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

NCT ID: NCT02924883

Last Updated: 2021-02-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 202 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-26
• Study Completion Date: 2020-02-06

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.

Conditions

Metastatic Breast Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

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)

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 mg IV infusion

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg IV infusion

Placebo

Intervention Type: OTHER

Placebo matched to atezolizumab

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)

Group Type: ACTIVE_COMPARATOR

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg IV infusion

Placebo

Intervention Type: OTHER

Placebo matched to atezolizumab

Interventions

Atezolizumab

Atezolizumab 1200 mg IV infusion

Intervention Type: DRUG

Trastuzumab emtansine

Trastuzumab emtansine 3.6 mg/kg IV infusion

Intervention Type: DRUG

Placebo

Placebo matched to atezolizumab

Intervention Type: OTHER

Other Intervention Names

Tecentriq, RO5541267, MPDL3280A; Kadcyla®, T-DM1, RO5304020

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

Breastlink Med Group Inc

Orange, California, United States

University of Colorado

Aurora, Colorado, United States

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Washington D.C., District of Columbia, United States

SCRI Florida Cancer Specialists South

Fort Myers, Florida, United States

Florida Cancer Specialists; Saint Petersburg

St. Petersburg, Florida, United States

Northside Hospital

Atlanta, Georgia, United States

Johns Hopkins Univ Med Center

Baltimore, Maryland, United States

San Juan Oncology Associates

Farmington, New Mexico, United States

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, United States

Ohio State Uni Medical Center

Columbus, Ohio, United States

Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Cancer Care Associates of York

York, Pennsylvania, United States

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, United States

Tennessee Oncology; Sarah Cannon Research Institute

Nashville, Tennessee, United States

University of Washington

Seattle, Washington, United States

St George Hospital; Cancer Care Centre

Kogarah, New South Wales, Australia

Calvary Mater Newcastle

Waratah, New South Wales, Australia

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

Woolloongabba, Queensland, Australia

Peter MacCallum Cancer Center

East Melbourne, Victoria, Australia

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, Australia

Sunshine Hospital

St Albans, Victoria, Australia

St John of God Hospital; Bendat Cancer Centre

Subiaco, Western Australia, Australia

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, Canada

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, Canada

Sunnybrook Odette Cancer Centre

Toronto, Ontario, Canada

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

Montreal, Quebec, Canada

McGill University; Glen Site; Oncology

Montreal, Quebec, Canada

Hopital du Saint Sacrement

Québec, Quebec, Canada

HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe

Berlin, , Germany

Studienzentrum Berlin City

Berlin, , Germany

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

Essen, , Germany

Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

Freiburg im Breisgau, , Germany

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

Heidelberg, , Germany

Institut für Versorgungsforschung in der Onkologie GbR Koblenz

Koblenz, , Germany

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

Napoli, Campania, Italy

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

Bologna, Emilia-Romagna, Italy

Ospedale Regionale Di Parma; Divisione Di Oncologia Medica

Parma, Emilia-Romagna, Italy

Centro Di Riferimento Oncologico; SOC Oncologia Medica C

Aviano, Friuli Venezia Giulia, Italy

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicily, Italy

Ospedale Santo Stefano, Azienda USL Centro Prato

Prato, Tuscany, Italy

National Cancer Center

Goyang-si, , South Korea

Samsung Medical Center

Seoul, , South Korea

Seoul National University Hospital

Seoul, , South Korea

Severance Hospital, Yonsei University Health System

Seoul, , South Korea

Asan Medical Center

Seoul, , South Korea

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, Spain

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

A Coruña, , Spain

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, , Spain

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, , Spain

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, , Spain

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, , Spain

Changhua Christian Hospital; Dept of Surgery

Changhua, , Taiwan

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung City, , Taiwan

China Medical University Hospital; Surgery

Taichung, , Taiwan

Chi-Mei Medical Center

Tainan City, , Taiwan

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, , Taiwan

National Taiwan Uni Hospital; General Surgery

Taipei, , Taiwan

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

Taipei, , Taiwan

Chang Gung Memorial Hospital - Linkou

Taoyuan District, , Taiwan

Royal United Hospital; Oncology Department

Bath, , United Kingdom

Beatson West of Scotland Cancer Centre

Glasgow, , United Kingdom

Royal Free Hospital; Dept of Oncology

London, , United Kingdom

Royal Marsden Hosp NHS Fnd; Breast Unit

London, , United Kingdom

Christie Hospital; Breast Cancer Research Office

Manchester, , United Kingdom

Nottingham City Hospital

Nottingham, , United Kingdom

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, , United Kingdom

Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit

Sutton, , United Kingdom

Singleton Hospital; Pharmacy

Swansea, , United Kingdom

Countries

United States; Australia; Canada; Germany; Italy; South Korea; Spain; Taiwan; United Kingdom

References

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.

Reference Type: DERIVED

PMID: 33002436 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2015-004189-27

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

WO30085

Identifier Type: -

Identifier Source: org_study_id