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)

NCT04740918 | Terminated Phase 3 Results DMC FDA Drug

• 2 other identifiers: MO423192020-002818-41
• Study Type: interventional
• Target: 96
• Locations: 19 countries
• Sites: 51

Brief Summary

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.

Conditions

Metastatic Breast Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (7)

• Objective Response Rate (ORR)

  Up to 28 months

• Duration of Response (DOR)

  Up to 28 months

• PFS in Participants With Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1

  Up to 28 months

• OS in Participants With Baseline Brain Metastases

  Up to 28 months

• Central Nervous System (CNS) PFS as Determined by Investigator Using RECIST v1.1 in Participants With Baseline CNS Metastases

  Up to 28 months

Other Outcomes (8)

• PFS as Determined by a Blinded Independent Central Review (BICR) Committee Using RECIST v1.1

  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)

  Up to 28 months

• Change From-Baseline in PF, RF and GHS/QoL Scores Measured Using EORTC QLQ-C30

  Up to 28 months

Study Arms (2)

Arm A: Trastuzumab Emtansine and Placebo

ACTIVE COMPARATOR

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; Other: Placebo

Arm B: Trastuzumab Emtansine and Atezolizumab

EXPERIMENTAL

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; Drug: Atezolizumab

Interventions

Trastuzumab Emtansine DRUG

Trastuzumab emtansine 3.6 mg/kg IV infusion

Also known as: Kadcyla, T-DM1, RO5304020

Arm A: Trastuzumab Emtansine and Placebo; Arm B: Trastuzumab Emtansine and Atezolizumab

Atezolizumab DRUG

Atezolizumab 1200 mg IV infusion

Also known as: Tecentriq, RO5541267, MPDL3280A

Arm B: Trastuzumab Emtansine and Atezolizumab

Placebo OTHER

Placebo matched to atezolizumab

Arm A: Trastuzumab Emtansine and Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (51)

Emad Ibrahim, Md, Inc

Redlands, California, 92373, United States

Location

Peter MacCallum Cancer Center

Melbourne, Victoria, 3000, Australia

Location

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, 41253-190, Brazil

Location

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, 50040-000, Brazil

Location

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, 98700-000, Brazil

Location

Hospital de Base de Sao Jose do Rio Preto

São José do Rio Preto, São Paulo, 15090-000, Brazil

Location

Núcleo de Pesquisa São Camilo

São Paulo, São Paulo, 03102-002, Brazil

Location

Royal Victoria Hospital

Barrie, Ontario, L4M 6M2, Canada

Location

Centre Hospitalier de l?Université de Montréal (CHUM)

Montreal, Quebec, H2X 0C2, Canada

Location

Peking University People's Hospital

Beijing, 100044, China

Location

Beijing Cancer Hospital

Beijing, 100142, China

Location

The First Hospital of Jilin University

Changchun, 130021, China

Location

Sun Yat-sen Memorial Hospital, Sun Yat-sen University

Guangzhou, 510120, China

Location

Zhejiang Provincial People's Hospital

Hangzhou, 310014, China

Location

Harbin Medical University Cancer Hospital

Harbin, 150081, China

Location

Jiangsu Province Hospital (the First Affiliated Hospital With Nanjing Medical University)

Nanjing, 210029, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjing, 300060, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, 430023, China

Location

Henan Cancer Hospital

Zhengzhou, 450008, China

Location

Clinica Vida

Medellín, DUMMY_VALUE, Colombia

Location

Oncomedica S.A.

Montería, 230002, Colombia

Location

Clinical Hospital Center Sestre Milosrdnice

Zagreb, 10000, Croatia

Location

Clinical Hospital Centre Zagreb

Zagreb, 10000, Croatia

Location

Helsinki University Central Hospital

Helsinki, 00029, Finland

Location

Tampere University Hospital

Tampere, 33520, Finland

Location

Institut Curie - Hopital Rene Huguenin

Saint-Cloud, 92211, France

Location

Azienda Ospedaliera di Rilievo Nazionale e di Alta Specialita San Giuseppe Moscati

Avellino, Campania, 83100, Italy

Location

Istituto Nazionale Tumori Irccs Fondazione g. PASCALE

Napoli, Campania, 80131, Italy

Location

Azienda Ospedaliera S. Orsola-Malpighi

Bologna, Emilia-Romagna, 40138, Italy

Location

Oslo Universitetssykehus HF

Oslo, 0450, Norway

Location

Cebu Doctors' University Hospital

Cebu City, 6000, Philippines

Location

St. Luke's Medical Center

Quezon City, 1102, Philippines

Location

Cardinal Santos Medical Center

San Juan City, 1502, Philippines

Location

Opolskie Centrum Onkologii

Opole, 45-061, Poland

Location

Centrum Onkologii ? Instytut im. Marii Sk?odowskiej-Curie Klinika Nowotworów Piersi i Chirurgii

Warsaw, 02-781, Poland

Location

Centro Hospitalar do Porto ? Hospital de Santo António

Porto, 4099-001, Portugal

Location

IPO do Porto

Porto, 4200-072, Portugal

Location

SBIH Republican Clinical Oncological Dispensary of the MoH of Republic Bashkortostan

Ufa, Bashkortostan Republic, 450054, Russia

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Hospital Universitario Quiron Madrid

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Hospital Universitario La Paz

Madrid, 28046, Spain

Location

Adana Baskent University Medical Faculty

Adana, 01220, Turkey (Türkiye)

Location

Sakarya Universitesi Egitim ve Arastirma Hastanesi

Adapazari/Sakarya, 54100, Turkey (Türkiye)

Location

Bakirkoy Dr. Sadi Konuk Egitim ve Arastirma Hastanesi, Tibbi Onkoloji

Bakirkoy / Istanbul, 34147, Turkey (Türkiye)

Location

Acibadem University School of Medicine Altunizade Hospital Oncology Service

Istanbul, 34742, Turkey (Türkiye)

Location

Katip Celebi University Ataturk Training and Research Hospital

Izmir, 35360, Turkey (Türkiye)

Location

Kayseri Acibadem Hospital

Kayseri, 38000, Turkey (Türkiye)

Location

Hacettepe Uni Medical Faculty Hospital

Sihhiye/Ankara, 06230, Turkey (Türkiye)

Location

UCL Hospital NHS Trust

London, NW1 2PG, United Kingdom

Location

Guys and St Thomas NHS Foundation Trust, Guys Hospital

London, SE1 9RT, United Kingdom

Location

Nottingham University Hospitals City Campus

Nottingham, NG5 1PB, United Kingdom

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Ado-Trastuzumab Emtansine; atezolizumab

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

Limitations and Caveats

The Sponsor decided to prematurely terminate the study due to a lower-than-expected enrollment rate.

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 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 3, 2021
• First Posted: February 5, 2021
• Study Start: June 7, 2021
• Primary Completion: June 19, 2024
• Study Completion: June 19, 2024
• Last Updated: August 8, 2025
• Results First Posted: August 8, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share

Locations

GB (3); PT (2); AU (1); CN (10); FR (1); KR (1); PH (3); IT (3); BR (5); US (1); CR (2); NO (1); FI (2); ES (2); CA (2); CO (2); RU (1); TU (7); PL (2)