Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43857   clinical trials with a EudraCT protocol, of which   7284   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    TIGER-3: A Phase 3, Open-label, Multicenter, Randomized Study of Oral Rociletinib (CO-1686) Monotherapy Versus Single-agent Cytotoxic Chemotherapy in Patients with Mutant EGFR Non-small Cell Lung Cancer (NSCLC) After Failure of at Least 1 Previous EGFR-directed Tyrosine Kinase Inhibitor (TKI) and Platinum-doublet Chemotherapy

    Summary
    EudraCT number
    		 2014-003437-26
    Trial protocol
    		 GB   DE   NL   ES   IT  
    Global end of trial date
    29 Mar 2018

    Results information
    Results version number
    		 v2(current)
    This version publication date
    25 Sep 2019
    First version publication date
    02 Jun 2019
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Adding the following 2 secondary outcomes: Overall Survival (OS) and PK

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CO-1686-020
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02322281
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Clovis Oncology UK Ltd
    Sponsor organisation address
    Sheraton House, Castle Park, Cambridge, United Kingdom, CB3 0AX
    Public contact
    Dr Lindsey Rolfe, Clovis Oncology UK Ltd, +44 1223 370037, info@clovisoncology.com
    Scientific contact
    Dr Lindsey Rolfe, Clovis Oncology UK Ltd, +44 1223 370037, info@clovisoncology.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    29 Mar 2018
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    29 Mar 2018
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Mar 2018
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    To compare the anti-tumor efficacy of oral single-agent rociletinib, as measured by investigator assessment of the PFS, with that of single-agent cytotoxic chemotherapy in patients with EGFR-mutated, advanced/metastatic NSCLC after failure of at least 1 previous EGFR-directed TKI and at least 1 line of platinum-containing doublet chemotherapy
    Protection of trial subjects
    A data monitoring committee consisting of 3 of the clinical trial investigators and sponsor personnel met every 3 to 6 months to review and assess the safety and efficacy data, and provide recommendations regarding study continuation/discontinuation and protocol modifications.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    31 Dec 2014
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 12
    Country: Number of subjects enrolled
    Spain: 9
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    France: 8
    Country: Number of subjects enrolled
    Germany: 4
    Country: Number of subjects enrolled
    Italy: 15
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Korea, Republic of: 17
    Country: Number of subjects enrolled
    Taiwan: 25
    Country: Number of subjects enrolled
    United States: 49
    Worldwide total number of subjects
    149
    EEA total number of subjects
    55
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    88
    From 65 to 84 years
    58
    85 years and over
    3

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 149 subjects recruited from 83 sites in 10 countries and randomized (1:1) to treatment with rociletinib or single-agent cytotoxic chemotherapy (investigator's choice of pemetrexed, gemcitabine, docetaxel, or paclitaxel). Crossover to rociletinib treatment, permitted for comparator chemotherapy treated subjects but only after eligibility confirmed.

    Pre-assignment
    Screening details
    		 Eligible patients were ≥ 18 years of age with advanced/metastatic NSCLC that had evidence of a tumor with 1 or more activating EGFR mutations (excluding exon 20 insertion) and had undergone a biopsy or surgical resection of either primary or metastatic tumor tissue within 60 days of the first day of treatment.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Rociletinib 500 mg BID
    Arm description
    		 Starting dose of 500mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rociletinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Starting dose of 500mg. Taken orally twice daily (continuous 21 day treatment cycle).

    Arm title
    		 Rociletinib 625 mg BID
    Arm description
    		 Starting dose of 625mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Rociletinib
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Tablet
    Routes of administration
    Oral use
    Dosage and administration details
    Starting dose of 625mg. Taken orally twice daily (continuous 21 day treatment cycle).

    Arm title
    		 Chemotherapy
    Arm description
    		 Investigator's choice - Pemetrexed 500 mg/m2 given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 given intravenously on Day 1 and 8 of each 21-day cycle. Paclitaxel 80 mg/m2 given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Docetaxel 75 mg/m2 (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle, OR 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Treatment duration until radiographically confirmed disease progression.
    Arm type
    		 Active comparator

    Investigational medicinal product name
    Pemetrexed
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Pemetrexed administered at 500 mg/m2 intravenously (IV) on Day 1 of each 21-day cycle.

    Investigational medicinal product name
    Gemcitabine
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Gemcitabine administered at 1,250 mg/m2 IV on Days 1 and 8 of each 21-day cycle.

    Investigational medicinal product name
    Paclitaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Paclitaxel administered at 80 mg/m2 IV weekly as part of a continuous 21-day cycle (Days 1, 8, and 15 of each 21-day cycle).

    Investigational medicinal product name
    Docetaxel
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Docetaxel administered at 75 mg/m2 (60 mg/m2 in Asian patients) IV on Day 1 of each 21-day cycle, or 35 mg/m2 docetaxel IV weekly as part of a continuous 21-day cycle (Days 1, 8, and 15 of each 21-day cycle)

    Number of subjects in period 1
    		Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy
    Started
    53
    22
    74
    Crossed Over to Rociletinib 500 mg BID
    0
    0
    36
    Crossed Over to Rociletinib 625 mg BID
    0
    0
    3
    Completed
    0
    0
    0
    Not completed
    53
    22
    74
         Physician decision
    2
    -
    5
         Adverse Event
    3
    4
    6
         Death
    3
    3
    3
         Progressive Disease
    42
    14
    49
         Miscellaneous
    -
    -
    4
         Withdrawal by Subject
    1
    1
    6
         Study Terminated by Sponsor
    2
    -
    -
         Missing
    -
    -
    1

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Rociletinib 500 mg BID
    Reporting group description
    		 Starting dose of 500mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Rociletinib 625 mg BID
    Reporting group description
    		 Starting dose of 625mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Investigator's choice - Pemetrexed 500 mg/m2 given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 given intravenously on Day 1 and 8 of each 21-day cycle. Paclitaxel 80 mg/m2 given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Docetaxel 75 mg/m2 (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle, OR 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Treatment duration until radiographically confirmed disease progression.

    Reporting group values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy Total
    Number of subjects
    		 53 22 74 149
    Age categorical
    Units: Subjects
        18-64
    		 31 12 45 88
        65-84
    		 21 9 28 58
        >=85
    		 1 1 1 3
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 61.6 ( 11.66 ) 63.4 ( 12.30 ) 61.4 ( 9.84 ) -
    Gender categorical
    Units: Subjects
        Female
    		 35 13 39 87
        Male
    		 18 9 35 62
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 4 0 3 7
        Not Hispanic or Latino
    		 46 22 68 136
        Unknown or Not Reported
    		 3 0 3 6
    Race/Ethnicity, Customized 1
    Units: Subjects
        American Indian or Alaska Native
    		 0 0 0 0
        Asian
    		 23 6 30 59
        Black or African American
    		 2 0 3 5
        Native Hawaiian or Other Pacific Islander
    		 0 0 1 1
        White
    		 24 15 38 77
        Other
    		 0 1 1 2
        Missing
    		 4 0 1 5
    Race/Ethnicity, Customized 2
    Units: Subjects
        White
    		 24 15 38 77
        Asian
    		 23 6 30 59
        Non-White, Non-Asian
    		 6 1 6 13
    Number of Previous Therapies
    Units: number
        median (full range (min-max))
    		 3.0 (1.0 to 8.0) 3.0 (2.0 to 6.0) 3.0 (0.0 to 13.0) -
    Time Since Diagnosis of NSCLC [1]
    [1] Measure Analysis Population Description: Information missing for one patient in the Chemotherapy treatment group.
    Units: Months
        arithmetic mean (standard deviation)
    		 42.6 ( 35.54 ) 37.5 ( 16.92 ) 39.0 ( 25.10 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Rociletinib 500 mg BID
    Reporting group description
    		 Starting dose of 500mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Rociletinib 625 mg BID
    Reporting group description
    		 Starting dose of 625mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Investigator's choice - Pemetrexed 500 mg/m2 given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 given intravenously on Day 1 and 8 of each 21-day cycle. Paclitaxel 80 mg/m2 given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Docetaxel 75 mg/m2 (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle, OR 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Treatment duration until radiographically confirmed disease progression.

    Primary: Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS)

    		 Close Top of page
    End point title
    		 Progression Free Survival (PFS) According to RECIST Version 1.1 as Determined by Investigator Review (invPFS) [1]
    End point description
    Median InvPFS was calculated as 1+ the number of days from the date of randomization to documented radiographic progression as determined by the investigator, or death due to any cause, whichever occurs first. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered progression. 1 patient in the Chemotherapy treatment group was not included in the analysis, due to discontinuation of study shortly after randomization and prior to first dose of study drug.
    End point type
    Primary
    End point timeframe
    Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for PFS.
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per EMA feedback, the statistical analyses section can not accommodate the end point results for this study. Therefore, for each end point, all statistical analyses details are provided in the End point values sections.
    End point values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy
    Number of subjects analysed
    53 [2]
    22 [3]
    73 [4]
    Units: PFS Days
    125
    166
    77
    Notes
    [2] - PFS Days - Confidence interval: level 95%, 2-sided, lower limit 79, upper limit 165
    [3] - PFS Days - Confidence interval: level 95%, 2-sided, lower limit 56, upper limit 246
    [4] - PFS Days - Confidence interval: level 95%, 2-sided, lower limit 42, upper limit 88
    No statistical analyses for this end point

    Secondary: Percentage of Patients With Confirmed Response

    		 Close Top of page
    End point title
    		 Percentage of Patients With Confirmed Response
    End point description
    Percentage of patients with best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression or recurrence. Per RECIST v1.1 for target lesions: CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to < 10 mm. PR is at least 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response (OR) is the best response recorded from the start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The patient's best response assignment was dependent on the achievement of both measurement and confirmation criteria. 1 patient in the Chemotherapy group was not included in analysis due to discontinuation after randomization and prior to 1st dose.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to End of Treatment, up to approximately 35 months. This Time Frame includes the cross-over period, however, participants who crossed over to rociletinib were not analyzed for best overall confirmed response.
    End point values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy
    Number of subjects analysed
    53 [5]
    22 [6]
    73 [7]
    Units: Percentage of participants
    17
    18
    8
    Notes
    [5] - Percentage of Patients - Confidence interval: level 95%, 2-sided, lower limit 8.1, upper limit 29.8
    [6] - Percentage of Patients - Confidence interval: level 95%, 2-sided, lower limit 5.2, upper limit 40.3
    [7] - Percentage of Patients - Confidence interval: level 95%, 2-sided, lower limit 3.1, upper limit 17
    No statistical analyses for this end point

    Secondary: Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment

    		 Close Top of page
    End point title
    		 Duration of Response (DOR) According to RECIST Version 1.1 as Determined by Investigator Assessment
    End point description
    Median Duration of Response in patients with confirmed response (CR or PR) per investigator. The DOR was measured from date best response is first recorded until first date that progressive disease is objectively documented. For patients who continue treatment post-progression, first date of progression was used for the analysis. Per RECIST v1.1 for target lesions: CR is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. PR is at least a 30% decrease in sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter. Overall Response is the best response from start of the treatment until disease progression/recurrence (taking as reference for progressive disease the smallest measurements recorded since the treatment started). The overall number of patients in the Chemotherapy arm does not include those who crossed over into the Rociletinib treatment groups
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to End of Treatment, up to approximately 35 months
    End point values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy
    Number of subjects analysed
    9 [8]
    4 [9]
    6 [10]
    Units: Days
    335
    275
    206
    Notes
    [8] - DOR Days - Confidence interval: level 95%, 2-sided, lower limit 77, upper limit 418
    [9] - DOR Days - Confidence interval: level 95%, 2-sided, lower limit 167, upper limit 375
    [10] - DOR Days - Confidence interval: level 95%, 2-sided, lower limit 136, upper limit not available
    No statistical analyses for this end point

    Secondary: Overall Survival (OS)

    		 Close Top of page
    End point title
    		 Overall Survival (OS)
    End point description
    Median OS was calculated as 1+ the number of days from randomization to death due to any cause. Patients without a documented date of death were censored on the date the patient was last known to be alive. One patient in the Rociletinib 500 and 2 patients in the Chemotherapy treatment group were not included in the analysis because their OS data was not collected. One additional patient in the Chemotherapy group was not included due to discontinuation from study shortly after randomization and prior to first dose of study drug.
    End point type
    Secondary
    End point timeframe
    Cycle 1 Day 1 to date of death, assessed up to 3 years
    End point values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy
    Number of subjects analysed
    52 [11]
    22 [12]
    71 [13]
    Units: Median Days
    665
    541
    348
    Notes
    [11] - Confidence interval: level 95%, 2-sided, lower limit 232, upper limit not available
    [12] - Confidence interval: level 95%, 2-sided, lower limit 173, upper limit not available
    [13] - Confidence interval: level 95%, 2-sided, lower limit 231, upper limit 522
    No statistical analyses for this end point

    Secondary: Plasma PK for Patients Treated with Rociletinib Based on Sparse Sampling

    		 Close Top of page
    End point title
    		 Plasma PK for Patients Treated with Rociletinib Based on Sparse Sampling [14]
    End point description
    Blood samples were drawn for PK analysis at 21 ± 3 day intervals for the first 6 months (Day 1 of Cycles 2 to 7 inclusive). The sample could be taken predose or postdose. Plasma concentrations are presented for Rociletinib and 3 metabolites (M460, M502, M544). Population Description: A small subset of patients treated with rociletinib (ie, patients randomized to receive rociletinib or who crossed over to receive rociletinib following treatment with single agent cytotoxic chemotherapy). Note: 1 sample was analyzed in the 500mg treatment group and 33 samples were analyzed in the 625mg treatment group. 2 patients in the 625mg treatment group had M502 values at upper limit of quantification (ULOQ) which were set as missing values.
    End point type
    Secondary
    End point timeframe
    Cycles 2 Day 1 to Cycle 7 Day 1, or approximately 6 months
    Notes
    [14] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Per EMA feedback, the statistical analyses section can not accommodate the end point results for this study. Therefore, for each end point, all statistical analyses details are provided in the End point values sections
    End point values
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID
    Number of subjects analysed
    1 [15]
    10 [16]
    Units: Rociletinib plasma concentration (ng/mL)
    80
    207
    Notes
    [15] - Metabolite ng/mL: M460=20, M502=573, M544=765
    [16] - Metabolite ng/mL (range): M460=555 (144-1200), M502=3260 (98.4-4880), M544=525 (20-3640)
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from the date of first dose of study drug and until 28 days after last dose of study drug, an average of 6 months.
    Adverse event reporting additional description
    If subject experiences the same preferred term (system organ class) multiple times, the subject was counted only once for that preferred term. Treatment Arm/Groups for subjects who crossed over to Rociletinib from Chemotherapy are included. 1 subject in Chemo group was not included due to discontinuation after randomization and prior to first dose.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    18.0
    Reporting groups
    Reporting group title
    Rociletinib 500 mg BID
    Reporting group description
    		 Starting dose of 500mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Rociletinib 625 mg BID
    Reporting group description
    		 Starting dose of 625mg. Taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Chemotherapy
    Reporting group description
    		 Investigator's choice - Pemetrexed 500 mg/m2 given intravenously on Day 1 of each 21-day cycle. Gemcitabine 1250 mg/m2 given intravenously on Day 1 and 8 of each 21day cycle. Paclitaxel 80 mg/m2 given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Docetaxel 75 mg/m2 (60 mg/m2 for patients residing in East-Asian territories) given intravenously on Day 1 of each 21-day cycle, OR 35 mg/m2 docetaxel given intravenously on a weekly basis as part of a continuous 21-day cycle; i.e. dosing will be on Days 1, 8, and 15 of each 21-day cycle. Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Crossover from Chemotherapy to Rociletinib 500 mg BID
    Reporting group description
    		 Patients initially randomized to comparator chemotherapy had the option to cross over to rociletinib following disease progression per RECIST Version 1.1. Rociletinib starting dose of 500 mg taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression.

    Reporting group title
    Crossover From Chemotherapy to Rociletinib 625 mg BID
    Reporting group description
    		 Patients initially randomized to comparator chemotherapy had the option to cross over to rociletinib following disease progression per RECIST Version 1.1. Rociletinib starting dose of 625 mg taken orally twice daily (continuous 21 day treatment cycle). Treatment duration until radiographically confirmed disease progression

    Serious adverse events
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy Crossover from Chemotherapy to Rociletinib 500 mg BID Crossover From Chemotherapy to Rociletinib 625 mg BID
    Total subjects affected by serious adverse events
         subjects affected / exposed
    23 / 53 (43.40%)
    7 / 22 (31.82%)
    23 / 73 (31.51%)
    18 / 36 (50.00%)
    1 / 3 (33.33%)
         number of deaths (all causes)
    10
    3
    3
    6
    0
         number of deaths resulting from adverse events
    10
    3
    3
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    5 / 53 (9.43%)
    1 / 22 (4.55%)
    2 / 73 (2.74%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 5
    0 / 1
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 5
    0 / 1
    0 / 2
    0 / 2
    0 / 0
    Metastases to meninges
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    Metastatic pain
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Fatigue
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General physical health deterioration
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    General oedema
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypothermia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyrexia
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sudden death
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    Non-cardiac chest pain
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Prostatic obstruction
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    2 / 53 (3.77%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Haemoptysis
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoxia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pleural effusion
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    1 / 3 (33.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 2
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonitis
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumothorax
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary embolism
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Subdural haematoma
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Angina pectoris
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Atrial Fibrillation
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bradycardia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cardio-pulmonary arrest
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Myocardial infarction
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nodal arrhythmia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Ventricular fibrillation
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Nervous system disorders
    Complex partial seizures
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sciatica
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Febrile neutropenia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Neutropenia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anaemia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Eye disorders
    Cataract
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 3
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Diarrhoea
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Dysphagia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 3
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nausea
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    2 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Small intestinal obstruction
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Upper gastrointestinal haemorrhage
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vomiting
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Anal fistula
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pancreatitis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
    Pancreatitis acute
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bile duct stone
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Cholecystitis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Back pain
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Intervertabral disc protrusion
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Flank pain
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Mobility decreased
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pain in extremity
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Gastroenteritis
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infection
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
    Influenza
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lower respiratory tract infection
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    3 / 53 (5.66%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 3
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pyelonephritis
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Enterococcal bacteraemia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Peritonitis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypercalcaemia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hyperglycaemia
         subjects affected / exposed
    3 / 53 (5.66%)
    1 / 22 (4.55%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    4 / 4
    1 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypoalbuminaemia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Hypokalaemia
         subjects affected / exposed
    0 / 53 (0.00%)
    1 / 22 (4.55%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Rociletinib 500 mg BID Rociletinib 625 mg BID Chemotherapy Crossover from Chemotherapy to Rociletinib 500 mg BID Crossover From Chemotherapy to Rociletinib 625 mg BID
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    53 / 53 (100.00%)
    21 / 22 (95.45%)
    71 / 73 (97.26%)
    35 / 36 (97.22%)
    3 / 3 (100.00%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Malignant neoplasm progression
         subjects affected / exposed
    7 / 53 (13.21%)
    1 / 22 (4.55%)
    2 / 73 (2.74%)
    2 / 36 (5.56%)
    1 / 3 (33.33%)
         occurrences all number
    7
    1
    2
    2
    2
    Vascular disorders
    Hypertension
         subjects affected / exposed
    6 / 53 (11.32%)
    0 / 22 (0.00%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    10
    0
    2
    0
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    10 / 53 (18.87%)
    1 / 22 (4.55%)
    10 / 73 (13.70%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    16
    1
    10
    6
    0
    Chest discomfort
         subjects affected / exposed
    3 / 53 (5.66%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    0
    0
    0
    Chest pain
         subjects affected / exposed
    2 / 53 (3.77%)
    2 / 22 (9.09%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    7
    2
    4
    0
    0
    Fatigue
         subjects affected / exposed
    16 / 53 (30.19%)
    12 / 22 (54.55%)
    18 / 73 (24.66%)
    4 / 36 (11.11%)
    1 / 3 (33.33%)
         occurrences all number
    23
    21
    37
    6
    1
    Non-cardiac chest pain
         subjects affected / exposed
    3 / 53 (5.66%)
    0 / 22 (0.00%)
    5 / 73 (6.85%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    5
    4
    0
    Oedema peripheral
         subjects affected / exposed
    5 / 53 (9.43%)
    1 / 22 (4.55%)
    6 / 73 (8.22%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    6
    1
    9
    1
    0
    Pyrexia
         subjects affected / exposed
    5 / 53 (9.43%)
    2 / 22 (9.09%)
    7 / 73 (9.59%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    6
    2
    7
    0
    0
    General physical health deterioration
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    15 / 53 (28.30%)
    6 / 22 (27.27%)
    14 / 73 (19.18%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    19
    7
    17
    8
    0
    Dyspnoea
         subjects affected / exposed
    8 / 53 (15.09%)
    5 / 22 (22.73%)
    10 / 73 (13.70%)
    6 / 36 (16.67%)
    0 / 3 (0.00%)
         occurrences all number
    13
    7
    13
    8
    0
    Oropharyngeal pain
         subjects affected / exposed
    6 / 53 (11.32%)
    1 / 22 (4.55%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    7
    1
    4
    0
    0
    Pleural effusion
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    6
    0
    1
    Pneumonitis
         subjects affected / exposed
    4 / 53 (7.55%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    5
    0
    0
    1
    0
    Pulmonary embolism
         subjects affected / exposed
    0 / 53 (0.00%)
    2 / 22 (9.09%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    2
    0
    0
    0
    Epistaxis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Haemoptysis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Sputum increased
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    1 / 53 (1.89%)
    1 / 22 (4.55%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    4
    0
    0
    Insomnia
         subjects affected / exposed
    8 / 53 (15.09%)
    1 / 22 (4.55%)
    10 / 73 (13.70%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    10
    2
    13
    2
    0
    Investigations
    Alanine aminotransferase increased
         subjects affected / exposed
    4 / 53 (7.55%)
    2 / 22 (9.09%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    13
    2
    4
    0
    0
    Aspartate aminotransferase increased
         subjects affected / exposed
    5 / 53 (9.43%)
    1 / 22 (4.55%)
    5 / 73 (6.85%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    16
    1
    7
    1
    0
    Blood alkaline phosphatase increased
         subjects affected / exposed
    3 / 53 (5.66%)
    0 / 22 (0.00%)
    3 / 73 (4.11%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    6
    0
    3
    1
    0
    Blood bilirubin increased
         subjects affected / exposed
    4 / 53 (7.55%)
    4 / 22 (18.18%)
    1 / 73 (1.37%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    6
    4
    1
    5
    0
    Blood creatinine increased
         subjects affected / exposed
    4 / 53 (7.55%)
    1 / 22 (4.55%)
    3 / 73 (4.11%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    6
    2
    4
    2
    0
    Electrocardiogram QT prolonged
         subjects affected / exposed
    10 / 53 (18.87%)
    10 / 22 (45.45%)
    0 / 73 (0.00%)
    7 / 36 (19.44%)
    1 / 3 (33.33%)
         occurrences all number
    24
    24
    0
    16
    1
    Lymphocyte count decreased
         subjects affected / exposed
    2 / 53 (3.77%)
    1 / 22 (4.55%)
    4 / 73 (5.48%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    4
    2
    12
    1
    0
    Neutrophil count decreased
         subjects affected / exposed
    2 / 53 (3.77%)
    0 / 22 (0.00%)
    10 / 73 (13.70%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    2
    0
    22
    0
    0
    Platelet count decreased
         subjects affected / exposed
    3 / 53 (5.66%)
    1 / 22 (4.55%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    1
    7
    0
    0
    Weight decreased
         subjects affected / exposed
    10 / 53 (18.87%)
    4 / 22 (18.18%)
    4 / 73 (5.48%)
    1 / 36 (2.78%)
    1 / 3 (33.33%)
         occurrences all number
    10
    6
    4
    1
    1
    White blood cell count decreased
         subjects affected / exposed
    2 / 53 (3.77%)
    3 / 22 (13.64%)
    9 / 73 (12.33%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    4
    3
    22
    1
    0
    Nervous system disorders
    Dizziness
         subjects affected / exposed
    4 / 53 (7.55%)
    3 / 22 (13.64%)
    2 / 73 (2.74%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    4
    3
    2
    2
    0
    Headache
         subjects affected / exposed
    6 / 53 (11.32%)
    5 / 22 (22.73%)
    5 / 73 (6.85%)
    1 / 36 (2.78%)
    1 / 3 (33.33%)
         occurrences all number
    8
    6
    5
    1
    1
    Migraine
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Paraesthesia
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 53 (13.21%)
    2 / 22 (9.09%)
    18 / 73 (24.66%)
    5 / 36 (13.89%)
    1 / 3 (33.33%)
         occurrences all number
    9
    7
    28
    6
    1
    Leukopenia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    5 / 73 (6.85%)
    4 / 36 (11.11%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    10
    10
    0
    Neutropenia
         subjects affected / exposed
    0 / 53 (0.00%)
    2 / 22 (9.09%)
    9 / 73 (12.33%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    0
    3
    21
    7
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    5 / 73 (6.85%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    6
    3
    0
    Eye disorders
    Cataract
         subjects affected / exposed
    5 / 53 (9.43%)
    3 / 22 (13.64%)
    1 / 73 (1.37%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    7
    6
    1
    3
    0
    Vision blurred
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    1 / 3 (33.33%)
         occurrences all number
    0
    0
    0
    0
    1
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    6 / 53 (11.32%)
    0 / 22 (0.00%)
    3 / 73 (4.11%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    9
    0
    4
    0
    0
    Constipation
         subjects affected / exposed
    6 / 53 (11.32%)
    2 / 22 (9.09%)
    10 / 73 (13.70%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    7
    2
    10
    3
    0
    Diarrhoea
         subjects affected / exposed
    33 / 53 (62.26%)
    15 / 22 (68.18%)
    12 / 73 (16.44%)
    13 / 36 (36.11%)
    1 / 3 (33.33%)
         occurrences all number
    54
    23
    12
    22
    1
    Dry mouth
         subjects affected / exposed
    3 / 53 (5.66%)
    1 / 22 (4.55%)
    2 / 73 (2.74%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    4
    1
    2
    3
    0
    Dyspepsia
         subjects affected / exposed
    3 / 53 (5.66%)
    5 / 22 (22.73%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    6
    5
    1
    0
    0
    Gastroesophageal reflux disease
         subjects affected / exposed
    3 / 53 (5.66%)
    2 / 22 (9.09%)
    2 / 73 (2.74%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    4
    2
    2
    2
    0
    Nausea
         subjects affected / exposed
    19 / 53 (35.85%)
    9 / 22 (40.91%)
    20 / 73 (27.40%)
    7 / 36 (19.44%)
    1 / 3 (33.33%)
         occurrences all number
    27
    14
    29
    8
    1
    Vomiting
         subjects affected / exposed
    10 / 53 (18.87%)
    8 / 22 (36.36%)
    6 / 73 (8.22%)
    6 / 36 (16.67%)
    2 / 3 (66.67%)
         occurrences all number
    14
    11
    7
    10
    4
    Stomatitis
         subjects affected / exposed
    3 / 53 (5.66%)
    1 / 22 (4.55%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    1
    4
    0
    0
    Pancreatitis
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    3
    0
    Skin and subcutaneous tissue disorders
    Alopecia
         subjects affected / exposed
    3 / 53 (5.66%)
    0 / 22 (0.00%)
    8 / 73 (10.96%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    3
    0
    8
    0
    0
    Rash
         subjects affected / exposed
    5 / 53 (9.43%)
    0 / 22 (0.00%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    6
    0
    4
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    0
    2
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    4 / 73 (5.48%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    4
    3
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    5 / 53 (9.43%)
    0 / 22 (0.00%)
    6 / 73 (8.22%)
    3 / 36 (8.33%)
    0 / 3 (0.00%)
         occurrences all number
    5
    0
    10
    3
    0
    Back pain
         subjects affected / exposed
    6 / 53 (11.32%)
    3 / 22 (13.64%)
    10 / 73 (13.70%)
    1 / 36 (2.78%)
    2 / 3 (66.67%)
         occurrences all number
    7
    4
    14
    2
    2
    Bone pain
         subjects affected / exposed
    0 / 53 (0.00%)
    0 / 22 (0.00%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    0
    4
    0
    0
    Flank pain
         subjects affected / exposed
    0 / 53 (0.00%)
    2 / 22 (9.09%)
    1 / 73 (1.37%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    0
    5
    1
    0
    0
    Muscle spasms
         subjects affected / exposed
    8 / 53 (15.09%)
    3 / 22 (13.64%)
    0 / 73 (0.00%)
    3 / 36 (8.33%)
    1 / 3 (33.33%)
         occurrences all number
    9
    3
    0
    4
    1
    Muscular weakness
         subjects affected / exposed
    1 / 53 (1.89%)
    2 / 22 (9.09%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    1
    2
    3
    0
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    3 / 53 (5.66%)
    2 / 22 (9.09%)
    6 / 73 (8.22%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    3
    3
    9
    2
    0
    Musculoskeletal pain
         subjects affected / exposed
    6 / 53 (11.32%)
    2 / 22 (9.09%)
    3 / 73 (4.11%)
    4 / 36 (11.11%)
    0 / 3 (0.00%)
         occurrences all number
    4
    8
    2
    5
    0
    Myalgia
         subjects affected / exposed
    7 / 53 (13.21%)
    3 / 22 (13.64%)
    2 / 73 (2.74%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    8
    5
    3
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    4 / 73 (5.48%)
    4 / 36 (11.11%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    6
    5
    0
    Infections and infestations
    Nasopharyngitis
         subjects affected / exposed
    3 / 53 (5.66%)
    0 / 22 (0.00%)
    0 / 73 (0.00%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    0
    0
    0
    0
    Pneumonia
         subjects affected / exposed
    4 / 53 (7.55%)
    2 / 22 (9.09%)
    0 / 73 (0.00%)
    1 / 36 (2.78%)
    0 / 3 (0.00%)
         occurrences all number
    4
    2
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    4 / 53 (7.55%)
    2 / 22 (9.09%)
    3 / 73 (4.11%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    5
    2
    3
    0
    0
    Urinary tract infection
         subjects affected / exposed
    4 / 53 (7.55%)
    1 / 22 (4.55%)
    2 / 73 (2.74%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    8
    2
    3
    0
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    19 / 53 (35.85%)
    9 / 22 (40.91%)
    10 / 73 (13.70%)
    8 / 36 (22.22%)
    1 / 3 (33.33%)
         occurrences all number
    30
    12
    12
    11
    1
    Hyperglycaemia
         subjects affected / exposed
    30 / 53 (56.60%)
    14 / 22 (63.64%)
    6 / 73 (8.22%)
    12 / 36 (33.33%)
    2 / 3 (66.67%)
         occurrences all number
    84
    33
    8
    41
    4
    Hypokalaemia
         subjects affected / exposed
    7 / 53 (13.21%)
    6 / 22 (27.27%)
    3 / 73 (4.11%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    9
    9
    3
    0
    0
    Hypomagnesaemia
         subjects affected / exposed
    4 / 53 (7.55%)
    2 / 22 (9.09%)
    4 / 73 (5.48%)
    0 / 36 (0.00%)
    0 / 3 (0.00%)
         occurrences all number
    4
    2
    4
    0
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 53 (1.89%)
    3 / 22 (13.64%)
    2 / 73 (2.74%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    1
    3
    2
    2
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 53 (1.89%)
    0 / 22 (0.00%)
    1 / 73 (1.37%)
    2 / 36 (5.56%)
    0 / 3 (0.00%)
         occurrences all number
    1
    0
    1
    2
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    31 Oct 2014
    In global Amendment 1, the planned enrollment was increased to approximately 600 patients, which increased the number of targeted PFS events from 350 to 400 events to strengthen the statistical analyses. Other revisions included clarification/revision of inclusion and exclusion criteria and updates to safety management, such as requiring a follow-up scan to confirm that treated brain metastasis remain controlled without evidence of new lesions, and updated guidance on the management of hyperglycemia.
    27 Apr 2015
    Global Amendment 2 included decreasing the starting dose of rociletinib from 625 mg BID to 500 mg BID and specifying that a dose reduction for patients initially treated at 625 mg BID was allowed only if necessitated by unacceptable toxicity. Supportive analysis of Independent radiology review of PFS (irrPFS) and stratification subgroups to the statistical analyses were added. Additional information was provided on the management of prolonged QTC and hyperglycemia, and tumor assessments were revised to minimize scan parameters if not necessary, including exception for scans following discontinuation without progression, to allow for local variations in scan requirements. This global amendment also specified that creatinine clearance ≥ 45 ml/min be used instead of plasma creatinine in the inclusion criteria and single-agent cytotoxic medication sections. Fasting serum glucose within normal ranges was incorporated into the global protocol amendment as an inclusion criterion.
    07 Sep 2016
    Extension Phase and Early Termination of the Study -- Clovis announced on 05 May 2016 that enrollment would be terminated due to a decision to halt the clinical development of rociletinib. The purpose of Protocol Amendment 4 was to add a new Extension Phase to allow patients who continued to derive clinical benefit from study treatment to remain on-study, at the discretion of the Principal Investigator, but to avoid unnecessary collection of data that would no longer be analyzed or required for regulatory purposes whilst maintaining an appropriate level of safety monitoring. Patients were administered rociletinib daily at 500 mg BID (or 625 mg BID under Protocol Amendment 1). A new schedule of assessments for the Extension Phase, as well as a complete description of procedures, was provided, which replaced all prior assessment schedules. Treatment could continue until disease progression or intolerable toxicity; for patients who wished to continue rociletinib treatment post-progression or for patients who wished to cross over to rociletinib treatment following progression on chemotherapy, a full exploration of alternative treatment options between patients and their treating physicians took place prior to making that decision.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    12 May 2016
    Due to an internal corporate decision announced on 05 May 2016 to suspend the development of rociletinib, no new patients were permitted to enter screening for enrollment into any ongoing Clovis-sponsored rociletinib clinical study. Patients who were in screening as of that date could enroll on or before 12 May 2016 if they met eligibility requirements. At this time, there were 149 patients randomized.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    Due to early study termination, only 149 of 600 planned patients were randomized.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Wed Apr 24 10:15:12 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA