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

NCT02924883 | Completed Phase 2 Results

• 2 other identifiers: WO300852015-004189-27
• Study Type: interventional
• Target: 202
• Locations: 9 countries
• Sites: 68

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

Outcome Measures

Primary Outcomes (2)

• 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.

  Baseline up to approximately 15 months

• 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.

  Baseline up to study completion, approximately 40 months

Secondary Outcomes (9)

• Overall Survival (OS)

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

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

  Baseline up to approximately 15 months

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

  Baseline up to approximately 15 months

• 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)

• 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)

Study Arms (2)

Trastuzumab Emtansine + Atezolizumab

EXPERIMENTAL

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; Drug: Trastuzumab emtansine; Other: Placebo

Trastuzumab Emtansine + Placebo

ACTIVE COMPARATOR

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; Other: Placebo

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg IV infusion

Also known as: Tecentriq, RO5541267, MPDL3280A

Trastuzumab Emtansine + Atezolizumab

Trastuzumab emtansine DRUG

Trastuzumab emtansine 3.6 mg/kg IV infusion

Also known as: Kadcyla®, T-DM1, RO5304020

Trastuzumab Emtansine + Atezolizumab; Trastuzumab Emtansine + Placebo

Placebo OTHER

Placebo matched to atezolizumab

Trastuzumab Emtansine + Atezolizumab; Trastuzumab Emtansine + Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (68)

Breastlink Med Group Inc

Orange, California, 92868, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)

Washington D.C., District of Columbia, 20007, United States

Location

SCRI Florida Cancer Specialists South

Fort Myers, Florida, 33916, United States

Location

Florida Cancer Specialists; Saint Petersburg

St. Petersburg, Florida, 33719, United States

Location

Northside Hospital

Atlanta, Georgia, 30342, United States

Location

Johns Hopkins Univ Med Center

Baltimore, Maryland, 21231, United States

Location

San Juan Oncology Associates

Farmington, New Mexico, 87401, United States

Location

Laura and ISAAC Perlmutter Cancer Center at NYU Langone.

New York, New York, 10016, United States

Location

Ohio State Uni Medical Center

Columbus, Ohio, 43210, United States

Location

Magee Womens Hospital

Pittsburgh, Pennsylvania, 15213, United States

Location

Cancer Care Associates of York

York, Pennsylvania, 17403, United States

Location

SCRI Tennessee Oncology Chattanooga

Chattanooga, Tennessee, 37404, United States

Location

Tennessee Oncology; Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

University of Washington

Seattle, Washington, 98195, United States

Location

St George Hospital; Cancer Care Centre

Kogarah, New South Wales, 2217, Australia

Location

Calvary Mater Newcastle

Waratah, New South Wales, 2298, Australia

Location

Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology

Woolloongabba, Queensland, 4102, Australia

Location

Peter MacCallum Cancer Center

East Melbourne, Victoria, 3002, Australia

Location

Peninsula and South Eastern Haematology and Oncology Group

Frankston, Victoria, 3199, Australia

Location

Sunshine Hospital

St Albans, Victoria, 3021, Australia

Location

St John of God Hospital; Bendat Cancer Centre

Subiaco, Western Australia, 6008, Australia

Location

Lakeridge Health Oshawa; Oncology

Oshawa, Ontario, L1G 2B9, Canada

Location

The Ottawa Hospital Cancer Centre; Oncology

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Odette Cancer Centre

Toronto, Ontario, M4N 3M5, Canada

Location

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

Montreal, Quebec, H3T 1E2, Canada

Location

McGill University; Glen Site; Oncology

Montreal, Quebec, H4A 3J1, Canada

Location

Hopital du Saint Sacrement

Québec, Quebec, G1S 4L8, Canada

Location

HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe

Berlin, 13125, Germany

Location

Studienzentrum Berlin City

Berlin, 14169, Germany

Location

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

Essen, 45136, Germany

Location

Praxis für Interdisziplinäre Onkologie und Hämatologie GbR

Freiburg im Breisgau, 79110, Germany

Location

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

Heidelberg, 69120, Germany

Location

Institut für Versorgungsforschung in der Onkologie GbR Koblenz

Koblenz, 56068, Germany

Location

IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A

Napoli, Campania, 80131, Italy

Location

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

Bologna, Emilia-Romagna, 40138, Italy

Location

Ospedale Regionale Di Parma; Divisione Di Oncologia Medica

Parma, Emilia-Romagna, 43100, Italy

Location

Centro Di Riferimento Oncologico; SOC Oncologia Medica C

Aviano, Friuli Venezia Giulia, 33081, Italy

Location

Centro Catanese Di Oncologia; Oncologia Medica

Catania, Sicily, 95126, Italy

Location

Ospedale Santo Stefano, Azienda USL Centro Prato

Prato, Tuscany, 59100, Italy

Location

National Cancer Center

Goyang-si, 10408, South Korea

Location

Samsung Medical Center

Seoul, (0)6351, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Hospital Universitario Reina Sofia; Servicio de Oncologia

Córdoba, Cordoba, 14004, Spain

Location

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

A Coruña, 15006, Spain

Location

Hospital Univ Vall d'Hebron; Servicio de Oncologia

Barcelona, 08035, Spain

Location

Hospital Ramon y Cajal; Servicio de Oncologia

Madrid, 28034, Spain

Location

Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia

Valencia, 46010, Spain

Location

Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia

Valencia, 46015, Spain

Location

Changhua Christian Hospital; Dept of Surgery

Changhua, 500, Taiwan

Location

Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery

Kaohsiung City, 807, Taiwan

Location

China Medical University Hospital; Surgery

Taichung, 404, Taiwan

Location

Chi-Mei Medical Center

Tainan, 736, Taiwan

Location

VETERANS GENERAL HOSPITAL; Department of General Surgery

Taipei, 00112, Taiwan

Location

National Taiwan Uni Hospital; General Surgery

Taipei, 100, Taiwan

Location

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

Taipei, 11259, Taiwan

Location

Chang Gung Memorial Hospital - Linkou

Taoyuan District, 333, Taiwan

Location

Royal United Hospital; Oncology Department

Bath, BA1 3NG, United Kingdom

Location

Beatson West of Scotland Cancer Centre

Glasgow, G12 0YN, United Kingdom

Location

Royal Free Hospital; Dept of Oncology

London, NW3 2QG, United Kingdom

Location

Royal Marsden Hosp NHS Fnd; Breast Unit

London, SW3 6JJ, United Kingdom

Location

Christie Hospital; Breast Cancer Research Office

Manchester, M20 4QL, United Kingdom

Location

Nottingham City Hospital

Nottingham, NG5 1PB, United Kingdom

Location

Weston Park Hospital; Cancer Clinical Trials Centre

Sheffield, S10 2SJ, United Kingdom

Location

Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit

Sutton, SM2 5PT, United Kingdom

Location

Singleton Hospital; Pharmacy

Swansea, SA2 8QA, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 33002436 DERIVED

MeSH Terms

Conditions

Breast Neoplasms

Interventions

atezolizumab; Ado-Trastuzumab Emtansine

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Maytansine; Macrolides; Lactones; Organic Chemicals; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Trastuzumab; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800 821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2016
• First Posted: October 5, 2016
• Study Start: September 26, 2016
• Primary Completion: December 11, 2017
• Study Completion: February 6, 2020
• Last Updated: February 17, 2021
• Results First Posted: February 12, 2019

Record last verified: 2021-01

Locations

GB (9); DE (6); US (15); IT (6); CA (6); KR (5); ES (6); AU (7); TW (8)