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KATE2: A Study to Evaluate the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Participants With Human Epidermal Growth Factor-2 (HER2) Positive Locally Advanced or Metastatic Breast Cancer (BC) Who Received Prior Trastuzumab and Taxane Based Therapy

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT02924883
Collaborator
(none)
202
Enrollment
68
Locations
2
Arms
40.3
Actual Duration (Months)
3
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This Phase II, double-blind, randomized, placebo-controlled multicenter study will investigate the efficacy and safety of trastuzumab emtansine in combination with atezolizumab or atezolizumab-placebo in participants with HER2-positive locally advanced or metastatic BC who have received prior trastuzumab and taxane based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
202 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase II Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Atezolizumab-Placebo in Patients With HER2-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab and Taxane Based Therapy
Actual Study Start Date :
Sep 26, 2016
Actual Primary Completion Date :
Dec 11, 2017
Actual Study Completion Date :
Feb 6, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Trastuzumab Emtansine + Atezolizumab

Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion or matching Placebo followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (approximately 29 months)

Drug: Atezolizumab
Atezolizumab 1200 mg IV infusion
Other Names:
  • Tecentriq, RO5541267, MPDL3280A

    • Drug: Trastuzumab emtansine
    Trastuzumab emtansine 3.6 mg/kg IV infusion
    Other Names:
  • Kadcyla®, T-DM1, RO5304020

    • Other: Placebo
    Placebo matched to atezolizumab
    Active Comparator: Trastuzumab Emtansine + Placebo

    Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (approximately 29 months)

    Drug: Trastuzumab emtansine
    Trastuzumab emtansine 3.6 mg/kg IV infusion
    Other Names:
  • Kadcyla®, T-DM1, RO5304020

    • Other: Placebo
    Placebo matched to atezolizumab

    Outcome Measures

    Primary Outcome Measures

    1. Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) [Baseline up to approximately 15 months]

      PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.

    2. Percentage of Participants With Adverse Events [Baseline up to study completion, approximately 40 months]

      An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.

    Secondary Outcome Measures

    1. Overall Survival (OS) [Baseline up to study completion or death, whichever occurs first, approximately 40 months]

      OS was defined as the time from randomization to death from any cause.

    2. Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1 [Baseline up to approximately 15 months]

      An OR was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.

    3. Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1 [Baseline up to approximately 15 months]

      Duration of OR was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.

    4. Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine [Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)]

      Average post infusion Trastuzumab Emtansine concentration

    5. Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1) [Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)]

      Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion

    6. Cmax of Total Trastuzumab [Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)]

    7. Cmax of Atezolizumab [Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)]

      Average post infusion atezolizumab concentration

    8. Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab [Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)]

      ATAs are antibodies that inactivate the therapeutic effects of Atezolizumab. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).

    9. Percentage of Participants With ATAs to Trastuzumab Emtansine [Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)]

      ATAs are antibodies that inactivate the therapeutic effects of Trastuzumab Emtansine. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Archival tumor samples must be obtained from primary and/or metastatic sites

    • Able to submit tumor tissue that is evaluable for programmed death- ligand 1 (PD-L1) expression

    • HER-2 positive BC as defined by an immunohistochemistry score of 3 or gene amplified by in-situ hybridization as defined by a ratio of greater than or equal to (>=) 2.0 for the number of HER2 gene copies to the number of chromosome 17 copies

    • Histologically or cytologically confirmed invasive BC: incurable, unresectable, locally advanced BC previously treated with multimodality therapy or metastatic BC

    • Prior treatment for BC in the: adjuvant; unresectable locally advanced; or metastatic settings; which must include both, a taxane and trastuzumab (alone or in combination with another agent)

    • Progression must have occurred during or after most recent treatment for locally advanced/metastatic BC or within 6 months after completing adjuvant therapy

    • Participants must have measurable disease that is evaluable as per RECIST v1.1

    • Eastern Cooperative Oncology Group Performance Status of 0 or 1

    • Negative serum pregnancy test within 7 days of enrollment for pre-menopausal women and for women less than 12 months after the onset of menopause

    • Use of highly effective method of contraception as defined by the protocol

    Exclusion Criteria:

    • Prior treatment with trastuzumab emtansine, cluster of differentiation 137 agonists, anti-programmed death-1, or anti-PD-L1 therapeutic antibody or pathway-targeting agents

    • Receipt of any anti-cancer drug/biologic or investigational treatment within 21 days prior to Cycle 1 Day 1 except hormone therapy, which can be given up to 7 days prior to Cycle 1 Day 1; recovery of treatment related toxicity consistent with other eligibility criteria

    • Radiation therapy within 2 weeks prior to Cycle 1, Day 1

    • History of exposure to the cumulative doses of anthracyclines

    • History of other malignancy within the previous 5 years, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, Stage I uterine cancer, or participants who have undergone potentially curative therapy with no evidence of disease and are deemed by the treating physician to be at low risk for recurrence

    • Cardiopulmonary dysfunction, symptomatic pleural effusion, pericardial effusion, or ascites

    • Participants with severe infection within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia

    • Current severe, uncontrolled systemic disease

    • Major surgical procedure or significant traumatic injury within 28 days prior to randomization or anticipation of the need for major surgery during the course of study treatment

    • Clinically significant history of liver disease, including cirrhosis, current alcohol abuse, autoimmune hepatic disorders, sclerosis cholangitis or active infection with human immunodeficiency virus, hepatitis B virus, or hepatitis C virus

    • Need for current chronic corticosteroid therapy (>=10 mg of prednisone per day or an equivalent dose of other anti-inflammatory corticosteroids)

    • Spinal cord compression not definitively treated with surgery and/or radiation, or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for greater than (>) 2 weeks prior to randomization

    • Participants with known central nervous system disease

    • Leptomeningeal disease

    • History of autoimmune disease

    • Prior allogeneic stem cell or solid organ transplantation

    • Active tuberculosis

    • Receipt of a live, attenuated vaccine within 4 weeks prior to randomization or anticipation that such a live, attenuated vaccine will be required during the study

    • Treatment with systemic immunostimulatory agents within 4 weeks or five half-lives of the drug (whichever is shorter) prior to randomization

    • Treatment with systemic corticosteroids or other systemic immunosuppressive medications within 2 weeks prior to randomization, or anticipated requirement for systemic immunosuppressive medications during the trial

    • Participants who are breastfeeding, or intending to become pregnant during the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Breastlink Med Group Inc Orange California United States 92868
    2 University of Colorado Aurora Colorado United States 80045
    3 MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center) Washington District of Columbia United States 20007
    4 SCRI Florida Cancer Specialists South Fort Myers Florida United States 33916
    5 Florida Cancer Specialists; Saint Petersburg Saint Petersburg Florida United States 33719
    6 Northside Hospital Atlanta Georgia United States 30342
    7 Johns Hopkins Univ Med Center Baltimore Maryland United States 21231
    8 San Juan Oncology Associates Farmington New Mexico United States 87401
    9 Laura and ISAAC Perlmutter Cancer Center at NYU Langone. New York New York United States 10016
    10 Ohio State Uni Medical Center Columbus Ohio United States 43210
    11 Magee Womens Hospital Pittsburgh Pennsylvania United States 15213
    12 Cancer Care Associates of York York Pennsylvania United States 17403
    13 SCRI Tennessee Oncology Chattanooga Chattanooga Tennessee United States 37404
    14 Tennessee Oncology; Sarah Cannon Research Institute Nashville Tennessee United States 37203
    15 University of Washington Seattle Washington United States 98195
    16 St George Hospital; Cancer Care Centre Kogarah New South Wales Australia 2217
    17 Calvary Mater Newcastle Waratah New South Wales Australia 2298
    18 Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology Woolloongabba Queensland Australia 4102
    19 Peter MacCallum Cancer Center East Melbourne Victoria Australia 3002
    20 Peninsula and South Eastern Haematology and Oncology Group Frankston Victoria Australia 3199
    21 Sunshine Hospital St Albans Victoria Australia 3021
    22 St John of God Hospital; Bendat Cancer Centre Subiaco Western Australia Australia 6008
    23 Lakeridge Health Oshawa; Oncology Oshawa Ontario Canada L1G 2B9
    24 The Ottawa Hospital Cancer Centre; Oncology Ottawa Ontario Canada K1H 8L6
    25 Sunnybrook Odette Cancer Centre Toronto Ontario Canada M4N 3M5
    26 McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology Montreal Quebec Canada H3T 1E2
    27 McGill University; Glen Site; Oncology Montreal Quebec Canada H4A 3J1
    28 Hopital du Saint Sacrement Quebec City Quebec Canada G1S 4L8
    29 HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe Berlin Germany 13125
    30 Studienzentrum Berlin City Berlin Germany 14169
    31 Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum Essen Germany 45136
    32 Praxis für Interdisziplinäre Onkologie und Hämatologie GbR Freiburg Germany 79110
    33 Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg Heidelberg Germany 69120
    34 Institut für Versorgungsforschung in der Onkologie GbR Koblenz Koblenz Germany 56068
    35 IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A Napoli Campania Italy 80131
    36 A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2 Bologna Emilia-Romagna Italy 40138
    37 Ospedale Regionale Di Parma; Divisione Di Oncologia Medica Parma Emilia-Romagna Italy 43100
    38 Centro Di Riferimento Oncologico; SOC Oncologia Medica C Aviano Friuli-Venezia Giulia Italy 33081
    39 Centro Catanese Di Oncologia; Oncologia Medica Catania Sicilia Italy 95126
    40 Ospedale Santo Stefano, Azienda USL Centro Prato Prato Toscana Italy 59100
    41 National Cancer Center Goyang-si Korea, Republic of 10408
    42 Samsung Medical Center Seoul Korea, Republic of (0)6351
    43 Seoul National University Hospital Seoul Korea, Republic of 03080
    44 Severance Hospital, Yonsei University Health System Seoul Korea, Republic of 03722
    45 Asan Medical Center Seoul Korea, Republic of 05505
    46 Hospital Universitario Reina Sofia; Servicio de Oncologia Córdoba Cordoba Spain 14004
    47 Hospital Univ Vall d'Hebron; Servicio de Oncologia Barcelona Spain 08035
    48 Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología La Coruña Spain 15006
    49 Hospital Ramon y Cajal; Servicio de Oncologia Madrid Spain 28034
    50 Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia Valencia Spain 46010
    51 Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia Valencia Spain 46015
    52 Changhua Christian Hospital; Dept of Surgery Changhua Taiwan 500
    53 Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery Kaohsiung Taiwan 807
    54 China Medical University Hospital; Surgery Taichung Taiwan 404
    55 Chi-Mei Medical Center Tainan Taiwan 736
    56 Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology Taipei City Taiwan 11259
    57 VETERANS GENERAL HOSPITAL; Department of General Surgery Taipei Taiwan 00112
    58 National Taiwan Uni Hospital; General Surgery Taipei Taiwan 100
    59 Chang Gung Memorial Hospital - Linkou Taoyuan Taiwan 333
    60 Royal United Hospital; Oncology Department Bath United Kingdom BA1 3NG
    61 Beatson West of Scotland Cancer Centre Glasgow United Kingdom G12 0YN
    62 Royal Free Hospital; Dept of Oncology London United Kingdom NW3 2QG
    63 Royal Marsden Hosp NHS Fnd; Breast Unit London United Kingdom SW3 6JJ
    64 Christie Hospital; Breast Cancer Research Office Manchester United Kingdom M20 4QL
    65 Nottingham City Hospital Nottingham United Kingdom NG5 1PB
    66 Weston Park Hospital; Cancer Clinical Trials Centre Sheffield United Kingdom S10 2SJ
    67 Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit Sutton United Kingdom SM2 5PT
    68 Singleton Hospital; Pharmacy Swansea United Kingdom SA2 8QA

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02924883
    Other Study ID Numbers:
    • WO30085
    • 2015-004189-27
    First Posted:
    Oct 5, 2016
    Last Update Posted:
    Feb 17, 2021
    Last Verified:
    Jan 1, 2021
    Additional relevant MeSH terms:
    Breast Neoplasms
    Trastuzumab
    Ado-Trastuzumab Emtansine
    Atezolizumab
    Maytansine

    Study Results

    Participant Flow

    Recruitment Details
    Pre-assignment Detail
    Arm/Group Title Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months) Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
    Period Title: Overall Study
    STARTED 133 69
    COMPLETED 0 0
    NOT COMPLETED 133 69

    Baseline Characteristics

    Arm/Group Title Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo Total
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months) Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Total of all reporting groups
    Overall Participants 133 69 202
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    53.7
    (9.9)
    54.4
    (10.9)
    53.9
    (10.3)
    Sex: Female, Male (Count of Participants)
    Female
    131
    98.5%
    69
    100%
    200
    99%
    Male
    2
    1.5%
    0
    0%
    2
    1%
    Ethnicity (NIH/OMB) (Count of Participants)
    Hispanic or Latino
    10
    7.5%
    1
    1.4%
    11
    5.4%
    Not Hispanic or Latino
    114
    85.7%
    66
    95.7%
    180
    89.1%
    Unknown or Not Reported
    9
    6.8%
    2
    2.9%
    11
    5.4%
    Race (NIH/OMB) (Count of Participants)
    American Indian or Alaska Native
    0
    0%
    0
    0%
    0
    0%
    Asian
    49
    36.8%
    23
    33.3%
    72
    35.6%
    Native Hawaiian or Other Pacific Islander
    1
    0.8%
    0
    0%
    1
    0.5%
    Black or African American
    5
    3.8%
    1
    1.4%
    6
    3%
    White
    72
    54.1%
    44
    63.8%
    116
    57.4%
    More than one race
    1
    0.8%
    0
    0%
    1
    0.5%
    Unknown or Not Reported
    5
    3.8%
    1
    1.4%
    6
    3%
    Region (Number of Participants) [Number]
    USA
    21
    15.8%
    11
    15.9%
    32
    15.8%
    Western Europe
    50
    37.6%
    26
    37.7%
    76
    37.6%
    Rest of the World
    62
    46.6%
    32
    46.4%
    94
    46.5%
    Programmed Cell-Death Ligand 1 Immunohistochemistry status (Number of Participants) [Number]
    PD-L1 positive
    57
    42.9%
    27
    39.1%
    84
    41.6%
    PD-L1 negative
    76
    57.1%
    42
    60.9%
    118
    58.4%

    Outcome Measures

    1. Primary Outcome
    Title Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1)
    Description PFS was defined as the time from randomization to the first occurrence of disease progression or death from any cause, whichever occurred first, on the basis of investigator assessments. Progression was defined as at least a 20% increase in the sum of diameters of target lesions with an absolute increase of at least 5 millimeter (mm) or the appearance of one or more new lesions.
    Time Frame Baseline up to approximately 15 months

    Outcome Measure Data

    Analysis Population Description
    The intent-to-treat (ITT) population included all randomized participants grouped according to the treatment assigned at randomization.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 69 133
    Median (95% Confidence Interval) [months]
    6.8
    8.2
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine + Placebo, Trastuzumab Emtansine + Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.3332
    Comments
    Method Log Rank
    Comments The 2-sided log-rank test, was stratified by world region (Western Europe vs U.S. vs Rest of World) and PD-L1 status (IC 0 vs IC 1/2/3).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.82
    Confidence Interval () 95%
    0.55 to 1.23
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Percentage of Participants With Adverse Events
    Description An adverse event is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding, for example), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product. Preexisting conditions which worsen during a study are also considered as adverse events.
    Time Frame Baseline up to study completion, approximately 40 months

    Outcome Measure Data

    Analysis Population Description
    The safety analysis population consisted of all participants who received at least one dose of study drug. Safety analyses were based on the treatment that participants actually received.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 68 132
    Number [percentage of participants]
    97.0
    72.9%
    99.2
    143.8%
    3. Secondary Outcome
    Title Overall Survival (OS)
    Description OS was defined as the time from randomization to death from any cause.
    Time Frame Baseline up to study completion or death, whichever occurs first, approximately 40 months

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants grouped according to the treatment assigned at randomization.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 69 133
    Median (95% Confidence Interval) [Months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine + Placebo, Trastuzumab Emtansine + Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.2934
    Comments
    Method Log Rank
    Comments The 2-sided log-rank test was stratified by world region (Western Europe vs U.S. vs Rest of World) and PD-L1 status (IC 0 vs IC 1/2/3).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.74
    Confidence Interval () 95%
    0.42 to 1.30
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
    Description An OR was defined as a complete or partial response determined on 2 consecutive occasions ≥ 4 weeks apart using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete response was defined as the disappearance of all target and non-target lesions. Any pathological lymph nodes (whether target or non-target) must be < 10 mm on the short axis. Partial response was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum. Participants who had no post-baseline tumor assessment were counted as non-responders.
    Time Frame Baseline up to approximately 15 months

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants grouped according to the treatment assigned at randomization. In Participants with baseline measurable disease were considered for OR. In the atezolizumab arm, one patient was not ORR evaluable.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 69 132
    Number [Percentage of participants]
    43.5
    32.7%
    45.5
    65.9%
    5. Secondary Outcome
    Title Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
    Description Duration of OR was defined as the time from the first tumor assessment that was judged to indicate that the patient had an objective response to the time of first documented disease progression using RECIST v1.1 per investigator assessment or death from any cause, whichever occurred first.
    Time Frame Baseline up to approximately 15 months

    Outcome Measure Data

    Analysis Population Description
    The ITT population included all randomized participants grouped according to the treatment assigned at randomization. Participants with OR were considered for duration of OR.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 69 133
    Median (95% Confidence Interval) [Months]
    NA
    NA
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Trastuzumab Emtansine + Placebo, Trastuzumab Emtansine + Atezolizumab
    Comments
    Type of Statistical Test Superiority
    Comments
    Statistical Test of Hypothesis p-Value 0.6099
    Comments
    Method Log Rank
    Comments Stratified Cox proportional hazards model was stratified by world region (Western Europe, U.S., Rest of World) and PD-L1 status (IC 0, IC 1/2/3).
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.26
    Confidence Interval () 95%
    0.52 to 3.03
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
    Description Average post infusion Trastuzumab Emtansine concentration
    Time Frame Pre-infusion (0 hour [h]), 30 minutes (min) after end of infusion (EOI) (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days); at any time during study treatment/early discontinuation visit (approx. 40 months)

    Outcome Measure Data

    Analysis Population Description
    PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
    Arm/Group Title Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months) Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
    Measure Participants 110 50
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    63.9
    (116.9)
    73.2
    (47.5)
    7. Secondary Outcome
    Title Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
    Description Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion
    Time Frame Pre-infusion (0 h) on Day 1 Cycle 1 and 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4 (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 24 37
    Geometric Mean (Geometric Coefficient of Variation) [ng/mL]
    3.19
    (84.7)
    4.21
    (89.5)
    8. Secondary Outcome
    Title Cmax of Total Trastuzumab
    Description
    Time Frame Pre-infusion (0 h), 30 min after EOI (over 90 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycle 2 (each cycle = 21 days)

    Outcome Measure Data

    Analysis Population Description
    PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 50 110
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    86.5
    (26.4)
    79.5
    (58.3)
    9. Secondary Outcome
    Title Cmax of Atezolizumab
    Description Average post infusion atezolizumab concentration
    Time Frame Pre-infusion (0 h), 30 min after EOI (over 60 min) on Day 1 Cycles 1 and 4; pre-infusion (0 h) on Day 1 Cycles 2, 3, 8, and every 8 cycles thereafter (each cycle=21 days) up to 120 days after treatment completion/early discontinuation (approx. 40 months)

    Outcome Measure Data

    Analysis Population Description
    PK population included all participants who received at least one dose of trastuzumab emtansine with at least one post-dose concentration data point.
    Arm/Group Title Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 98
    Geometric Mean (Geometric Coefficient of Variation) [ug/mL]
    626
    (23.0)
    10. Secondary Outcome
    Title Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab
    Description ATAs are antibodies that inactivate the therapeutic effects of Atezolizumab. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).
    Time Frame Pre-infusion (0 h) on Day 1 Cycles 1, 2, 3, 4, 8, and every 8 cycles thereafter (each cycle = 21 days) up to 120 days after treatment completion or early discontinuation (approximately 40 months)

    Outcome Measure Data

    Analysis Population Description
    The analysis population included a patient with an ATA assay result from at least one post-baseline sample.
    Arm/Group Title Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 131
    Number [Percentage of participants]
    18.3
    13.8%
    11. Secondary Outcome
    Title Percentage of Participants With ATAs to Trastuzumab Emtansine
    Description ATAs are antibodies that inactivate the therapeutic effects of Trastuzumab Emtansine. Patients are considered to be ATA positive if they are ATA negative at baseline but develop an ATA response following study drug administration (treatment-induced ATA response), or if they are ATA positive at baseline and the titer of one or more post-baseline samples is at least 4-fold greater (i.e., ≥ 0.60 titer units) than the titer of the baseline sample (treatment-enhanced ATA response).
    Time Frame Pre-infusion (0 h) on Day 1 Cycles 1 and 4 (each cycle = 21 days); and at any time during study treatment/early discontinuation visit (approximately 40 months)

    Outcome Measure Data

    Analysis Population Description
    The analysis population included a patient with an ATA assay result from at least one post-baseline sample
    Arm/Group Title Trastuzumab Emtansine + Placebo Trastuzumab Emtansine + Atezolizumab
    Arm/Group Description Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months) Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months)
    Measure Participants 60 129
    Number [Percentage of Participants]
    0
    0%
    2.3
    3.3%

    Adverse Events

    Time Frame Baseline up to study completion, approximately 40 months
    Adverse Event Reporting Description The safety population is defined as all participants who received at least one dose of the study medication.
    Arm/Group Title Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Arm/Group Description Atezolizumab 1200 milligrams (mg) intravenous (IV) infusion followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor (up to study duration of approximately 40 months) Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor (up to study duration of approximately 40 months)
    All Cause Mortality
    Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 42/133 (31.6%) 22/67 (32.8%)
    Serious Adverse Events
    Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 52/133 (39.1%) 16/67 (23.9%)
    Blood and lymphatic system disorders
    Thrombocytopenia 2/133 (1.5%) 2 0/67 (0%) 0
    Anaemia 1/133 (0.8%) 1 0/67 (0%) 0
    Disseminated intravascular coagulation 0/133 (0%) 0 1/67 (1.5%) 1
    Cardiac disorders
    Atrial thrombosis 1/133 (0.8%) 1 0/67 (0%) 0
    Cardiac failure 0/133 (0%) 0 1/67 (1.5%) 1
    Ear and labyrinth disorders
    Vertigo 0/133 (0%) 0 1/67 (1.5%) 1
    Gastrointestinal disorders
    Vomiting 3/133 (2.3%) 3 0/67 (0%) 0
    Nausea 1/133 (0.8%) 1 1/67 (1.5%) 1
    Colitis 1/133 (0.8%) 1 0/67 (0%) 0
    Constipation 1/133 (0.8%) 1 0/67 (0%) 0
    Enteritis 0/133 (0%) 0 1/67 (1.5%) 1
    Abdominal pain 0/133 (0%) 0 2/67 (3%) 2
    Intra-abdominal haemorrhage 1/133 (0.8%) 1 0/67 (0%) 0
    General disorders
    Asthenia 0/133 (0%) 0 1/67 (1.5%) 1
    Fatigue 1/133 (0.8%) 1 0/67 (0%) 0
    Influenza like illness 2/133 (1.5%) 2 1/67 (1.5%) 1
    Malaise 1/133 (0.8%) 1 0/67 (0%) 0
    Non-cardiac chest pain 1/133 (0.8%) 1 0/67 (0%) 0
    Pyrexia 10/133 (7.5%) 12 0/67 (0%) 0
    Immune system disorders
    Haemophagocytic lymphohistiocytosis 1/133 (0.8%) 1 0/67 (0%) 0
    Infections and infestations
    Pneumonia 4/133 (3%) 4 1/67 (1.5%) 1
    Appendicitis 0/133 (0%) 0 1/67 (1.5%) 1
    Influenza 2/133 (1.5%) 2 0/67 (0%) 0
    Abscess jaw 1/133 (0.8%) 1 0/67 (0%) 0
    Breast cellulitis 1/133 (0.8%) 1 0/67 (0%) 0
    Catheter site infection 1/133 (0.8%) 1 0/67 (0%) 0
    Device related infection 1/133 (0.8%) 1 0/67 (0%) 0
    Infectious pleural effusion 1/133 (0.8%) 1 0/67 (0%) 0
    Lower respiratory tract infection 1/133 (0.8%) 1 0/67 (0%) 0
    Respiratory tract infection 1/133 (0.8%) 1 0/67 (0%) 0
    Sepsis 1/133 (0.8%) 1 2/67 (3%) 2
    Soft tissue infection 1/133 (0.8%) 1 0/67 (0%) 0
    Urinary tract infection 3/133 (2.3%) 3 2/67 (3%) 5
    Injury, poisoning and procedural complications
    Hip fracture 0/133 (0%) 0 1/67 (1.5%) 1
    Lower limb fracture 1/133 (0.8%) 1 0/67 (0%) 0
    Subdural haemorrhage 1/133 (0.8%) 1 0/67 (0%) 0
    Investigations
    Alanine aminotransferase increased 3/133 (2.3%) 3 0/67 (0%) 0
    Aspartate aminotransferase increased 3/133 (2.3%) 3 0/67 (0%) 0
    Metabolism and nutrition disorders
    Dehydration 0/133 (0%) 0 1/67 (1.5%) 1
    Decreased appetite 1/133 (0.8%) 1 0/67 (0%) 0
    Musculoskeletal and connective tissue disorders
    Osteonecrosis of jaw 1/133 (0.8%) 1 0/67 (0%) 0
    Pain in extremity 0/133 (0%) 0 1/67 (1.5%) 1
    Pathological fracture 0/133 (0%) 0 1/67 (1.5%) 1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Cancer pain 1/133 (0.8%) 1 0/67 (0%) 0
    Hepatic adenoma 1/133 (0.8%) 1 0/67 (0%) 0
    Uterine leiomyoma 1/133 (0.8%) 1 0/67 (0%) 0
    Nervous system disorders
    Seizure 1/133 (0.8%) 1 1/67 (1.5%) 1
    Brain oedema 2/133 (1.5%) 2 0/67 (0%) 0
    Cerebral haemorrhage 1/133 (0.8%) 1 0/67 (0%) 0
    Encephalopathy 1/133 (0.8%) 1 1/67 (1.5%) 1
    Neuropathy peripheral 0/133 (0%) 0 1/67 (1.5%) 1
    Psychiatric disorders
    Confusional state 1/133 (0.8%) 1 0/67 (0%) 0
    Panic attack 0/133 (0%) 0 1/67 (1.5%) 1
    Renal and urinary disorders
    IgA nephropathy 1/133 (0.8%) 1 0/67 (0%) 0
    Respiratory, thoracic and mediastinal disorders
    Pneumonitis 2/133 (1.5%) 2 1/67 (1.5%) 1
    Asthma 1/133 (0.8%) 1 0/67 (0%) 0
    Pneumothorax 1/133 (0.8%) 1 0/67 (0%) 0
    Epistaxis 1/133 (0.8%) 1 0/67 (0%) 0
    Interstitial lung disease 1/133 (0.8%) 1 0/67 (0%) 0
    Pleural effusion 1/133 (0.8%) 1 1/67 (1.5%) 1
    Other (Not Including Serious) Adverse Events
    Trastuzumab Emtansine + Atezolizumab Trastuzumab Emtansine + Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 130/133 (97.7%) 62/67 (92.5%)
    Blood and lymphatic system disorders
    Anaemia 24/133 (18%) 30 6/67 (9%) 7
    Neutropenia 13/133 (9.8%) 21 4/67 (6%) 4
    Thrombocytopenia 42/133 (31.6%) 105 12/67 (17.9%) 22
    Endocrine disorders
    Hypothyroidism 18/133 (13.5%) 19 3/67 (4.5%) 3
    Eye disorders
    Dry eye 11/133 (8.3%) 12 4/67 (6%) 4
    Lacrimation increased 7/133 (5.3%) 9 1/67 (1.5%) 1
    Vision blurred 7/133 (5.3%) 8 1/67 (1.5%) 1
    Gastrointestinal disorders
    Constipation 29/133 (21.8%) 38 10/67 (14.9%) 15
    Diarrhoea 34/133 (25.6%) 50 15/67 (22.4%) 18
    Dyspepsia 14/133 (10.5%) 21 3/67 (4.5%) 3
    Nausea 51/133 (38.3%) 84 29/67 (43.3%) 37
    Stomatitis 13/133 (9.8%) 21 2/67 (3%) 2
    Vomiting 27/133 (20.3%) 36 15/67 (22.4%) 19
    Abdominal pain 17/133 (12.8%) 20 3/67 (4.5%) 3
    Abdominal pain upper 10/133 (7.5%) 10 3/67 (4.5%) 8
    Dry mouth 22/133 (16.5%) 23 9/67 (13.4%) 10
    General disorders
    Asthenia 23/133 (17.3%) 35 5/67 (7.5%) 6
    Chills 19/133 (14.3%) 27 6/67 (9%) 8
    Fatigue 53/133 (39.8%) 87 30/67 (44.8%) 43
    Influenza like illness 12/133 (9%) 16 8/67 (11.9%) 8
    Mucosal inflammation 16/133 (12%) 21 1/67 (1.5%) 1
    Oedema peripheral 7/133 (5.3%) 9 4/67 (6%) 4
    Pyrexia 44/133 (33.1%) 72 12/67 (17.9%) 18
    Infections and infestations
    Nasopharyngitis 15/133 (11.3%) 20 6/67 (9%) 8
    Sinusitis 7/133 (5.3%) 9 2/67 (3%) 2
    Upper respiratory tract infection 18/133 (13.5%) 28 9/67 (13.4%) 12
    Urinary tract infection 9/133 (6.8%) 10 8/67 (11.9%) 10
    Injury, poisoning and procedural complications
    Fall 10/133 (7.5%) 14 3/67 (4.5%) 9
    Investigations
    Alanine aminotransferase increased 31/133 (23.3%) 44 13/67 (19.4%) 18
    Aspartate aminotransferase increased 40/133 (30.1%) 56 14/67 (20.9%) 19
    Blood alkaline phosphatase increased 11/133 (8.3%) 12 6/67 (9%) 8
    Gamma-glutamyltransferase increased 7/133 (5.3%) 7 2/67 (3%) 2
    Weight decreased 13/133 (9.8%) 13 3/67 (4.5%) 3
    Metabolism and nutrition disorders
    Decreased appetite 30/133 (22.6%) 52 12/67 (17.9%) 14
    Hypokalaemia 13/133 (9.8%) 16 4/67 (6%) 5
    Musculoskeletal and connective tissue disorders
    Arthralgia 26/133 (19.5%) 37 8/67 (11.9%) 9
    Myalgia 24/133 (18%) 26 10/67 (14.9%) 16
    Back pain 15/133 (11.3%) 19 8/67 (11.9%) 9
    Bone pain 8/133 (6%) 8 3/67 (4.5%) 8
    Muscle spasms 10/133 (7.5%) 13 7/67 (10.4%) 8
    Musculoskeletal pain 10/133 (7.5%) 12 6/67 (9%) 6
    Pain in extremity 9/133 (6.8%) 10 4/67 (6%) 5
    Nervous system disorders
    Dizziness 18/133 (13.5%) 18 9/67 (13.4%) 10
    Dysgeusia 6/133 (4.5%) 6 5/67 (7.5%) 6
    Headache 38/133 (28.6%) 62 17/67 (25.4%) 27
    Paraesthesia 9/133 (6.8%) 16 2/67 (3%) 2
    Neuropathy peripheral 18/133 (13.5%) 20 7/67 (10.4%) 8
    Peripheral sensory neuropathy 11/133 (8.3%) 11 5/67 (7.5%) 6
    Polyneuropathy 2/133 (1.5%) 2 4/67 (6%) 4
    Psychiatric disorders
    Anxiety 2/133 (1.5%) 2 6/67 (9%) 6
    Insomnia 14/133 (10.5%) 15 2/67 (3%) 2
    Respiratory, thoracic and mediastinal disorders
    Cough 25/133 (18.8%) 28 10/67 (14.9%) 12
    Dyspnoea 16/133 (12%) 19 5/67 (7.5%) 6
    Epistaxis 28/133 (21.1%) 39 10/67 (14.9%) 13
    Oropharyngeal pain 7/133 (5.3%) 8 1/67 (1.5%) 1
    Skin and subcutaneous tissue disorders
    Pruritus 23/133 (17.3%) 30 4/67 (6%) 5
    Rash 32/133 (24.1%) 42 6/67 (9%) 11
    Dry skin 11/133 (8.3%) 12 0/67 (0%) 0
    Vascular disorders
    Hypertension 4/133 (3%) 4 4/67 (6%) 4

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights

    Results Point of Contact

    Name/Title Medical Communications
    Organization Hoffmann-La Roche
    Phone 800 821-8590
    Email genentech@druginfo.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT02924883
    Other Study ID Numbers:
    • WO30085
    • 2015-004189-27
    First Posted:
    Oct 5, 2016
    Last Update Posted:
    Feb 17, 2021
    Last Verified:
    Jan 1, 2021