A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC) (KATE3)

A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo in Patients With HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3)

This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.

Study Overview

• Status: Terminated
• Conditions: Metastatic Breast Cancer
• Intervention / Treatment: Drug: Trastuzumab Emtansine; Other: Placebo; Drug: Atezolizumab

• Study Type: Interventional
• Enrollment (Actual): 96
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Peter MacCallum Cancer Center
• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 41253-190
      • Hospital Sao Rafael - HSR
  • Pernambuco
    • Recife, Pernambuco, Brazil, 50040-000
      • Hospital do Cancer de Pernambuco - HCP
  • Rio Grande Do Sul
    • Ijui, Rio Grande Do Sul, Brazil, 98700-000
      • ONCOSITE - Centro de Pesquisa Clinica em Oncologia LTDA
  • São Paulo
    • Sao Jose do Rio Preto, São Paulo, Brazil, 15090-000
      • Hospital de Base de Sao Jose do Rio Preto
    • Sao Paulo, São Paulo, Brazil, 03102-002
      • Núcleo de Pesquisa São Camilo
• Canada
  • Ontario
    • Barrie, Ontario, Canada, L4M 6M2
      • Royal Victoria Hospital
  • Quebec
    • Montreal, Quebec, Canada, H2X 0C2
      • Centre Hospitalier de l?Université de Montréal (CHUM)
• China
  • Beijing, China, 100142
    • Beijing Cancer Hospital
  • Beijing, China, 100044
    • Peking University People's Hospital
  • Changchun City, China, 130021
    • The First Hospital of Jilin University
  • Guangzhou City, China, 510120
    • Sun Yat-sen Memorial Hospital, Sun Yat-sen University
  • Hangzhou, China, 310014
    • Zhejiang Provincial People's Hospital
  • Harbin, China, 150081
    • Harbin Medical University Cancer Hospital
  • Nanjing City, China, 210029
    • Jiangsu Province Hospital (The First Affiliated Hospital with Nanjing Medical University)
  • Tianjing, China, 300060
    • Tianjin Medical University Cancer Institute & Hospital
  • Wuhan City, China, 430023
    • Union Hospital Tongji Medical College Huazhong University of Science and Technology
  • Zhengzhou, China, 450008
    • Henan Cancer Hospital
• Colombia
  • Medellin, Colombia, DUMMY_VALUE
    • Clinica Vida
  • Monteria, Colombia, 230002
    • Oncomedica S.A.
• Croatia
  • Zagreb, Croatia, 10000
    • Clinical Hospital Centre Zagreb
  • Zagreb, Croatia, 10000
    • Clinical Hospital Center Sestre Milosrdnice
• Finland
  • Helsinki, Finland, 00029
    • Helsinki University Central Hospital
  • Tampere, Finland, 33520
    • Tampere University Hospital
• France
  • Saint-Cloud, France, 92211
    • Institut Curie - Hôpital René Huguenin
• Italy
  • Campania
    • Avellino, Campania, Italy, 83100
      • Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati
    • Napoli, Campania, Italy, 80131
      • Istituto Nazionale Tumori Irccs Fondazione g. Pascale
  • Emilia-Romagna
    • Bologna, Emilia-Romagna, Italy, 40138
      • Azienda Ospedaliera S. Orsola-Malpighi
• Korea, Republic of
  • Seoul, Korea, Republic of, 03080
    • Seoul National University Hospital
• Norway
  • Oslo, Norway, 0450
    • Oslo Universitetssykehus HF
• Philippines
  • Cebu City, Philippines, 6000
    • Cebu Doctors' University Hospital
  • Quezon City, Philippines, 1102
    • St. Luke's Medical Center
  • San Juan, Philippines, 1502
    • Cardinal Santos Medical Center
• Poland
  • Opole, Poland, 45-061
    • Opolskie Centrum Onkologii
  • Warszawa, Poland, 02-781
    • Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii
• Portugal
  • Porto, Portugal, 4200-072
    • IPO do Porto
  • Porto, Portugal, 4099-001
    • Centro Hospitalar do Porto ? Hospital de Santo António
• Russian Federation
  • Baskortostan
    • Ufa, Baskortostan, Russian Federation, 450054
      • SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan
• Spain
  • Madrid, Spain, 28046
    • Hospital Universitario La Paz
  • Madrid
    • Pozuelo de Alarcón, Madrid, Spain, 28223
      • Hospital Universitario Quiron Madrid
• Turkey
  • Adana, Turkey, 01220
    • Adana Baskent University Medical Faculty
  • Adapazari/Sakarya, Turkey, 54100
    • Sakarya Universitesi Egitim ve Arastirma Hastanesi
  • Bakirkoy / Istanbul, Turkey, 34147
    • Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji
  • Istanbul, Turkey, 34742
    • Acibadem University School of Medicine Altunizade Hospital Oncology Service
  • Izmir, Turkey, 35360
    • Katip Celebi University Ataturk Training and Research Hospital
  • Kayseri, Turkey, 38000
    • Kayseri Acibadem Hospital
  • Sihhiye/Ankara, Turkey, 06230
    • Hacettepe Uni Medical Faculty Hospital
• United Kingdom
  • London, United Kingdom, SE1 9RT
    • Guys and St Thomas NHS Foundation Trust, Guys Hospital
  • London, United Kingdom, NW1 2PG
    • UCL Hospital NHS Trust
  • Nottingham, United Kingdom, NG5 1PB
    • Nottingham University Hospitals City Campus
• United States
  • California
    • Redlands, California, United States, 92373
      • Emad Ibrahim, MD, INC

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC)
• Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy
• Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting
• No more than two prior lines of therapy in the metastatic setting
• Measurable disease per RESIST version 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
• Life expectancy >= 6 months
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs
• For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm

Exclusion Criteria:

• Prior treatment with trastuzumab emtansine in metastatic setting
• History of exposure to cumulative doses of anthracyclines
• Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible
• Current Grade >= 3 peripheral neuropathy
• Cardiopulmonary dysfunction
• History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death
• History of leptomeningeal disease
• Active or history of autoimmune disease or immune deficiency
• Active hepatitis B, hepatitis C and/or tuberculosis
• Prior allogeneic stem cell or solid organ transplantation
• Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment
• Pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arm A: Trastuzumab Emtansine and Placebo; Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (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.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020; Other: Placebo; Placebo matched to atezolizumab
Experimental: Arm B: Trastuzumab Emtansine and Atezolizumab; Atezolizumab 1200 mg IV infusion 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.	Drug: Trastuzumab Emtansine; Trastuzumab emtansine 3.6 mg/kg IV infusion; Other Names: Kadcyla, T-DM1, RO5304020; Drug: Atezolizumab; Atezolizumab 1200 mg IV infusion; Other Names: Tecentriq, RO5541267, MPDL3280A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)	PFS was defined as the time from randomization to the first occurrence of documented disease progression (PD), as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Median PFS was calculated using the Kaplan-Meier (KM) methodology. Data for participants without PD or death from any cause as of the data cut-off date were censored at the time of the last tumor assessment.	Up to 28 months
Overall Survival (OS)	OS was defined as the time from the first dose of study treatment to the time of death from any cause. Participants who are alive as of the data cut-off date of the analysis were censored at the last known date they were alive. Participants with no post-baseline information were censored at the date of randomization plus 1 day. Median OS was calculated using the KM methodology.	Up to 28 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate (ORR)	ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) on two consecutive assessments, at least 28 days apart, as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. Only participants with measurable disease at baseline were analyzed for this outcome measure. Participants without a post-baseline tumor assessment were considered non-responders. An estimate of the ORR and its 95% CI (Wilson score confidence interval) were calculated for each treatment arm.	Up to 28 months
Duration of Response (DOR)	DOR was calculated for participants who had a best OR of CR/PR. DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to <10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median DOR was calculated using the KM methodology.	Up to 28 months
PFS in Participants With Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1	PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology.	Up to 28 months
OS in Participants With Baseline Brain Metastases	OS is defined as the time from the first dose of study treatment to the time of death from any cause. Median OS was calculated using the KM methodology.	Up to 28 months
Central Nervous System (CNS) PFS as Determined by Investigator Using RECIST v1.1 in Participants With Baseline CNS Metastases	CNS PFS was defined as the time from randomization to the first occurrence of documented CNS PD, or first occurrence of symptomatic CNS disease as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology. Participants who experienced non-CNS PD at the time of analysis were censored at the date of this progression. Participants who experienced no PD and were alive at the time of analysis were censored at date of their last post-baseline tumor assessment or, if they had no post-baseline tumor assessment, on the date of randomization + 1 day.	Up to 28 months
CNS PFS as Determined by Investigator Using RECIST v1.1 in Participants Without Baseline CNS Metastases	CNS PFS was defined as the time from randomization to the first occurrence of documented CNS PD, or first occurrence of symptomatic CNS disease as determined by the investigator according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology. Participants who experienced non-CNS PD at the time of analysis were censored at the date of this progression. Participants who experienced no PD and were alive at the time of analysis were censored at date of their last post-baseline tumor assessment or, if they had no post-baseline tumor assessment, on the date of randomization + 1 day.	Up to 28 months
Percentage of Participants With Adverse Events (AEs)	An AE was 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 AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.	Up to 28 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
PFS as Determined by a Blinded Independent Central Review (BICR) Committee Using RECIST v1.1	PFS was defined as the time from randomization to the first occurrence of documented PD, as determined by the BICR committee according to RECIST v1.1 or death from any cause whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.	Up to 28 months
Mean Absolute Scores in Physical Function (PF), Role Function (RF) and Global Health Status (GHS/QoL) Scores Measured Using European Organization for Research and Treatment of Cancer (EORTC QLQ-C30)	EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.	Up to 28 months
Change From-Baseline in PF, RF and GHS/QoL Scores Measured Using EORTC QLQ-C30	EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.	Up to 28 months
Percentage of Participants With Clinically Meaningful Deterioration in PF, RF and GHS/QoL Measured Using EORTC QLQ-C30	EORTC QLQ-C30 consists of 30 questions that assess five aspects of participant functioning (physical, emotional, role, cognitive, and social), three symptom scales (fatigue, nausea and vomiting, pain), GHS/QoL, and six single items (dyspnea, insomnia, appetite loss, constipation, diarrhea, and financial difficulties). The PF scale has 5 questions about participant's PF and daily activities (strenuous activities, long walks, short walks, bed/chair rest & needing help with eating, dressing, washing themselves, or using the toilet). The RF scale has 2 questions about work/daily activities and hobbies/leisurely activities. The PF and RF are scored on a 4-point scale (1=Not at All to 4=Very Much). The GHS/QoL are scored on a 7-point scale (1=Very Poor to 7=Excellent). The obtained scores are linearly transformed to a score range of 0-100, where higher scores indicate a higher response level and better QoL, functioning/support.	Up to 28 months
Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine	As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.	Up to 28 months
Cmax of Atezolizumab	As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, PK objectives and outcome measures were no longer applicable. Hence sample collection was stopped, and this outcome measure was not assessed or analyzed.	Up to 28 months
Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine	As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.	Up to 28 months
Percentage of Participants With ADAs to Atezolizumab	As prespecified in the latest protocol, following sponsor's decision to prematurely terminate the study, immunogenicity objectives and outcome measures were no longer applicable.	Up to 28 months

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche
• Investigators: Study Director: Clinical Trials, Hoffmann-La Roche

Study record dates

Study Major Dates

• Study Start (Actual): June 7, 2021
• Primary Completion (Actual): June 19, 2024
• Study Completion (Actual): June 19, 2024

Study Registration Dates

• First Submitted: February 3, 2021
• First Submitted That Met QC Criteria: February 3, 2021
• First Posted (Actual): February 5, 2021

Study Record Updates

• Last Update Posted (Actual): August 8, 2025
• Last Update Submitted That Met QC Criteria: July 22, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Skin Diseases; Breast Diseases; Breast Neoplasms; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Immunologic Factors; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Immunoconjugates; Immunotoxins; Trastuzumab; Atezolizumab; Ado-Trastuzumab Emtansine; Maytansine
• Other Study ID Numbers: MO42319; 2020-002818-41 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: For eligible studies, qualified researchers may request access to individual patient level clinical data. See Roche's commitment to transparency of clinical study information here: https://go.roche.com/data_sharing

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No