Tivantinib Plus Erlotinib Versus Placebo Plus Erlotinib for the Treatment of Non-squamous, Non-small-cell Lung Cancer

A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study of ARQ197 Plus Erlotinib Versus Placebo Plus Erlotinib in Previously Treated Subjects With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer (NSCLC)

This study is to determine if the combination regimen of tivantinib with erlotinib will improve overall survival relative to erlotinib alone in subjects with locally advanced or metastatic non-squamous, non-small cell lung cancer who have received 1 or 2 prior systemic anti-cancer therapies.

Study Overview

• Status: Terminated
• Conditions: Non Squamous, Non-small-cell Lung Cancer
• Intervention / Treatment: Drug: Tivantinib; Drug: Erlotinib; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1048
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Buenos Aires, Argentina
  • Cordoba, Argentina, X5000AA1
  • San Miguel de Tucuman, Argentina
  • Tucuman, Argentina
  • Viedma, Argentina
  • Santa Fe
    • Rosario, Santa Fe, Argentina, S2000SDV
• Australia
  • Camperdown, Australia
  • Kogarah, Australia
  • Perth, Australia
  • St. Leonards, Australia, 2065
  • Wollongong, Australia
  • Woodville, Australia
  • Queensland
    • Greenslopes, Queensland, Australia, 4120
• Austria
  • Salzburg, Austria, 5020
  • Wels, Austria, A-4600
• Belgium
  • Brasschaat, Belgium, 2930
  • Brussels, Belgium
  • Duffel, Belgium, 2570
• Brazil
  • Ijui, Brazil
  • Porto Alegre, Brazil
  • Sao Paulo, Brazil
  • Sao Paulo, Brazil, 01224-10
  • BA
    • Salvador, BA, Brazil, 41253-190
  • RJ
    • Rio de Janeiro, RJ, Brazil, 20231-050
  • RS
    • Passo Fundo, RS, Brazil, 99010-080
    • Passo Fundo, RS, Brazil, 99010-260
    • Porto Alegre, RS, Brazil, 90430-090
  • SC
    • Joinville, SC, Brazil, 89202050
  • Santa Catarina
    • Joinville, Santa Catarina, Brazil, 89202
• Canada
  • Montreal, Canada, H2W 1S6
  • Quebec, Canada, G1V 4G5
  • Toronto, Canada, M5G 2M9
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
  • British Columbia
    • Surrey, British Columbia, Canada, V3V 1Z2
    • Victoria, British Columbia, Canada, V8R lC3
  • Manitoba
    • Winnipeg, Manitoba, Canada, RSE 0V9
  • Ontario
    • London, Ontario, Canada, N6A 4L6
    • Thunder Bay, Ontario, Canada, P7B6V4
    • Toronto, Ontario, Canada, M5G 1X5
  • Quebec
    • Montreal, Quebec, Canada, H1T 2M4
• Chile
  • Santiago, Chile, 7500710
  • Santiago, Chile, 7500921
  • Santiago, Chile, 7520378
  • Santiago, Chile, 8380455
• Czechia
  • Ostrava, Czechia, 70384
  • Pardubice, Czechia, 53203
  • Praha, Czechia, 12808
  • Usti nad Labem, Czechia
• Denmark
  • Herlev, Denmark, DK-2730
  • Naestved, Denmark, 4700
  • Odense, Denmark, DK-5000
• France
  • Besancon, France, 25000
  • Brest, France, 29609
  • Caen Cedex, France, 14033
  • Grenoble, France, 9
  • Lille, France, 59037
  • Marseille Cedex, France
  • Paris, France, 75013
  • Paris Cedex, France, 75230
  • Pierre Benite, France, 69495
  • Rennes Cedex, France, 35033
  • Saint-Priest en Jarez, France
  • Strasbourg Cedex, France
  • Toulouse Cedex, France, 31059
  • Tours Cedex, France, 37044
  • Villejuif, France, 94805
• Germany
  • Bad Berka, Germany, 99437
  • Berlin, Germany, 10117
  • Berlin, Germany, 12203
  • Erfurt, Germany
  • Essen, Germany, 45122
  • Esslingen, Germany, 73730
  • Gauting, Germany, 82131
  • Großhansdorf, Germany, 22927
  • Halle, Germany, 06120
  • Hamburg, Germany, 21075
  • Hannover, Germany, 30625
  • Karlsruhe, Germany, 76137
  • Kassel, Germany, 34125
  • Koln, Germany, 51109
  • Leverkusen, Germany, 51375
  • Lowenstein, Germany, 74245
  • Mainz, Germany, 55131
  • Mannheim, Germany, 68167
  • Munchen, Germany, 80336
  • Munchen, Germany
  • Munchen, Germany, 81925
  • Porta Westfalica, Germany, 32457
  • Rheine, Germany, 48431
  • Villingen-Schwenningen, Germany, 78050
• Hungary
  • Deszk, Hungary, H-6772
  • Gyula, Hungary, H-5703
  • Matrahaza, Hungary, H-3233
  • Szekesfehervar, Hungary, H-8000
  • Szolnok, Hungary, H-5000
• Italy
  • Ancona, Italy
  • Avellino, Italy, 83100
  • Aviano, Italy, 33081
  • Bari, Italy, 70124
  • Catania, Italy, 95126
  • Cremona, Italy, 26100
  • Cuneo, Italy, 12100
  • Firenze, Italy, 50134
  • Livorno, Italy, 57100
  • Milano, Italy, 20162
  • Modena, Italy, 41124
  • Monza, Italy, 20900
  • Napoli, Italy, 80131
  • Novara, Italy, 28100
  • Orbassano, Italy, 10043
  • Padova, Italy, 35128
  • Palermo, Italy, 90146
  • Parma, Italy, 43126
  • Perugia, Italy, 06132
  • Roma, Italy, 00152
  • Rozzano, Italy, 20089
  • Sassari, Italy, 07100
  • Sondalo, Italy, 23035
  • Sora, Italy, 03039
  • Torino, Italy
• Mexico
  • Guadalajara, Mexico, 44280
  • Mexico City, Mexico
  • Oaxaca, Mexico, 68000
  • Oaxaca, Mexico, 70000
  • DF
    • Mexico, DF, Mexico
  • Nuevo Leon
    • Monterrey, Nuevo Leon, Mexico, 64460
• Netherlands
  • Amsterdam, Netherlands
  • ER
    • Enschede, ER, Netherlands, 7513
  • HA
    • Helmond, HA, Netherlands, 5707
• Peru
  • Arequipa, Peru
  • Lima, Peru
  • Lima, Peru, 27
  • Lima, Peru, 34
  • Lima, Peru, 41
• Poland
  • Bystra, Poland, 43-360
  • Krakow, Poland, 31302
  • Lublin, Poland
  • Olsztyn, Poland, 31302
  • Opole, Poland
  • Poznan, Poland
  • Poznan, Poland, 60-569
  • Prabuty, Poland, 82550
  • Rzeszow, Poland, 35922
  • Szczecin, Poland, 70891
  • Torun, Poland
  • Walbrzych, Poland
• Romania
  • Cluj-Napoca, Romania, 400015
  • Craiova, Romania, 200385
  • Oradea, Romania, 410167
• Russian Federation
  • Chelyabinsk, Russian Federation, 454087
  • Irkutsk, Russian Federation, 664035
  • Izhevsk, Russian Federation, 426009
  • Kursk, Russian Federation, 305035
  • Moscow, Russian Federation, 125367
  • Moscow, Russian Federation, 115478
  • Novgorod, Russian Federation, 603081
  • Novosibirsk, Russian Federation
  • Pyatigorsk, Russian Federation, 357502
  • St Petersburg, Russian Federation, 197758
  • St Petersburg, Russian Federation, 198255
  • St. Petersburg, Russian Federation, 197022
  • Tula, Russian Federation, 300040
  • Tyumen, Russian Federation, 625041
• Spain
  • Alicante, Spain, 03010
  • Barcelona, Spain, 08003
  • Barcelona, Spain, 08907
  • Coruna, Spain, 15006
  • Coruna, Spain, 15009
  • La Laguna, Spain, 38320
  • Madrid, Spain
  • Madrid, Spain, 28034
  • Madrid, Spain, 28041
  • Malaga, Spain, 29010
  • Manresa, Spain, 08243
  • Oviedo, Spain, 33006
  • Palma de Mallorca, Spain, 07010
  • Sabadell, Spain, 08208
  • Santiago de Compostela, Spain, 15706
  • Sevilla, Spain, 41013
  • Sevilla, Spain, 41700
  • Valencia, Spain, 46010
  • Zaragoza, Spain, 50009
  • Bilbao
    • Barakaldo, Bilbao, Spain, 48903
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36204
• Sweden
  • Linkoping, Sweden, 581 85
  • Lund, Sweden
• United Kingdom
  • Aberdeen, United Kingdom, AB25 2ZN
  • Glasgow, United Kingdom, G12OYN
  • London, United Kingdom, NW1 2PG
  • London, United Kingdom, W6 9RF
  • Manchester, United Kingdom, M20 4BX
  • Nottingham, United Kingdom, NG5 1PB
  • Sheffield, United Kingdom, S10 2SJ
  • Surrey
    • Guildford, Surrey, United Kingdom, GU2 7XX
• United States
  • Arizona
    • Tucson, Arizona, United States, 85704
    • Tucson, Arizona, United States, 85715
    • Tucson, Arizona, United States, 85710
    • Tucson, Arizona, United States, 85724-5024
  • California
    • Los Angeles, California, United States, 90048
    • Oxnard, California, United States
    • Rancho Mirage, California, United States, 39800
    • Rancho Mirage, California, United States, 92270
    • Santa Monica, California, United States, 90404
  • Colorado
    • Aurora, Colorado, United States, 80012
    • Boulder, Colorado, United States, 80303
    • Colorado Springs, Colorado, United States, 80909
    • Colorado Springs, Colorado, United States, 80907
    • Denver, Colorado, United States, 80218
    • Denver, Colorado, United States, 80220
    • Lakewood, Colorado, United States, 80228
    • Littleton, Colorado, United States, 80120
    • Lone Tree, Colorado, United States, 80124
    • Longmont, Colorado, United States, 80501
    • Parker, Colorado, United States, 80138
    • Thornton, Colorado, United States, 80260
  • Delaware
    • Newark, Delaware, United States, 19713
  • Florida
    • Fort Myers, Florida, United States, 33916
    • Miami Beach, Florida, United States, 33012
    • Pensacola, Florida, United States, 32504
  • Georgia
    • Atlanta, Georgia, United States, 30341
    • Austell, Georgia, United States, 30106
    • Carrollton, Georgia, United States, 30117
    • Cartersville, Georgia, United States, 30121
    • Douglasville, Georgia, United States, 30134
    • Marietta, Georgia, United States, 30060
  • Illinois
    • Chicago, Illinois, United States, 60637
  • Indiana
    • Carmel, Indiana, United States, 46032
    • Fishers, Indiana, United States, 46037
    • Goshen, Indiana, United States, 46526
    • Greenfield, Indiana, United States, 46140
    • Indianapolis, Indiana, United States, 46219
    • Indianapolis, Indiana, United States, 46227
    • Indianapolis, Indiana, United States, 48202
  • Kentucky
    • Lexington, Kentucky, United States
    • Louisville, Kentucky, United States
  • Maryland
    • Towson, Maryland, United States, 21204
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
  • Missouri
    • Saint Louis, Missouri, United States, 63110
  • Nebraska
    • Grand Island, Nebraska, United States, 68803
    • Omaha, Nebraska, United States, 68198
  • Nevada
    • Henderson, Nevada, United States, 89052
    • Henderson, Nevada, United States, 89074
    • Las Vegas, Nevada, United States, 89169
    • Las Vegas, Nevada, United States, 89128
    • Las Vegas, Nevada, United States, 89148
  • New Jersey
    • East Orange, New Jersey, United States, 07018
  • New Mexico
    • Albuquerque, New Mexico, United States, 87131
  • New York
    • Bronx, New York, United States, 10467
    • Buffalo, New York, United States, 14263
    • Goshen, New York, United States, 10924
    • Latham, New York, United States
    • New York, New York, United States, 10032
  • Ohio
    • Cincinnati, Ohio, United States, 45242
    • Cleveland, Ohio, United States, 44195
    • Kettering, Ohio, United States
  • Oregon
    • Eugene, Oregon, United States, 97401
    • Portland, Oregon, United States, 97239
    • Portland, Oregon, United States, 97225
    • Portland, Oregon, United States, 97213
    • Portland, Oregon, United States, 97227
    • Springfield, Oregon, United States, 97477
    • Tualatin, Oregon, United States, 97062
  • Pennsylvania
    • Harrisburg, Pennsylvania, United States, 17109
    • Hershey, Pennsylvania, United States, 17033-0850
    • Philadelphia, Pennsylvania, United States, 19104
  • South Carolina
    • Columbia, South Carolina, United States, 29120
    • Easley, South Carolina, United States, 29640
    • Greenville, South Carolina, United States, 29605
    • Greenville, South Carolina, United States, 29601
    • Greenville, South Carolina, United States, 29615
    • Spartanburg, South Carolina, United States, 29307
  • Tennessee
    • Bartlett, Tennessee, United States, 38138
    • Chattanooga, Tennessee, United States, 37404
    • Germantown, Tennessee, United States, 38138
    • Knoxville, Tennessee, United States, 37909
    • Memphis, Tennessee, United States, 38104
    • Nashville, Tennessee, United States, 37203
    • Southaven, Tennessee, United States, 38671
  • Texas
    • Austin, Texas, United States, 78705
    • Austin, Texas, United States, 78731
    • Austin, Texas, United States, 78745
    • Austin, Texas, United States, 78758
    • Cedar Park, Texas, United States, 78731
    • Dallas, Texas, United States, 75246
    • Dallas, Texas, United States, 75216-9982
    • Fort Worth, Texas, United States, 76104
    • Fort Worth, Texas, United States, 76132
    • Kyle, Texas, United States, 78640
    • Round Rock, Texas, United States, 78681
    • Round Rock, Texas, United States, 78665
    • San Marcos, Texas, United States, 78666
  • Utah
    • Salt Lake City, Utah, United States, 84112
  • Virginia
    • Arlington, Virginia, United States, 22205
    • Fairfax, Virginia, United States, 22031
    • Gainesville, Virginia, United States, 20155
    • Leesburg, Virginia, United States, 20176
    • Midlothian, Virginia, United States, 23112
    • Richmond, Virginia, United States, 23298
    • Winchester, Virginia, United States, 22601
    • Woodbridge, Virginia, United States, 22191
  • Washington
    • Seattle, Washington, United States, 98104
    • Vancouver, Washington, United States, 98684
    • Vancouver, Washington, United States, 98686
    • Yakima, Washington, United States, 98902

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Histologically or cytologically confirmed surgically unresectable locally advanced or metastatic (stage IIIB/IV) non-squamous non-small-cell lung cancer.
• Measurable disease and documented disease progression following last prior therapy according to Response Evaluation Criteria in Solid Tumors (RECIST) criteria, Version 1.1.
• Have received one or two prior lines of systemic anti-cancer therapy therapy for advanced or metastatic disease, one of which must be a platinum-doublet therapy. Patients who received only adjuvant treatment will be eligible only if disease progression occurred <6 months after completion of adjuvant therapy. Prior maintenance therapy is allowed and will be considered as the same line of therapy when continued without discontinuation after initiation of a treatment regimen.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
• Resolution of any toxic effects of prior therapy (including radiotherapy) according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE), Version 4.0, Grade ≤1 (with the exception of alopecia and ≤grade 2 neuropathy). Subject must have recovered from significant surgery-related complications.
• Demonstrate adequate bone marrow, liver, and renal functions, defined as:
• ALT, AST, and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN) in subjects with no liver metastasis and ≤5.0 x ULN in subjects with liver metastasis.
• Total bilirubin ≤ 1.5 × ULN (≤ 4 × ULN total and ≤1.5 × ULN direct bilirubin is acceptable for subjects with Gilbert's syndrome).
• ANC ≥1.5 × 10^9/L.
• Platelet count ≥100 × 10^9/L.
• Hemoglobin ≥9.0 g/dL (transfusion and/or growth factor support allowed).
• Serum creatinine ≤1.5 × ULN or creatinine clearance ≥ 60 mL/min.
• Archival and/or fresh biopsy tissue sample must be available for biomarker determination. The status of the following biomarkers will be collected in this study: EGFR and KRAS mutation status prior to randomization, and MET status post randomization
• If of child-bearing/reproductive potential (female or male), must agree to use double-barrier contraceptive measures, oral contraception, or avoidance of intercourse during the study and for 90 days after last investigational drug dose received
• If female and of childbearing potential, must have a negative result of a pregnancy test (serum or urine) within 72 hours prior to initiating study treatment.
• Must have signed and dated an approved Informed Consent Form (Including HIPAA authorization, if applicable) before performance of any study-specific procedures or tests. Subjects must be fully informed about their illness and the investigational nature of the study protocol (including forseeable risks and possible side effects)

Exclusion Criteria:

• Prior therapy with an EGFR inhibitor and/or ARQ 197 (or other known c-MET inhibitor).
• Receipt of any systemic anti-tumor treatment for NSCLC within 3 weeks prior to randomization.
• Receipt of palliative radiotherapy within 2 weeks or radiotherapy for curative intent of target lesions within 3 weeks prior to randomization. Lesions subjected to radiotherapy within 3 weeks prior to randomization may not be used as target lesions.
• Major surgical procedure within 3 weeks prior to randomization.
• History of cardiac disease:

Congestive heart failure defined as Class II to IV per New York Heart Association classification; active coronary artery disease; previously diagnosed symptomatic bradycardia (subjects with asymptomatic bradycardia and heart rate above 50 bpm are allowed) or other cardiac arrhythmia defined as ≥Grade 2 according to NCI CTCAE, version 4.0, or uncontrolled hypertension; myocardial infarction that occurred within 6 months prior to study entry (myocardial infarction that occurred > 6 months prior to study entry is permitted).

• Clinically unstable central nervous system (CNS) metastasis (to be enrolled in the study, subjects must have confirmation of stable disease by MRI or computed tomography (CT) scan within 4 weeks of randomization and have CNS metastases well controlled by steroids, anti-epileptics or other symptom-relieving medications).
• Need to breastfeed a child during or within 12 weeks of completing the study.
• Significant gastrointestinal disorder that, in the opinion of the investigator, could interfere with absorption of ARQ 197 and/or erlotinib (eg, Crohn's disease, small or large bowel resection, malabsorption syndrome).
• Inability or unwillingness to swallow the complete doses of ARQ 197 or erlotinib.
• Any known contraindication to treatment with, including hypersensitivity to, ARQ 197 or erlotinib.
• History of malignancy other than NSCLC within the 5 years prior to randomization, with the exceptions of adequately treated intraepithelial carcinoma of the cervix uteri; prostate carcinoma with a prostate-specific antigen value <0.2 ng/mL; or basal or squamous-cell carcinoma of the skin.
• Known infection with human immunodeficiency virus (HIV), hepatitis B virus (HBV) or hepatitis C virus (HCV).
• Any other significant co-morbid condition that, in opinion of the investigator, would impair study participation or cooperation.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Tivantinib and erlotinib; Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day	Drug: Tivantinib; Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day; Other Names: ARQ197; Drug: Erlotinib; Erlotinib 150 mg oral tablets, given once a day
Active Comparator: Placebo and erlotinib; Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day	Drug: Erlotinib; Erlotinib 150 mg oral tablets, given once a day; Drug: Placebo; Tivantinib Placebo tablets given twice a day; Other Names: No drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer	The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.	Date of randomization up to date of death, up to approximately 1 year 11 months postdose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-free Survival Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer	Progression-free Survival (PFS) was defined as the time from the date of randomization to the date of the first objective documentation of disease progression or date of death from any cause (whichever comes first). As per the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, progression was defined as at least a 20% increase in the sum of diameters of target lesions.	Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Overall Survival in the Epidermal Growth Factor Receptor Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC	The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause.	Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Progression-free Survival in the Epidermal Growth Factor Receptor (EGFR) Gene Wild-Type Subpopulation Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants Non-Squamous NSCLC	Progression-free Survival (PFS) was defined as the time from the date of randomization to the date of the first objective documentation of disease progression or date of death from any cause (whichever comes first). As per the Response Evaluation Criteria in Solid Tumors, Version 1.1 (RECIST v1.1) criteria, progression was defined as at least a 20% increase in the sum of diameters of target lesions.	Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Best Overall Tumor Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer	The best overall response was defined as the best response (in the order of confirmed complete response [CR], confirmed partial response [PR], stable disease [SD], and progressive disease [PD]) among all overall responses recorded from the start of treatment until the participant withdrew from the study. If there was no tumor assessment after the first dose of study drug, the best overall response was classified as Inevaluable. Based on RECIST v1.1, CR was defined as a disappearance of all target lesions, PR was defined as at least a 30% decrease in the sum of diameters of target lesions, and SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease (PD; at least a 20% increase in the sum of diameters of target lesions.	From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose
Duration of Response Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Locally Advanced or Metastatic, Non-Squamous, Non-Small-Cell Lung Cancer	Duration of response was defined for participants with confirmed CR or PR as the time from the date of the first documentation of objective response (CR or PR) to the date of the first documentation of progressive disease. Duration of SD was defined for participants whose best response was SD as the time from the randomization date to the date of the first documentation of progressive disease.	From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Reported in ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous, Non-Small-Cell Lung Cancer	Treatment-emergent AEs (TEAEs) were defined as those AEs that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.	Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Treatment-Emergent Adverse Events Related to Tivantinib/Placebo Experienced by ≥5% of Participants Following Treatment With Tivantinib (ARQ 197) Plus Erlotinib Compared to Placebo Plus Erlotinib in Previously Treated Participants With Non-Squamous NSCLC	Treatment-emergent AEs (TEAEs) were defined as those AEs that occurred, having been absent before the study, or worsened in severity after the initiation of study treatment administration.	Baseline up to 30 days after last dose, up to 1 year 11 months postdose

Collaborators and Investigators

• Sponsor: Daiichi Sankyo, Inc.
• Collaborators: ArQule, Inc. (a wholly owned subsidiary of Merck Sharp and Dohme, a subsidiary of Merck & Co., Inc.)

Publications and helpful links

General Publications

• Scagliotti G, von Pawel J, Novello S, Ramlau R, Favaretto A, Barlesi F, Akerley W, Orlov S, Santoro A, Spigel D, Hirsh V, Shepherd FA, Sequist LV, Sandler A, Ross JS, Wang Q, von Roemeling R, Shuster D, Schwartz B. Phase III Multinational, Randomized, Double-Blind, Placebo-Controlled Study of Tivantinib (ARQ 197) Plus Erlotinib Versus Erlotinib Alone in Previously Treated Patients With Locally Advanced or Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2015 Aug 20;33(24):2667-74. doi: 10.1200/JCO.2014.60.7317. Epub 2015 Jul 13.
• Scagliotti GV, Novello S, Schiller JH, Hirsh V, Sequist LV, Soria JC, von Pawel J, Schwartz B, Von Roemeling R, Sandler AB. Rationale and design of MARQUEE: a phase III, randomized, double-blind study of tivantinib plus erlotinib versus placebo plus erlotinib in previously treated patients with locally advanced or metastatic, nonsquamous, non-small-cell lung cancer. Clin Lung Cancer. 2012 Sep;13(5):391-5. doi: 10.1016/j.cllc.2012.01.003. Epub 2012 Mar 21.

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2011
• Primary Completion (Actual): December 15, 2012
• Study Completion (Actual): December 15, 2012

Study Registration Dates

• First Submitted: November 17, 2010
• First Submitted That Met QC Criteria: November 18, 2010
• First Posted (Estimate): November 19, 2010

Study Record Updates

• Last Update Posted (Actual): April 6, 2021
• Last Update Submitted That Met QC Criteria: March 12, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Non squamous, non-small-cell lung cancer; Epidermal growth factor receptor; c-Met inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Protein Kinase Inhibitors; Erlotinib Hydrochloride
• Other Study ID Numbers: ARQ197-A-U302; 2010-022365-10 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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