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

Metastatic Breast Cancer Clinical Trial

— KATE2  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02924883
• Other study ID #: WO30085
• Secondary ID: 2015-004189-27
• Status: Completed
• Phase: Phase 2
• Start date: September 26, 2016
• Est. completion date: February 6, 2020

Study information

• Verified date: January 2021
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 based therapy, either alone or in combination, and/or who have progressed within 6 months after completing adjuvant therapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 202
• Est. completion date: February 6, 2020
• Est. primary completion date: December 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Metastatic Breast Cancer

Intervention

Drug:
• Atezolizumab
Atezolizumab 1200 mg IV infusion
• Trastuzumab emtansine
Trastuzumab emtansine 3.6 mg/kg IV infusion

Other:
• Placebo
Placebo matched to atezolizumab

Locations

Country	Name	City	State
Australia	Peter MacCallum Cancer Center	East Melbourne	Victoria
Australia	Peninsula and South Eastern Haematology and Oncology Group	Frankston	Victoria
Australia	St George Hospital; Cancer Care Centre	Kogarah	New South Wales
Australia	Sunshine Hospital	St Albans	Victoria
Australia	St John of God Hospital; Bendat Cancer Centre	Subiaco	Western Australia
Australia	Calvary Mater Newcastle	Waratah	New South Wales
Australia	Princess Alexandra Hospital Woolloongabba; Clinical Hematology and Medical Oncology	Woolloongabba	Queensland
Canada	McGill University; Glen Site; Oncology	Montreal	Quebec
Canada	McGill University; Sir Mortimer B Davis Jewish General Hospital; Oncology	Montreal	Quebec
Canada	Lakeridge Health Oshawa; Oncology	Oshawa	Ontario
Canada	The Ottawa Hospital Cancer Centre; Oncology	Ottawa	Ontario
Canada	Hopital du Saint Sacrement	Quebec City	Quebec
Canada	Sunnybrook Odette Cancer Centre	Toronto	Ontario
Germany	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
Germany	Nationales Centrum für Tumorerkrankungen (NCT) ; Gyn. Onk. Frauenklinik; Uniklinikum Heidelberg	Heidelberg
Germany	Institut für Versorgungsforschung in der Onkologie GbR Koblenz	Koblenz
Italy	Centro Di Riferimento Oncologico; SOC Oncologia Medica C	Aviano	Friuli-Venezia Giulia
Italy	A.O.U Policlinico S. Orsola Malpighi di Bologna U.O di Medicina Interna Borghi - Pad.2	Bologna	Emilia-Romagna
Italy	Centro Catanese Di Oncologia; Oncologia Medica	Catania	Sicilia
Italy	IRCCS Istituto Nazionale Tumori Fondazione Pascale; Oncologia Medica A	Napoli	Campania
Italy	Ospedale Regionale Di Parma; Divisione Di Oncologia Medica	Parma	Emilia-Romagna
Italy	Ospedale Santo Stefano, Azienda USL Centro Prato	Prato	Toscana
Korea, Republic of	National Cancer Center	Goyang-si
Korea, Republic of	Asan Medical Center	Seoul
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Seoul National University Hospital	Seoul
Korea, Republic of	Severance Hospital, Yonsei University Health System	Seoul
Spain	Hospital Univ Vall d'Hebron; Servicio de Oncologia	Barcelona
Spain	Hospital Universitario Reina Sofia; Servicio de Oncologia	Córdoba	Cordoba
Spain	Complejo Hospitalario Universitario A Coruña (CHUAC, Materno Infantil), Oncología	La Coruña
Spain	Hospital Ramon y Cajal; Servicio de Oncologia	Madrid
Spain	Hospital Arnau de Vilanova (Valencia) Servicio de Oncologia	Valencia
Spain	Hospital Clinico Universitario de Valencia; Servicio de Onco-hematologia	Valencia
Taiwan	Changhua Christian Hospital; Dept of Surgery	Changhua
Taiwan	Kaohsiung Medical Uni Chung-Ho Hospital; Dept of Surgery	Kaohsiung
Taiwan	China Medical University Hospital; Surgery	Taichung
Taiwan	Chi-Mei Medical Center	Tainan
Taiwan	National Taiwan Uni Hospital; General Surgery	Taipei
Taiwan	VETERANS GENERAL HOSPITAL; Department of General Surgery	Taipei
Taiwan	Koo Foundation Sun Yat-Sen Cancer Center; Hemato-Oncology	Taipei City
Taiwan	Chang Gung Memorial Hospital - Linkou	Taoyuan
United Kingdom	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 States	Northside Hospital	Atlanta	Georgia
United States	University of Colorado	Aurora	Colorado
United States	Johns Hopkins Univ Med Center	Baltimore	Maryland
United States	SCRI Tennessee Oncology Chattanooga	Chattanooga	Tennessee
United States	Ohio State Uni Medical Center	Columbus	Ohio
United States	San Juan Oncology Associates	Farmington	New Mexico
United States	SCRI Florida Cancer Specialists South	Fort Myers	Florida
United States	Tennessee Oncology; Sarah Cannon Research Institute	Nashville	Tennessee
United States	Laura and ISAAC Perlmutter Cancer Center at NYU Langone.	New York	New York
United States	Breastlink Med Group Inc	Orange	California
United States	Magee Womens Hospital	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists; Saint Petersburg	Saint Petersburg	Florida
United States	University of Washington	Seattle	Washington
United States	MedStar Georgetown University Hospital (Lombardi Comprehensive Cancer Center)	Washington	District of Columbia
United States	Cancer Care Associates of York	York	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

United States,  Australia,  Canada,  Germany,  Italy,  Korea, Republic of,  Spain,  Taiwan,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Overall Survival (OS)	OS was defined as the time from randomization to death from any cause.	Baseline up to study completion or death, whichever occurs first, approximately 40 months
Secondary	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.	Baseline up to approximately 15 months
Secondary	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.	Baseline up to approximately 15 months
Secondary	Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine	Average post infusion Trastuzumab Emtansine concentration	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)
Secondary	Cmax of Deacetyl Mercapto 1-Oxopropyl Maytansine (DM1)	Average post infusion Deacetyl Mercapto 1-Oxopropyl Maytansine concentration of trastuzumab emtansine infusion	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)
Secondary	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)
Secondary	Cmax of Atezolizumab	Average post infusion atezolizumab concentration	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)
Secondary	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).	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)
Secondary	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).	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)