Non Squamous, Non-small-cell Lung Cancer
Conditions
Keywords
Non squamous, non-small-cell lung cancer, Epidermal growth factor receptor, c-Met inhibitor
Brief summary
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.
Interventions
DRUGTivantinib
Tivantinib 720 mg daily as 3 x 120 mg oral tablets given twice a day
DRUGPlacebo
Tivantinib Placebo tablets given twice a day
DRUGErlotinib
Erlotinib 150 mg oral tablets, given once a day
Sponsors
ArQule, Inc., a subsidiary of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc. (Rahway, NJ USA)
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Date of randomization up to date of death, up to approximately 1 year 11 months postdose | The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 | Date of randomization up to date of death, up to approximately 1 year 11 months postdose | The overall survival (OS) was defined as the time from the date of randomization to the date of death from any cause. |
| 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 | Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose | 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. |
| 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 | From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose | 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. |
| 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 | Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose | 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. |
| 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 | Baseline up to 30 days after last dose, up to 1 year 11 months postdose | 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. |
| 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 | Baseline up to 30 days after last dose, up to 1 year 11 months postdose | 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. |
| 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 | From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose | 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. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Canada, Chile, Czechia, Denmark, France, Germany, Hungary, Italy, Mexico, Netherlands, Peru, Poland, Romania, Russia, Spain, Sweden, United Kingdom, United States
Participant flow
Recruitment details
A total of 1048 participants who met all inclusion criteria and no exclusion criteria were enrolled between 11 Jan 2011 and 18 Jul 2012 at 140 sites in Europe, 78 sites in United States, 32 sites in Latin America, and 20 sites in Canada/Australia. Of the 1048 participants, a total of 1037 participants received treatment.
Pre-assignment details
Participants were to be randomized in a 1:1 ratio to tivantinib at 360 mg BID (total daily dose, 720 mg) + erlotinib at 150 mg QD, or placebo BID + erlotinib at 150 mg QD, to be administered in a double-blinded manner.
Participants by arm
| Arm | Count |
|---|---|
| Tivantinib and Erlotinib Participants who were randomized to receive Tivantinib 720 mg daily (360 mg twice a day) in combination with 150 mg of erlotinib, given once a day. | 526 |
| Placebo and Erlotinib Participants who were randomized to receive Tivantinib placebo given twice a day in combination with 150 mg of erlotinib, given once a day. | 522 |
| Total | 1,048 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 65 | 48 |
| Overall Study | Clinical disease progression | 54 | 36 |
| Overall Study | Death | 22 | 29 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | 'Missing' or 'Terminated by sponsor' | 12 | 8 |
| Overall Study | Progressive disease | 295 | 350 |
| Overall Study | Protocol Violation | 1 | 2 |
| Overall Study | Withdrawal by Subject | 31 | 23 |
Baseline characteristics
| Characteristic | Tivantinib and Erlotinib | Placebo and Erlotinib | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 206 Participants | 196 Participants | 402 Participants |
| Age, Categorical Between 18 and 65 years | 320 Participants | 326 Participants | 646 Participants |
| Age, Continuous | 61.2 years STANDARD_DEVIATION 10.1 | 61.1 years STANDARD_DEVIATION 9.84 | 61.1 years STANDARD_DEVIATION 9.96 |
| Sex: Female, Male Female | 216 Participants | 213 Participants | 429 Participants |
| Sex: Female, Male Male | 310 Participants | 309 Participants | 619 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 77 / 520 | 65 / 517 |
| other Total, other adverse events | 513 / 520 | 503 / 517 |
| serious Total, serious adverse events | 219 / 520 | 191 / 517 |
Outcome results
Primary
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.
Time frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Population: Overall survival was assessed in the Intent-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib and Erlotinib | 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 | 8.5 months |
| Placebo and Erlotinib | 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 | 7.8 months |
p-value: 0.808695% CI: [0.841, 1.149]Log Rank
Secondary
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.
Time frame: From baseline up to disease progression or the development of unacceptable toxicity (whichever occurs first), up to 1 year 11 months postdose
Population: Best overall response was assessed in the Intent-to-treat population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivantinib and Erlotinib | 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 | Objective response (CR+PR) | 54 Participants |
| Tivantinib and Erlotinib | 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 | Progressive disease (PD) | 189 Participants |
| Tivantinib and Erlotinib | 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 | Partial response (PR) | 53 Participants |
| Tivantinib and Erlotinib | 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 | Best response of SD or better | 241 Participants |
| Tivantinib and Erlotinib | 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 | Stable disease (SD) | 187 Participants |
| Tivantinib and Erlotinib | 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 | Inevaluable | 96 Participants |
| Tivantinib and Erlotinib | 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 | Complete response (CR) | 1 Participants |
| Placebo and Erlotinib | 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 | Inevaluable | 90 Participants |
| Placebo and Erlotinib | 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 | Complete response (CR) | 1 Participants |
| Placebo and Erlotinib | 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 | Partial response (PR) | 33 Participants |
| Placebo and Erlotinib | 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 | Objective response (CR+PR) | 34 Participants |
| Placebo and Erlotinib | 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 | Stable disease (SD) | 133 Participants |
| Placebo and Erlotinib | 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 | Progressive disease (PD) | 265 Participants |
| Placebo and Erlotinib | 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 | Best response of SD or better | 167 Participants |
Secondary
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.
Time frame: From the date of first objective response (CR or PR) or SD to date of progressive disease, up to 1 year 11 months postdose
Population: Duration of response was assessed in the Intent-to-treat population.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Tivantinib and Erlotinib | 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 objective response (CR or PR) | 40.43 weeks |
| Tivantinib and Erlotinib | 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 SD | 28.29 weeks |
| Placebo and Erlotinib | 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 objective response (CR or PR) | 47.86 weeks |
| Placebo and Erlotinib | 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 SD | 23.86 weeks |
Secondary
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.
Time frame: Date of randomization up to date of death, up to approximately 1 year 11 months postdose
Population: Overall survival was assessed in participants with the epidermal growth factor receptor wild-type gene.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib and Erlotinib | 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 | 7.2 months |
| Placebo and Erlotinib | 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 | 7.1 months |
Secondary
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.
Time frame: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Population: Progression-free survival (PFS) was assessed in the Intent-to-treat population.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib and Erlotinib | 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 | 3.6 months |
| Placebo and Erlotinib | 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 | 1.9 months |
Secondary
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.
Time frame: Date of randomization to disease progression or death (whichever comes first), up to 1 year 11 months postdose
Population: Progression-free survival (PFS) was assessed in participants with the epidermal growth factor receptor wild-type gene.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Tivantinib and Erlotinib | 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 | 2.7 months |
| Placebo and Erlotinib | 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 | 1.9 months |
Secondary
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.
Time frame: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Population: Adverse events were assessed in the Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivantinib and Erlotinib | 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 | TEAE related to tivantinib/placebo | 324 Participants |
| Tivantinib and Erlotinib | 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 | General Disorders & Administration Site Conditions | 135 Participants |
| Tivantinib and Erlotinib | 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 | Gastrointestinal Disorders | 165 Participants |
| Tivantinib and Erlotinib | 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 | Asthenia | 43 Participants |
| Tivantinib and Erlotinib | 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 | Anemia | 44 Participants |
| Tivantinib and Erlotinib | 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 | Fatigue | 78 Participants |
| Tivantinib and Erlotinib | 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 | Diarrhea | 81 Participants |
| Tivantinib and Erlotinib | 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 | Metabolism and Nutrition Disorders | 82 Participants |
| Tivantinib and Erlotinib | 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 | Blood and Lymphatic System Disorders | 87 Participants |
| Tivantinib and Erlotinib | 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 | Decreased appetite | 73 Participants |
| Tivantinib and Erlotinib | 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 | Nausea | 63 Participants |
| Tivantinib and Erlotinib | 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 | Skin and Subcutaneous Tissue Disorders | 148 Participants |
| Tivantinib and Erlotinib | 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 | Neutropenia | 54 Participants |
| Tivantinib and Erlotinib | 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 | Dermatitis acneiform | 26 Participants |
| Tivantinib and Erlotinib | 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 | Vomiting | 31 Participants |
| Tivantinib and Erlotinib | 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 | Rash | 61 Participants |
| Placebo and Erlotinib | 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 | Rash | 71 Participants |
| Placebo and Erlotinib | 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 | TEAE related to tivantinib/placebo | 301 Participants |
| Placebo and Erlotinib | 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 | Blood and Lymphatic System Disorders | 27 Participants |
| Placebo and Erlotinib | 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 | Anemia | 17 Participants |
| Placebo and Erlotinib | 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 | Neutropenia | 5 Participants |
| Placebo and Erlotinib | 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 | Gastrointestinal Disorders | 163 Participants |
| Placebo and Erlotinib | 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 | Diarrhea | 96 Participants |
| Placebo and Erlotinib | 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 | Nausea | 68 Participants |
| Placebo and Erlotinib | 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 | Vomiting | 39 Participants |
| Placebo and Erlotinib | 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 | General Disorders & Administration Site Conditions | 114 Participants |
| Placebo and Erlotinib | 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 | Asthenia | 38 Participants |
| Placebo and Erlotinib | 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 | Fatigue | 63 Participants |
| Placebo and Erlotinib | 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 | Metabolism and Nutrition Disorders | 84 Participants |
| Placebo and Erlotinib | 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 | Decreased appetite | 71 Participants |
| Placebo and Erlotinib | 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 | Skin and Subcutaneous Tissue Disorders | 130 Participants |
| Placebo and Erlotinib | 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 | Dermatitis acneiform | 27 Participants |
Secondary
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.
Time frame: Baseline up to 30 days after last dose, up to 1 year 11 months postdose
Population: Adverse events were assessed in the Safety population.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Tivantinib and Erlotinib | 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 | Asthenia | 100 Participants |
| Tivantinib and Erlotinib | 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 | Diarrhea | 180 Participants |
| Tivantinib and Erlotinib | 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 | Rash | 172 Participants |
| Tivantinib and Erlotinib | 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 | Decreased appetite | 151 Participants |
| Tivantinib and Erlotinib | 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 | Dyspnea | 136 Participants |
| Tivantinib and Erlotinib | 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 | Fatigue | 136 Participants |
| Tivantinib and Erlotinib | 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 | Nausea | 121 Participants |
| Tivantinib and Erlotinib | 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 | Cough | 110 Participants |
| Tivantinib and Erlotinib | 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 | Any TEAE | 513 Participants |
| Tivantinib and Erlotinib | 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 | Dermatitis acneiform | 90 Participants |
| Tivantinib and Erlotinib | 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 | Vomiting | 73 Participants |
| Tivantinib and Erlotinib | 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 | Anemia | 83 Participants |
| Tivantinib and Erlotinib | 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 | Weight decreased | 57 Participants |
| Tivantinib and Erlotinib | 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 | Constipation | 57 Participants |
| Tivantinib and Erlotinib | 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 | Pyrexia | 60 Participants |
| Tivantinib and Erlotinib | 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 | Back pain | 54 Participants |
| Tivantinib and Erlotinib | 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 | Dry skin | 41 Participants |
| Tivantinib and Erlotinib | 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 | Pruritus | 31 Participants |
| Tivantinib and Erlotinib | 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 | Neutropenia | 62 Participants |
| Tivantinib and Erlotinib | 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 | Headache | 41 Participants |
| Tivantinib and Erlotinib | 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 | Edema, peripheral | 37 Participants |
| Tivantinib and Erlotinib | 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 | Insomnia | 33 Participants |
| Tivantinib and Erlotinib | 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 | Abdominal pain | 34 Participants |
| Tivantinib and Erlotinib | 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 | Noncardiac chest pain | 34 Participants |
| Tivantinib and Erlotinib | 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 | Pneumonia | 35 Participants |
| Tivantinib and Erlotinib | 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 | Dyspepsia | 30 Participants |
| Tivantinib and Erlotinib | 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 | Abdominal pain, upper | 33 Participants |
| Tivantinib and Erlotinib | 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 | Mucosal inflammation | 27 Participants |
| Tivantinib and Erlotinib | 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 | Stomatitis | 22 Participants |
| Tivantinib and Erlotinib | 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 | Hemoptysis | 30 Participants |
| Tivantinib and Erlotinib | 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 | General physical health deterioration | 29 Participants |
| Tivantinib and Erlotinib | 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 | Pain in extremity | 28 Participants |
| Tivantinib and Erlotinib | 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 | Dizziness | 26 Participants |
| Tivantinib and Erlotinib | 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 | Alopecia | 26 Participants |
| Placebo and Erlotinib | 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 | Dyspepsia | 24 Participants |
| Placebo and Erlotinib | 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 | Any TEAE | 503 Participants |
| Placebo and Erlotinib | 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 | Pruritus | 44 Participants |
| Placebo and Erlotinib | 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 | Diarrhea | 212 Participants |
| Placebo and Erlotinib | 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 | Alopecia | 14 Participants |
| Placebo and Erlotinib | 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 | Rash | 193 Participants |
| Placebo and Erlotinib | 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 | Neutropenia | 10 Participants |
| Placebo and Erlotinib | 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 | Decreased appetite | 149 Participants |
| Placebo and Erlotinib | 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 | Abdominal pain, upper | 19 Participants |
| Placebo and Erlotinib | 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 | Dyspnea | 117 Participants |
| Placebo and Erlotinib | 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 | Headache | 28 Participants |
| Placebo and Erlotinib | 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 | Fatigue | 113 Participants |
| Placebo and Erlotinib | 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 | General physical health deterioration | 18 Participants |
| Placebo and Erlotinib | 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 | Nausea | 123 Participants |
| Placebo and Erlotinib | 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 | Edema, peripheral | 29 Participants |
| Placebo and Erlotinib | 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 | Cough | 91 Participants |
| Placebo and Erlotinib | 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 | Mucosal inflammation | 24 Participants |
| Placebo and Erlotinib | 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 | Asthenia | 90 Participants |
| Placebo and Erlotinib | 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 | Insomnia | 29 Participants |
| Placebo and Erlotinib | 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 | Dermatitis acneiform | 98 Participants |
| Placebo and Erlotinib | 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 | Dizziness | 16 Participants |
| Placebo and Erlotinib | 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 | Vomiting | 81 Participants |
| Placebo and Erlotinib | 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 | Abdominal pain | 27 Participants |
| Placebo and Erlotinib | 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 | Anemia | 51 Participants |
| Placebo and Erlotinib | 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 | Stomatitis | 27 Participants |
| Placebo and Erlotinib | 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 | Weight decreased | 58 Participants |
| Placebo and Erlotinib | 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 | Noncardiac chest pain | 24 Participants |
| Placebo and Erlotinib | 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 | Constipation | 54 Participants |
| Placebo and Erlotinib | 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 | Pain in extremity | 19 Participants |
| Placebo and Erlotinib | 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 | Pyrexia | 41 Participants |
| Placebo and Erlotinib | 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 | Pneumonia | 22 Participants |
| Placebo and Erlotinib | 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 | Back pain | 47 Participants |
| Placebo and Erlotinib | 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 | Hemoptysis | 19 Participants |
| Placebo and Erlotinib | 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 | Dry skin | 56 Participants |