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Metastatic Breast CancerPhase 2KATE2NCT02924883

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

A Phase 2 study testing Atezolizumab and Trastuzumab emtansine in people with Metastatic Breast Cancer, run by Hoffmann-La Roche at 68 sites in 9 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Metastatic Breast Cancer
What is being tested?
Atezolizumab and Trastuzumab emtansine
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
202 participants
Where
68 sitesin 9 countries
Study dates
26 Sep 2016to 6 Feb 2020
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
Show all 10Show fewer
  • 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

Who cannot join

  • 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
Show all 21Show fewer
  • 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

Trial locations and contacts

68 sites in 9 countries.

68 sites in 9 countries

United States15 sites

  • Northside Hospital

    Atlanta, Georgia, 30342

  • University of Colorado

    Aurora, Colorado, 80045

  • Johns Hopkins Univ Med Center

    Baltimore, Maryland, 21231

  • SCRI Tennessee Oncology Chattanooga

    Chattanooga, Tennessee, 37404

  • Ohio State Uni Medical Center

    Columbus, Ohio, 43210

  • San Juan Oncology Associates

    Farmington, New Mexico, 87401

  • SCRI Florida Cancer Specialists South

    Fort Myers, Florida, 33916

  • Tennessee Oncology; Sarah Cannon Research Institute

    Nashville, Tennessee, 37203

  • Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

    New York, New York, 10016

  • Breastlink Med Group Inc

    Orange, California, 92868

  • Magee Womens Hospital

    Pittsburgh, Pennsylvania, 15213

  • University of Washington

    Seattle, Washington, 98195

  • Florida Cancer Specialists; Saint Petersburg

    St. Petersburg, Florida, 33719

  • MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

    Washington D.C., District of Columbia, 20007

  • Cancer Care Associates of York

    York, Pennsylvania, 17403

Other trials in United States

United Kingdom9 sites

  • Royal United Hospital; Oncology Department

    Bath, BA1 3NG

  • Beatson West of Scotland Cancer Centre

    Glasgow, G12 0YN

  • Royal Free Hospital; Dept of Oncology

    London, NW3 2QG

  • Royal Marsden Hosp NHS Fnd; Breast Unit

    London, SW3 6JJ

  • Christie Hospital; Breast Cancer Research Office

    Manchester, M20 4QL

  • Nottingham City Hospital

    Nottingham, NG5 1PB

  • Weston Park Hospital; Cancer Clinical Trials Centre

    Sheffield, S10 2SJ

  • Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit

    Sutton, SM2 5PT

  • Singleton Hospital; Pharmacy

    Swansea, SA2 8QA

Other trials in United Kingdom

Taiwan8 sites

  • Changhua Christian Hospital; Dept of Surgery

    Changhua, 500

  • Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

    Kaohsiung City, 807

  • China Medical University Hospital; Surgery

    Taichung, 404

  • Chi-Mei Medical Center

    Tainan, 736

  • VETERANS GENERAL HOSPITAL; Department of General Surgery

    Taipei, 00112

  • National Taiwan Uni Hospital; General Surgery

    Taipei, 100

  • Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology

    Taipei, 11259

  • Chang Gung Memorial Hospital - Linkou

    Taoyuan, 333

Other trials in Taiwan

Australia7 sites

  • Peter MacCallum Cancer Center

    East Melbourne, Victoria, 3002

  • Peninsula and South Eastern Haematology and Oncology Group

    Frankston, Victoria, 3199

  • St George Hospital; Cancer Care Centre

    Kogarah, New South Wales, 2217

  • Sunshine Hospital

    St Albans, Victoria, 3021

  • St John of God Hospital; Bendat Cancer Centre

    Subiaco, Western Australia, 6008

  • Calvary Mater Newcastle

    Waratah, New South Wales, 2298

  • Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

    Woolloongabba, Queensland, 4102

Other trials in Australia

Canada6 sites

  • McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology

    Montreal, Quebec, H3T 1E2

  • McGill University; Glen Site; Oncology

    Montreal, Quebec, H4A 3J1

  • Lakeridge Health Oshawa; Oncology

    Oshawa, Ontario, L1G 2B9

  • The Ottawa Hospital Cancer Centre; Oncology

    Ottawa, Ontario, K1H 8L6

  • Hopital du Saint Sacrement

    Québec, Quebec, G1S 4L8

  • Sunnybrook Odette Cancer Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

Germany6 sites

  • HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe

    Berlin, 13125

  • Studienzentrum Berlin City

    Berlin, 14169

  • Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum

    Essen, 45136

  • Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

    Freiburg im Breisgau, 79110

  • Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg

    Heidelberg, 69120

  • Institut für Versorgungsforschung in der Onkologie GbR Koblenz

    Koblenz, 56068

Other trials in Germany

Italy6 sites

  • Centro Di Riferimento Oncologico; SOC Oncologia Medica C

    Aviano, Friuli Venezia Giulia, 33081

  • A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2

    Bologna, Emilia-Romagna, 40138

  • Centro Catanese Di Oncologia; Oncologia Medica

    Catania, Sicily, 95126

  • IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

    Naples, Campania, 80131

  • Ospedale Regionale Di Parma; Divisione Di Oncologia Medica

    Parma, Emilia-Romagna, 43100

  • Ospedale Santo Stefano, Azienda USL Centro Prato

    Prato, Tuscany, 59100

Other trials in Italy

Spain6 sites

  • Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología

    A Coruña, 15006

  • Hospital Univ Vall d'Hebron; Servicio de Oncologia

    Barcelona, 08035

  • Hospital Universitario Reina Sofia; Servicio de Oncologia

    Córdoba, Cordoba, 14004

  • Hospital Ramon y Cajal; Servicio de Oncologia

    Madrid, 28034

  • Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

    Valencia, 46010

  • Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

    Valencia, 46015

Other trials in Spain

South Korea5 sites

  • National Cancer Center

    Goyang-si, 10408

  • Samsung Medical Center

    Seoul, (0)6351

  • Seoul National University Hospital

    Seoul, 03080

  • Severance Hospital, Yonsei University Health System

    Seoul, 03722

  • Asan Medical Center

    Seoul, 05505

Other trials in South Korea

About this study

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

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.

Being tested
Atezolizumab, Trastuzumab emtansine, Placebo
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Also called Tecentriq, RO5541267, MPDL3280A

    Atezolizumab 1200 mg IV infusion

  • Trastuzumab emtansineDrug

    Also called Kadcyla®, T-DM1, RO5304020

    Trastuzumab emtansine 3.6 mg/kg IV infusion

  • PlaceboOther

    Placebo matched to atezolizumab

Study groups in NCT02924883
Study groupRoleWhat they receive
Trastuzumab Emtansine + AtezolizumabExperimentalAtezolizumab 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)
Receives: Drug: Atezolizumab; Drug: Trastuzumab emtansine; Other: Placebo
Trastuzumab Emtansine + PlaceboActive comparatorPlacebo 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)
Receives: Drug: Trastuzumab emtansine; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  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)

    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.

    Measured: Baseline up to approximately 15 months

  2. Percentage of Participants With Adverse Events

    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.

    Measured: Baseline up to study completion, approximately 40 months

Secondary outcomes (9)

  1. Overall Survival (OS)

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

    Measured: Baseline up to study completion or death, whichever occurs first, approximately 40 months

  2. Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1

    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.

    Measured: Baseline up to approximately 15 months

  3. Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1

    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.

    Measured: Baseline up to approximately 15 months

  4. Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine

    Average post infusion Trastuzumab Emtansine concentration

    Measured: 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)

  5. Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)

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

    Measured: 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)

  6. Cmax of Total Trastuzumab

    Measured: 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

    Average post infusion atezolizumab concentration

    Measured: 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)

  8. Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab

    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).

    Measured: 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)

  9. Percentage of Participants With ATAs to Trastuzumab Emtansine

    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).

    Measured: 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)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Oct 2016 (estimated)
  2. Study start26 Sep 2016
  3. Primary completion11 Dec 2017
  4. Study completion6 Feb 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
202 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02924883
Sponsor's protocol ID
WO30085
Other IDs
2015-004189-27, 2015
Acronym
KATE2
Status last verified
Jan 2021
First submitted
21 Sep 2016
Last updated
17 Feb 2021

Publications

  • Emens LA, Esteva FJ, Beresford M, Saura C, De Laurentiis M, Kim SB, Im SA, Wang Y, Salgado R, Mani A, Shah J, Lambertini C, Liu H, de Haas SL, Patre M, Loi S. Trastuzumab emtansine plus atezolizumab versus trastuzumab emtansine plus placebo in previously treated, HER2-positive advanced breast cancer (KATE2): a phase 2, multicentre, randomised, double-blind trial. Lancet Oncol. 2020 Oct;21(10):1283-1295. doi: 10.1016/S1470-2045(20)30465-4.

    PubMed 33002436

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab and Trastuzumab emtansine in people with Metastatic Breast Cancer, run by Hoffmann-La Roche at 68 sites in 9 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 68 sites in United States, United Kingdom, Taiwan, Australia, Canada and 4 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Feb 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-Free Survival (PFS) as Determined by Investigator's Tumor Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) (time frame: Baseline up to approximately 15 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02924883, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2021.

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