Ann Karmanos Cancer Institute
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Minnesota
    • Minneapolis, Minnesota, United States, 55404
      • Local Institution - 005-127
    • Saint Louis Park, Minnesota, United States, 55426-5000
      • Local Institution - 005-159
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Jackson Oncology Associates - The Hederman Cancer Center
  • Missouri
    • Bolivar, Missouri, United States, 65613
      • Central Care Cancer Center - Bolivar
    • Kansas City, Missouri, United States, 64132
      • Kansas City Care Health Center - Research Medical Campus
  • Montana
    • Billings, Montana, United States, 59102
      • Sisters of Charity of Leavenworth Health St. Marys
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
      • Saint Francis Cancer Treatment Center
    • Omaha, Nebraska, United States, 68114
      • Methodist Hospital - Omaha
  • Nevada
    • Henderson, Nevada, United States, 89052
      • The Oncology Institute of Hope & Innovation - Henderson
    • Henderson, Nevada, United States, 89074
      • Local Institution - 005-152
  • New Jersey
    • Florham Park, New Jersey, United States, 07932
      • Local Institution - 005-142
    • Little Silver, New Jersey, United States, 07739
      • Local Institution - 005-163
    • Livingston, New Jersey, United States, 07039
      • Cooperman Barnabas Medical Center
    • Sparta, New Jersey, United States, 07871
      • Regional Cancer Care Associates - Sparta
  • New York
    • Johnson City, New York, United States, 13790
      • Local Institution - 005-123
    • Lake Success, New York, United States, 11042
      • Local Institution - 005-182
    • Port Jefferson Station, New York, United States, 11776
      • New York Cancer & Blood Specialists - Port Jefferson Medical Oncology
    • Stony Brook, New York, United States, 11794
      • Local Institution - 005-107
  • Ohio
    • Canton, Ohio, United States, 44708
      • Local Institution - 005-196
    • Cincinnati, Ohio, United States, 45242
      • USOR - Oncology Hematology Care - Blue Ash
    • Columbus, Ohio, United States, 43210
      • Local Institution - 005-181
    • Massillon, Ohio, United States, 44646
      • Tricounty Hematology and Oncology - Massillon
    • Toledo, Ohio, United States, 43623
      • Local Institution - 005-103
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Local Institution - 005-088
  • Oregon
    • Portland, Oregon, United States, 97213
      • Providence Portland Medical Center
    • Portland, Oregon, United States, 97239
      • Local Institution - 005-073
  • Pennsylvania
    • Horsham, Pennsylvania, United States, 19044
      • USOR - Alliance Cancer Specialists - Horsham (Abington Hematology Oncology Associates)
    • Philadelphia, Pennsylvania, United States, 19111
      • Local Institution - 005-186
  • Tennessee
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137A
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137B
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137C
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137D
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137E
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137F
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137G
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137H
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137I
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137J
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137K
    • Dickson, Tennessee, United States, 37055
      • Local Institution - 005-137L
    • Hendersonville, Tennessee, United States, 37075
      • Local Institution - 005-137M
    • Memphis, Tennessee, United States, 38120
      • Local Institution - 005-195
    • Nashville, Tennessee, United States, 37203
      • Local Institution - 005-137
  • Texas
    • Austin, Texas, United States, 78745
      • Local Institution - 005-134
    • Beaumont, Texas, United States, 77702
      • Local Institution - 005-075
    • Dallas, Texas, United States, 75203
      • Local Institution - 005-128
    • Dallas, Texas, United States, 75231
      • Local Institution - 005-129
    • Dallas, Texas, United States, 75246
      • Local Institution - 005-126
    • Denison, Texas, United States, 75020
      • USOR - Texas Oncology Northeast Texas - Denison
    • Denton, Texas, United States, 76201
      • Local Institution - 005-124
    • Fort Worth, Texas, United States, 76104
      • The Center for Cancer & Blood Disorders - Fort Worth
    • Houston, Texas, United States, 77030
      • Oncology Consultants - Texas Medical Center
    • Houston, Texas, United States, 77090
      • Millennium Research and Clinical Development
    • Houston, Texas, United States, 77070
      • Local Institution - 005-076
    • Irving, Texas, United States, 75063
      • USOR - US Oncology Investigational Products Center
    • McKinney, Texas, United States, 75071
      • Local Institution - 005-125
    • San Antonio, Texas, United States, 78240
      • Texas Oncology - San Antonio Medical Center
    • Sugar Land, Texas, United States, 77479
      • USOR - Texas Oncology - Sugar Land
    • Tyler, Texas, United States, 75702
      • USOR - Texas Oncology Northeast Texas - Cancer and Research Institute - Tyler
  • Virginia
    • Charlottesville, Virginia, United States, 22903
      • Local Institution - 005-144
    • Fredericksburg, Virginia, United States, 24408
      • Hematology Oncology Associates of Fredericksburg
    • Richmond, Virginia, United States, 23229
      • Virginia Cancer Institute - West End
  • Washington
    • Bellevue, Washington, United States, 98004
      • Overlake Medical Center and Clinics
    • Everett, Washington, United States, 98201
      • Local Institution - 005-082
    • Seattle, Washington, United States, 98109--1023
      • Local Institution - 005-111
    • Spokane, Washington, United States, 99218
      • Local Institution - 005-187
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties - Tacoma
    • Tacoma, Washington, United States, 98405
      • Local Institution - 005-081
    • Vancouver, Washington, United States, 98684
      • Local Institution - 005-136
  • Wisconsin
    • Appleton, Wisconsin, United States, 54911
      • ThedaCare Regional Cancer Center
    • Madison, Wisconsin, United States, 53792
      • Local Institution - 005-116
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of Non-Squamous Non-Small Cell Lung Cancer
• Receipt of at least one but not more than two prior treatment regimens in the advanced setting
• Prior treatment with PD-1/PD-L1 checkpoint inhibitor therapy and platinum-based chemotherapy in combination or in sequence (i.e., platinum-based chemotheraphy followed by checkpoint inhibitor therapy)
• Most recent treatment regimen must have included a checkpoint inhibitor therapy with radiographic disease progression on or after treatment
• Candidate to receive docetaxel as second or third line therapy

Exclusion Criteria:

• Uncontrolled brain metastases
• Tumors that have tested positive for EGFR, ROS1, ALK mutations, or ALK fusions
• Unacceptable toxicity with prior checkpoint inhibitor therapy
• Receipt of systemic anti-cancer therapy post checkpoint inhibitor therapy, other than maintenance chemotherapy
• Impaired heart function

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nivolumab and Sitravatinib; Nivolumab will be administered by intravenous infusion over 30 minutes at 240 mg every 2 weeks or at 480 mg every 4 weeks. Sitravatinib capsules will be administered orally, once daily.	Biological: Nivolumab; Nivolumab is an antibody directed at the programmed death receptor-1 (PD-1), blocking its interaction with PD-L1 and PD-L2.; Other Names: Opdivo; Drug: Sitravatinib; Sitravatinib is a small molecule inhibitor of receptor tyrosine kinases.; Other Names: MGCD516
Active Comparator: Docetaxel; Docetaxel will be administered by intravenous infusion at 75 mg/m2 over 1 hour every 3 weeks.	Drug: Docetaxel; Docetaxel is an anti-neoplastic agent that acts by disrupting the microtubular network in cells.; Other Names: Taxotere

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as time from date of randomization to date of death due to any cause. Patients who did not die on study are censored at the date of the last on-study follow-up that the patient was known to be alive (including follow-up data). Results obtained via Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.	From randomization date to date of death due to any cause (Up to approximately 44 months)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Treatment-Emergent Adverse Event (TEAEs)	An adverse event (AE) is any reaction, side effect or other undesirable medical event that occurs during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. Serious adverse events (SAE) are defined as any AE which results in death; is life-threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability/incapacity; is a congenital anomaly/birth defect; constitutes an important medical event. A treatment emergent AE (TEAE) is an AE that occurs after the first dose of any study treatment or any preexisting condition that increases in severity after the first dose of study treatment. Adverse events were graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 (Grade 3 = Severe, Grade 4 = Life-threatening, Grade 5 = Death).	From first dose up to 28 days post last dose, and up to 100 days post last dose of nivolumab for immune-related AEs (Up to maximum of 38 months)
Number of Participants With Treatment-Emergent Adverse Events (TEAE) Leading to Study Drug Discontinuation	An adverse event (AE) is any reaction, side effect or other undesirable medical event that occurs during participation in a clinical trial, regardless of treatment group or suspected causal relationship to study treatment. A treatment emergent AE (TEAE) is an AE that occurs after the first dose of any study treatment or any preexisting condition that increases in severity after the first dose of study treatment.	From first dose up to 28 days post last dose, and up to 100 days post last dose of nivolumab for immune-related AEs (Up to maximum of 38 months)
Number of Participants With Maximum Post Baseline Hematology Grade Results	The severity of hematology results were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0); Hematology parameters were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. Number of participants with maximum post baseline grades is presented. Grade 0 is defined as absence of an AE or within normal limits. Baseline is defined as the last pre-dose assessment.	From first dose up to 28 days post last dose (Up to an average of 7.5 months and maximum of 36 months)
Number of Participants With Maximum Post Baseline Chemistry Grade Results	The severity of chemistry results were graded based upon the participants symptoms according to the Common Terminology Criteria for Adverse Events (CTCAE, Version 5.0); Chemistry parameters were evaluated for severity according to the following scale: Grade 1 = Mild - transient or mild discomfort; no medical intervention required; Grade 2 = Moderate - mild to moderate limitation in activity; Grade 3 = Severe; Grade 4 = Life threatening; Grade 5 = Death. Number of participants with maximum post baseline grades is presented. Grade 0 is defined as absence of an AE or within normal limits. Baseline is defined as the last pre-dose assessment.	From first dose up to 28 days post last dose (Up to an average of 7.5 months and maximum of 36 months)
Objective Response Rate (ORR) Per Central Radiographic Assessment	ORR is defined as percentage of participants with confirmed complete response (CR) or partial response (PR) per RECIST version 1.1 recorded from randomization until disease progression or start of new anti-cancer therapy. Patients who cannot be assessed for response are counted as non-responders. CR is defined as complete disappearance of all target lesions with the exception of nodal disease; PR is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions.	From randomization until disease progression or start of new anti-cancer therapy (Up to approximately 44 months)
Duration of Response (DOR) Per Central Radiographic Assessment	DOR is defined as the time from date of the first documentation of confirmed objective response (CR or PR) to the first documentation of disease progression (PD) or to death due to any cause in the absence of documented PD. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions. Results obtained via Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.	From randomization to the first documentation of disease progression (PD) or to death due to any cause in the absence of documented PD (Up to approximately 44 months)
Clinical Benefit Rate Per Central Radiographic Assessment	CBR is defined as the percentage of patients documented to have a confirmed CR, confirmed PR, or SD, according to RECIST 1.1 as the best response. Complete response (CR) is defined as complete disappearance of all target lesions with the exception of nodal disease. Partial response (PR) is defined as >=30% decrease under baseline of the sum of diameters of all target measurable lesions. Stable Disease (SD) is concluded when the response does not qualify for CR, PR or Progression. Progression is defined as 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm.	From randomization until disease progression or start of new anti-cancer therapy (Up to approximately 44 months)
Progression-Free Survival (PFS) Per Central Radiographic Assessment	PFS is defined as the time from randomization to the date of the first documentation of objective disease progression or death due to any cause. Progressive Disease (PD) is defined as a 20% increase in the sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum is observed during therapy) with a minimum absolute increase of 5 mm, or unequivocal progression of pre-existing non-target lesions. Censoring was assigned on the date of the last tumor assessment if no assessment of tumor progression is identified and the patient does not die while on study. Patients with no evaluation of disease after first study treatment will have PFS censored on the date of randomization. Patients who start new anti-cancer therapy prior to documented PD will be censored at the date of the last tumor assessment prior to the start of the new therapy. Results obtained using Kaplan-Meier estimation, Brookmeyer and Crowley (1982) method.	From randomization to the date of the first documentation of objective disease progression or death due to any cause (Up to approximately 44 months)
1-Year Survival Rate	1-Year Survival will be defined as the percentage of participants surviving at 1 year after the first dose. Results obtained via Kaplan-Meier estimation, Greenwood's formula (1980).	At 12 months from first dose
Change From Baseline in the Lung Cancer Symptom Scale (LCSS) Average Total Score	The LCSS is a lung cancer specific measure of quality of life and includes 9 questions, including patient-reported ratings of six symptoms (appetite loss, fatigue, cough, dyspnea, hemoptysis, pain) and three summary items (symptom distress, activity level, overall quality of life) using 100-mm visual analogue scales ranging from 0 (lowest rating) to 100 (highest rating). The average total score = is a sum of items 1 to 9 divided by the total number of items (sum of items 1 to 9) / 9).	Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.
Change From Baseline in the European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) - Health Utility Index (HUI)	The European Quality of Life 5D-5L Scale (EQ-5D-5L) assesses general health-related quality of life. Health is defined in 5 dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems, and extreme problems. Responses are coded so that a '1' indicates no problem, and '5' indicates the most serious problem. The responses for the 5 dimensions are combined in a 5-digit number. The EQ-5D-5L health utility index (HUI) is assessed using the Crosswalk algorithm for France based on the individual responses to the 5 EQ-5D-5L domains ranging from -0.530 to 1.000. The smallest change considered clinically meaningful, is defined as a score difference of 0.08 points.	Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.
Change From Baseline in the European Quality of Life Five Dimensions Questionnaire (EQ-5D-5L) - Visual Analogue Score (VAS)	The Visual Analogue Score (VAS) is a component of the EQ-5D-5L and assesses the patient's self-rated health using a vertical visual analogue scale where numbered 0 (the worst health you can image) to 100 (the best health you can imageine). The smallest change considered clinically meaningful, is defined as a score difference of 7 points.	Clinic visit closest to the disease evaluation on weeks 9, 17, 25, 33, 41, 49.
Sitravatinib Plasma Concentration by Time Point		0.5 hours post dose on cycle 1 (day 1) and 5 hours post dose on cycle 1 (day 1 and 15), and pre-dose on cycle 1 (day 15), and cycle 2, 3, and 5 (day 1)

Collaborators and Investigators

• Sponsor: Mirati Therapeutics Inc.
• Collaborators: Bristol-Myers Squibb
• Investigators: Study Director: Bristol-Myers Squibb, Bristol-Myers Squibb

Publications and helpful links

Helpful Links

• BMS Clinical Trial Information
• BMS Clinical Trial Patient Recruiting

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2019
• Primary Completion (Actual): March 20, 2023
• Study Completion (Actual): September 30, 2025

Study Registration Dates

• First Submitted: April 4, 2019
• First Submitted That Met QC Criteria: April 4, 2019
• First Posted (Actual): April 8, 2019

Study Record Updates

• Last Update Posted (Estimated): October 21, 2025
• Last Update Submitted That Met QC Criteria: October 16, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Docetaxel; NSCLC; Sitravatinib; Nivolumab; Checkpoint inhibitor; MGCD516; SAPPHIRE
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Organic Chemicals; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Taxoids; Cyclodecanes; Diterpenes; Docetaxel; Nivolumab; sitravatinib
• Other Study ID Numbers: CA248-0001 (Other Identifier: Bristol-Myers Squibb Protocol ID); 516-005 (Other Identifier: Mirati Therapeutics Protocol ID)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No