Clinical trial NCT02924883: 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
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Metastatic Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2016-10-05
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
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)
timeFrame: Baseline up to approximately 15 months
measure: Percentage of Participants With Adverse Events
timeFrame: Baseline up to study completion, approximately 40 months
Secondary outcomes:
measure: Overall Survival (OS)
timeFrame: Baseline up to study completion or death, whichever occurs first, approximately 40 months
measure: Percentage of Participants With Objective Response (OR) as Determined by Investigator's Tumor Assessment Using RECIST v1.1
timeFrame: Baseline up to approximately 15 months
measure: Duration of OR as Determined by Investigator's Tumor Assessment Using RECIST v1.1
timeFrame: Baseline up to approximately 15 months
measure: Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine
timeFrame: 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)
measure: Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)
timeFrame: 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)
measure: Cmax of Total Trastuzumab
timeFrame: 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)
measure: Cmax of Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With Anti-therapeutic Antibodies (ATAs) to Atezolizumab
timeFrame: 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)
measure: Percentage of Participants With ATAs to Trastuzumab Emtansine
timeFrame: 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)
Other outcomes:
Locations:
city: Orange
country: United States
facility: Breastlink Med Group Inc
state: California
city: Aurora
country: United States
facility: University of Colorado
state: Colorado
city: Washington
country: United States
facility: MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)
state: District of Columbia
city: Fort Myers
country: United States
facility: SCRI Florida Cancer Specialists South
state: Florida
city: Saint Petersburg
country: United States
facility: Florida Cancer Specialists; Saint Petersburg
state: Florida
city: Atlanta
country: United States
facility: Northside Hospital
state: Georgia
city: Baltimore
country: United States
facility: Johns Hopkins Univ Med Center
state: Maryland
city: Farmington
country: United States
facility: San Juan Oncology Associates
state: New Mexico
city: New York
country: United States
facility: Laura and ISAAC Perlmutter Cancer Center at NYU Langone.
state: New York
city: Columbus
country: United States
facility: Ohio State Uni Medical Center
state: Ohio
city: Pittsburgh
country: United States
facility: Magee Womens Hospital
state: Pennsylvania
city: York
country: United States
facility: Cancer Care Associates of York
state: Pennsylvania
city: Chattanooga
country: United States
facility: SCRI Tennessee Oncology Chattanooga
state: Tennessee
city: Nashville
country: United States
facility: Tennessee Oncology; Sarah Cannon Research Institute
state: Tennessee
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Kogarah
country: Australia
facility: St George Hospital; Cancer Care Centre
state: New South Wales
city: Waratah
country: Australia
facility: Calvary Mater Newcastle
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology
state: Queensland
city: East Melbourne
country: Australia
facility: Peter MacCallum Cancer Center
state: Victoria
city: Frankston
country: Australia
facility: Peninsula and South Eastern Haematology and Oncology Group
state: Victoria
city: St Albans
country: Australia
facility: Sunshine Hospital
state: Victoria
city: Subiaco
country: Australia
facility: St John of God Hospital; Bendat Cancer Centre
state: Western Australia
city: Oshawa
country: Canada
facility: Lakeridge Health Oshawa; Oncology
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre; Oncology
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Odette Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology
state: Quebec
city: Montreal
country: Canada
facility: McGill University; Glen Site; Oncology
state: Quebec
city: Quebec City
country: Canada
facility: Hopital du Saint Sacrement
state: Quebec
city: Berlin
country: Germany
facility: HELIOS Klinikum Berlin-Buch; Klinik für Gynäkologie und Geburtshilfe
city: Berlin
country: Germany
facility: Studienzentrum Berlin City
city: Essen
country: Germany
facility: Klinikum Essen-Mitte Ev. Huyssens-Stiftung / Knappschafts GmbH; Klinik für Senologie / Brustzentrum
city: Freiburg
country: Germany
facility: Praxis für Interdisziplinäre Onkologie und Hämatologie GbR
city: Heidelberg
country: Germany
facility: Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg
city: Koblenz
country: Germany
facility: Institut für Versorgungsforschung in der Onkologie GbR Koblenz
city: Napoli
country: Italy
facility: IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A
state: Campania
city: Bologna
country: Italy
facility: A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2
state: Emilia-Romagna
city: Parma
country: Italy
facility: Ospedale Regionale Di Parma; Divisione Di Oncologia Medica
state: Emilia-Romagna
city: Aviano
country: Italy
facility: Centro Di Riferimento Oncologico; SOC Oncologia Medica C
state: Friuli-Venezia Giulia
city: Catania
country: Italy
facility: Centro Catanese Di Oncologia; Oncologia Medica
state: Sicilia
city: Prato
country: Italy
facility: Ospedale Santo Stefano, Azienda USL Centro Prato
state: Toscana
city: Goyang-si
country: Korea, Republic of
facility: National Cancer Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital, Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia; Servicio de Oncologia
state: Cordoba
city: Barcelona
country: Spain
facility: Hospital Univ Vall d'Hebron; Servicio de Oncologia
city: La Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología
city: Madrid
country: Spain
facility: Hospital Ramon y Cajal; Servicio de Oncologia
city: Valencia
country: Spain
facility: Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia
city: Changhua
country: Taiwan
facility: Changhua Christian Hospital; Dept of Surgery
city: Kaohsiung
country: Taiwan
facility: Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery
city: Taichung
country: Taiwan
facility: China Medical University Hospital; Surgery
city: Tainan
country: Taiwan
facility: Chi-Mei Medical Center
city: Taipei City
country: Taiwan
facility: Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology
city: Taipei
country: Taiwan
facility: VETERANS GENERAL HOSPITAL; Department of General Surgery
city: Taipei
country: Taiwan
facility: National Taiwan Uni Hospital; General Surgery
city: Taoyuan
country: Taiwan
facility: Chang Gung Memorial Hospital - Linkou
city: Bath
country: United Kingdom
facility: Royal United Hospital; Oncology Department
city: Glasgow
country: United Kingdom
facility: Beatson West of Scotland Cancer Centre
city: London
country: United Kingdom
facility: Royal Free Hospital; Dept of Oncology
city: London
country: United Kingdom
facility: Royal Marsden Hosp NHS Fnd; Breast Unit
city: Manchester
country: United Kingdom
facility: Christie Hospital; Breast Cancer Research Office
city: Nottingham
country: United Kingdom
facility: Nottingham City Hospital
city: Sheffield
country: United Kingdom
facility: Weston Park Hospital; Cancer Clinical Trials Centre
city: Sutton
country: United Kingdom
facility: Royal Marsden Hosp NHS Fnd; Medicine - Breast Unit
city: Swansea
country: United Kingdom
facility: Singleton Hospital; Pharmacy
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References:
citation: 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.