First-line Treatment of Participants With Stage IV Squamous Non-Small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin
SQUIRE
A Randomized, Multicenter, Open-Label Phase 3 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) Versus Gemcitabine-Cisplatin Chemotherapy Alone in the First-Line Treatment of Patients With Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)
4 other identifiers
interventional
1,093
25 countries
179
Brief Summary
The research study is testing the investigational drug necitumumab (IMC-11F8) in the treatment of advanced non-small cell lung cancer. The aim of this study is to determine if necitumumab, given together with a standard chemotherapy combination consisting of cisplatin and gemcitabine will be more effective in improving participant disease than the standard chemotherapy combination alone.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_3
Started Jan 2010
Longer than P75 for phase_3
179 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
September 18, 2009
CompletedFirst Posted
Study publicly available on registry
September 22, 2009
CompletedStudy Start
First participant enrolled
January 7, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 17, 2013
CompletedResults Posted
Study results publicly available
June 27, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
May 30, 2024
CompletedJune 18, 2025
May 1, 2025
3.4 years
September 18, 2009
December 21, 2015
May 30, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Overall Survival Time (OS)
Overall survival is defined as the time from randomization to death from any cause. Participants who do not die at the end of the extended follow-up period, or were lost to follow-up during the study, were censored at the last date they were known to be alive. OS was estimated by the Kaplan-Meier method.
Randomization to Death from Any Cause (Up to 31 Months)
Secondary Outcomes (8)
Progression-Free Survival (PFS)
Randomization to Measured Progressive Disease or Death from Any Cause (Up to 31 Months)
Percentage of Participants Achieving Complete Response (CR) and Partial Response (PR) (Objective Response Rate [ORR])
Baseline to Measured Progressive Disease (Up to 31 Months)
Time to Treatment Failure (TTF)
Randomization to Measured Progressive Disease, Death From Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up to 31 Months)
Mean Change From Baseline in Patient Reported Outcomes (PRO) Using the European Quality of Life-5 Dimension (EQ-5D)
Baseline, Cycle 6 (Cycle = 3 Weeks)
Mean Change From Baseline in PRO Using the Outcomes Lung Cancer Symptom Scale (LCSS)
Baseline, Cycle 6 (Cycle = 3 Weeks)
- +3 more secondary outcomes
Study Arms (2)
Necitumumab + Gemcitabine + Cisplatin
EXPERIMENTALNecitumumab: 800 milligrams (mg) I.V. infusion on Days 1 and 8 of every 3 week cycle. Continues until progressive disease, toxicity, noncompliance, or withdrawal. Gemcitabine: 1250 milligrams/square meter (mg/m2) on Days 1 and 8 of every 3 week cycle. Continues for a maximum of six cycles. Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
Gemcitabine + Cisplatin
ACTIVE COMPARATORGemcitabine: 1250 mg/m2 on Days 1 and 8 of every 3 week cycle. Continues for a maximum of six cycles. Cisplatin: 75 mg/m2 IV on Day 1 of every 3 week cycle. Continues for a maximum of six cycles.
Interventions
Administered intravenously. Continues until progressive disease, toxicity, noncompliance, or withdrawal.
Administered intravenously. Continues for a maximum of six cycles.
Administered intravenously. Continues for a maximum of six cycles.
Eligibility Criteria
You may qualify if:
- Has histologically or cytologically confirmed squamous NSCLC
- Has Stage IV disease at the time of study entry
- Measurable or nonmeasurable disease at the time of study entry as defined by the Response Evaluation Criteria in Solid Tumors (RECIST 1.0) (participants with only truly nonmeasurable disease are not eligible)
- Has resolution to Grade ≤ 1 of all clinically significant toxic effects of prior chemotherapy, surgery, radiotherapy, or hormonal therapy (with the exception of alopecia)
- Has adequate hepatic function
- Has adequate renal function
- Has adequate hematologic function
- If female, is surgically sterile, postmenopausal, or compliant with a highly effective contraceptive method (failure rate \< 1%) during and for 6 months after the treatment period (oral hormonal contraception alone is not considered highly effective and must be used in combination with a barrier method)
- If male, the participant is surgically sterile or compliant with a highly effective contraceptive regimen during and for 6 months after the treatment period
- Female participants of childbearing potential must have a negative serum pregnancy test within 7 days prior to randomization
- Has archived tumor tissue available for analysis of EGFR and KRAS mutation status (by PCR) and EGFR gene copy number (by FISH); minimum of four slides, paraffin-embedded tissue, required
You may not qualify if:
- Has nonsquamous NSCLC (adenocarcinoma/large cell or other)
- Has received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
- Has received previous chemotherapy for advanced NSCLC (participants who have received adjuvant chemotherapy are eligible if the last administration of the prior adjuvant regimen occurred at least 1 year prior to randomization)
- Has undergone major surgery or received any investigational therapy in the 4 weeks prior to randomization
- Has undergone chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
- Has brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants. Participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible
- Has superior vena cava syndrome contraindicating hydration
- Has current clinically-relevant coronary artery disease or uncontrolled congestive heart failure
- Has experienced myocardial infarction within 6 months prior to randomization
- Has an ongoing or active infection (requiring antibiotics), including active tuberculosis or known infection with the human immunodeficiency virus
- Has a history of significant neurological or psychiatric disorders, including dementia, seizures, or bipolar disorder
- Has any National Cancer Institute - Common Terminology Criteria for Adverse Events (NCI-CTCAE) Version 3.0 Grade ≥ 2 peripheral neuropathy
- Has significant third space fluid retention, requiring repeated drainage
- Has any other serious uncontrolled medical disorders or psychological conditions that would, in the opinion of the investigator, limit the participant's ability to complete the study or sign an informed consent document
- Has a known allergy / history of hypersensitivity reaction to any of the treatment components, including any ingredient used in the formulation of necitumumab (IMC-11F8), or any other contraindication to one of the administered treatments
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Eli Lilly and Companylead
- Parexelcollaborator
- PPD Development, LPcollaborator
- Medidata Solutionscollaborator
- Laboratory Corporation of Americacollaborator
- University of Colorado, Denvercollaborator
- Thermo Fisher Scientific FScollaborator
- ICON Clinical Researchcollaborator
- Pacific Biomarkerscollaborator
- Sysmex Inostics GmbHcollaborator
- Intertekcollaborator
Study Sites (182)
ImClone Investigational Site
Chandler, Arizona, 85224, United States
ImClone Investigational Site
Fayetteville, Arkansas, 72703, United States
ImClone Investigational Site
Sacramento, California, 95816, United States
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Galesburg, Illinois, 61401, United States
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Goshen, Indiana, 46526, United States
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Wichita, Kansas, 67214, United States
ImClone Investigational Site
Hazard, Kentucky, 41701, United States
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Baltimore, Maryland, 21204, United States
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Jefferson City, Missouri, 65109, United States
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Lincoln, Nebraska, 68510, United States
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New York, New York, 10065, United States
ImClone Investigational Site
Akron, Ohio, 44304, United States
ImClone Investigational Site
Camp Hill, Pennsylvania, 17011, United States
ImClone Investigational Site
Memphis, Tennessee, 38104, United States
ImClone Investigational Site
Fairfax, Virginia, 22031, United States
ImClone Investigational Site
Garran, New South Wales, 2605, Australia
ImClone Investigational Site
Westmead, New South Wales, 2145, Australia
ImClone Investigational Site
Wollongong, New South Wales, 2500, Australia
ImClone Investigational Site
East Bentleigh, Victoria, 3165, Australia
ImClone Investigational Site
Geelong, Victoria, 3220, Australia
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Linz, 4020, Austria
ImClone Investigational Site
Vienna, 1090, Austria
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Vienna, 1130, Austria
ImClone Investigational Site
Duffel, 2570, Belgium
ImClone Investigational Site
Liège, 4000, Belgium
ImClone Investigational Site
Namur, 5000, Belgium
ImClone Investigational Site
Barretos, 14784-400, Brazil
ImClone Investigational Site
Brasilia, Distrito Federal, 70710-904, Brazil
ImClone Investigational Site
Goiânia, 74884-606, Brazil
ImClone Investigational Site
Ijuí, 98700-000, Brazil
ImClone Investigational Site
Itajaí, 88301-220, Brazil
ImClone Investigational Site
Lajeado, 95900-000, Brazil
ImClone Investigational Site
Porto Alegre/RS, 90610-000, Brazil
ImClone Investigational Site
Salvador, 40050-410, Brazil
ImClone Investigational Site
Santo André, 09090-780, Brazil
ImClone Investigational Site
São Paulo, 01224-010, Brazil
ImClone Investigational Site
São Paulo - SP, 01246-000, Brazil
ImClone Investigational Site
Saint John, New Brunswick, E2L 4L2, Canada
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Brampton, Ontario, L6R 3J7, Canada
ImClone Investigational Site
Saskatoon, Saskatchewan, S7N 4H4, Canada
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Dubrovnik, 20000, Croatia
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Pula, 52100, Croatia
ImClone Investigational site
Zagreb, 10000, Croatia
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Brest, 29609, France
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Caen, 14076, France
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Draguignan, 83300, France
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Grenoble, 38043, France
ImClone Investigational Site
Le Mans, 72000, France
ImClone Investigational Site
Le Mans, 72037, France
ImClone Investigational Site
Lille, 59020, France
ImClone Investigational Site
Lyon, 69373, France
ImClone Investigational Site
Marseille, 13009, France
ImClone Investigational Site
Paris, 75005, France
ImClone Investigational Site
Paris, 75010, France
ImClone Investigational Site
Paris, 75571, France
ImClone Investigational Site
Paris, 75651, France
ImClone Investigational Site
Rennes, 35033, France
ImClone Investigational Site
Saint-Jean, 31240, France
ImClone Investigational Site
Toulon Armées, 83800, France
ImClone Investigational Site
Berlin, 12200, Germany
ImClone Investigational Site
Essen, 45122, Germany
ImClone Investigational Site
Essen, 45136, Germany
ImClone Investigational Site
Frankfurt, 60487, Germany
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Gauting, 82131, Germany
ImClone Investigational Site
Großhansdorf, 22927, Germany
ImClone Investigational Site
Halle, 06120, Germany
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Hamburg, 21075, Germany
ImClone Investigational Site
Hamburg, 22087, Germany
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Heidelberg, 69126, Germany
ImClone Investigational Site
Hemer, 58675, Germany
ImClone Investigational Site
Hofheim, 65719, Germany
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Karlsruhe, 76137, Germany
ImClone Investigational Site
Lostau, 39291, Germany
ImClone Investigational Site
Löwenstein, 74245, Germany
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München, 81675, Germany
ImClone Investigational Site
Münster, 48149, Germany
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Regensburg, 93042, Germany
ImClone Investigational Site
Regensburg, 93049, Germany
ImClone Investigational Site
Ulm, 89081, Germany
ImClone Investigational Site
Athens, 11527, Greece
ImClone Investigational Site
Heraklion, Crete, 71110, Greece
ImClone Investigational Site
Pátrai, 26500, Greece
ImClone Investigational Site
Thessaloniki, 57010, Greece
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Budapest, 1125, Hungary
ImClone Investigational Site
Budapest, 1145, Hungary
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Deszk, 6772, Hungary
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Farkasgyepü, 8582, Hungary
ImClone Investigational Site
Mosonmagyaróvár, 9200, Hungary
ImClone Investigational Site
Székesfehérvár, 8000, Hungary
ImClone Investigational Site
Szombathely, 9700, Hungary
ImClone Investigational Site
Törökbálint, 2045, Hungary
ImClone Investigational Site
Lido di Camaiore, Lucca, 55041, Italy
ImClone Investigational Site
Aviano, Pordenone, 33081, Italy
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Frosinone, 03100, Italy
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Genova, 16132, Italy
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Milan, 20133, Italy
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Milan, 20162, Italy
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Monza, 20900, Italy
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Parma, 43100, Italy
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Perugia, 06126, Italy
ImClone Investigational Site
Cebu, 6000, Philippines
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Cebu City, 6000, Philippines
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Davao City, 8000, Philippines
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Makati City, 1229, Philippines
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Manila, 1000, Philippines
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Quezon City, 1000, Philippines
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Quezon City, 1102, Philippines
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Olsztyn, 10357, Poland
ImClone Investigational Site
Otwock, 05-400, Poland
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Poznan, 60-569, Poland
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Radom, 26-617, Poland
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Rzeszów, 35-055, Poland
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Szczecin, 70-891, Poland
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Torun, 87-100, Poland
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Wroclaw, 53-439, Poland
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Coimbra, 3041-801, Portugal
ImClone Investigational Site
Lisbon, 1099-023, Portugal
ImClone Investigational Site
Lisbon, 1649-035, Portugal
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Porto, 4200-072, Portugal
ImClone Investigational Site
Brasov, 500366, Romania
ImClone Investigational Site
Bucharest, 022328, Romania
ImClone Investigational Site
Bucharest, 030171, Romania
ImClone Investigational Site
Cluj-Napoca, 400015, Romania
ImClone Investigational Site
Craiova, Dolj, 200385, Romania
ImClone Investigational Site
Iași, 700106, Romania
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Piatra Neamţ, 610136, Romania
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Sibiu, 550245, Romania
ImClone Investigational Site
Ivanovo, 153013, Russia
ImClone Investigational Site
Kirov, 610021, Russia
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Krasnodar, 350040, Russia
ImClone Investigational Site
Moscow, 117997, Russia
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Omsk, 644013, Russia
ImClone Investigational Site
Saint Petersburg, 194044, Russia
ImClone Investigational Site
Saint Petersburg, 194291, Russia
ImClone Investigational Site
Saint Petersburg, 197022, Russia
ImClone Investigational Site
Saint Petersburg, 198255, Russia
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Smolensk, 214000, Russia
ImClone Investigational Site
Ufa, 450054, Russia
ImClone Investigational Site
Yaroslavl, 150054, Russia
ImClone Investigational Site
Belgrade, 11000, Serbia
ImClone Investigational Site
Kamenitz, 21204, Serbia
ImClone Investigational Site
Kragujevac, 34000, Serbia
ImClone Investigational Site
Niš, 18204, Serbia
ImClone Investigational Site
Singapore, 308433, Singapore
ImClone Investigational Site
Bratislava, 826 06, Slovakia
ImClone Investigational Site
Nitra, 949 88, Slovakia
ImClone Investigational Site
Poprad, 058 01, Slovakia
ImClone Investigational Site
Bloemfontein, Free State, 9301, South Africa
ImClone Investigational Site
Pretoria, Gauteng, 0002, South Africa
ImClone Investigational Site
Durban, KwaZulu-Natal, 4091, South Africa
ImClone Investigational Site
Incheon, 405760, South Korea
ImClone Investigational Site
Jeonju, 561712, South Korea
ImClone Investigational Site
Seongnam, 463-707, South Korea
ImClone Investigational Site
Seoul, 120752, South Korea
ImClone Investigational Site
Seoul, 135710, South Korea
ImClone Investigational Site
Seoul, 138736, South Korea
ImClone Investigational Site
Suwon, 442723, South Korea
ImClone Investigational Site
Seville, Andalusia, 41013, Spain
ImClone Investigational Site
Ávila, Castille and León, 05004, Spain
ImClone Investigational Site
Barcelona, Catalonia, 08035, Spain
ImClone Investigational Site
Barcelona, Catalonia, 08041, Spain
ImClone Investigational Site
Terrassa, Catalonia, 08221, Spain
ImClone Investigational Site
Madrid, Communidad de Madrid, 28041, Spain
ImClone Investigational Site
Madrid, Communidad de Madrid, 28050, Spain
ImClone Investigational Site
Majadahonda, Communidad de Madrid, 28222, Spain
ImClone Investigational Site
Barcelona, 08036, Spain
ImClone Investigational Site
L'Hospitalet de Llobregat, 08908, Spain
ImClone Investigational Site
Madrid, 28040, Spain
ImClone Investigational Site
Taichung, 40447, Taiwan
ImClone Investigational Site
Taichung, 40705, Taiwan
ImClone Investigational Site
Chiang Mai, 50002, Thailand
ImClone Investigational Site
Songkhla, 90110, Thailand
ImClone Investigational Site
Aberdeen, AB25 2ZN, United Kingdom
ImClone Investigational Site
Bournemouth, BH7 7DW, United Kingdom
ImClone Investigational Site
Dundee, DD1 9SY, United Kingdom
ImClone Investigational Site
Edinburgh, EH4 2XU, United Kingdom
ImClone Investigational Site
Guildford, GU2 7XX, United Kingdom
ImClone Investigational Site
Liverpool, L14 3PE, United Kingdom
ImClone Investigational Site
London, SW10 9NH, United Kingdom
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Manchester, M20 4BX, United Kingdom
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Manchester, M23 9LT, United Kingdom
ImClone Investigational Site
Preston, PR2 9HT, United Kingdom
Related Publications (4)
Ciuleanu T, Socinski MA, Obasaju C, Luft AV, Szczesna A, Szafranski W, Ramlau R, Balint B, Molinier O, Depenbrock H, Nanda S, Paz-Ares L, Thatcher N. Efficacy and Safety of Necitumumab Continuation Therapy in the Phase III SQUIRE Study of Patients With Stage IV Squamous Non-Small-Cell Lung Cancer. Clin Lung Cancer. 2018 Mar;19(2):130-138.e2. doi: 10.1016/j.cllc.2017.10.004. Epub 2017 Oct 13.
PMID: 29158123DERIVEDPaz-Ares L, Socinski MA, Shahidi J, Hozak RR, Soldatenkova V, Kurek R, Varella-Garcia M, Thatcher N, Hirsch FR. Correlation of EGFR-expression with safety and efficacy outcomes in SQUIRE: a randomized, multicenter, open-label, phase III study of gemcitabine-cisplatin plus necitumumab versus gemcitabine-cisplatin alone in the first-line treatment of patients with stage IV squamous non-small-cell lung cancer. Ann Oncol. 2016 Aug;27(8):1573-9. doi: 10.1093/annonc/mdw214. Epub 2016 May 20.
PMID: 27207107DERIVEDReck M, Socinski MA, Luft A, Szczesna A, Dediu M, Ramlau R, Losonczy G, Molinier O, Schumann C, Gralla RJ, Bonomi P, Brown J, Soldatenkova V, Chouaki N, Obasaju C, Peterson P, Thatcher N. The Effect of Necitumumab in Combination with Gemcitabine plus Cisplatin on Tolerability and on Quality of Life: Results from the Phase 3 SQUIRE Trial. J Thorac Oncol. 2016 Jun;11(6):808-18. doi: 10.1016/j.jtho.2016.03.002. Epub 2016 Mar 12.
PMID: 26980471DERIVEDThatcher N, Hirsch FR, Luft AV, Szczesna A, Ciuleanu TE, Dediu M, Ramlau R, Galiulin RK, Balint B, Losonczy G, Kazarnowicz A, Park K, Schumann C, Reck M, Depenbrock H, Nanda S, Kruljac-Letunic A, Kurek R, Paz-Ares L, Socinski MA; SQUIRE Investigators. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line therapy in patients with stage IV squamous non-small-cell lung cancer (SQUIRE): an open-label, randomised, controlled phase 3 trial. Lancet Oncol. 2015 Jul;16(7):763-74. doi: 10.1016/S1470-2045(15)00021-2. Epub 2015 Jun 1.
PMID: 26045340DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 18, 2009
First Posted
September 22, 2009
Study Start
January 7, 2010
Primary Completion
June 17, 2013
Study Completion
May 30, 2024
Last Updated
June 18, 2025
Results First Posted
June 27, 2016
Record last verified: 2025-05