A Study of Atezolizumab Plus Nab-Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic PD-L1-Positive Triple-Negative Breast Cancer

NCT ID: NCT04148911

Last Updated: 2025-12-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 184 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-12-10
• Study Completion Date: 2024-12-15

Brief Summary

Study MO39874 is an open-label, Phase IIIb, single arm, global study conducted in participants with unresectable locally advanced or metastatic PD-L1-positive Triple-Negative Breast Cancer (TNBC) who have not received chemotherapy for their unresectable locally advanced or metastatic disease.

Conditions

Triple-Negative Breast Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Atezolizumab plus Nab-Paclitaxel

Participants will receive Atezolizumab via intravenous (IV) infusion on Days 1 and 15 of every 28-day cycle in combination with Nab-Paclitaxel on Days 1, 8, and 15 (individually selected by the investigator) until disease progression, or unacceptable toxicity, additionally until loss of clinical benefit as determined by the investigator or participant decision to discontinue treatment.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 of every 28-day cycle. Day 15: Atezolizumab may be administered on Days 15-18 of each cycle.

Nab-Paclitaxel

Intervention Type: DRUG

Nab-Paclitaxel will be administered at the 100 mg/m2 dose via IV infusion on Days 1, 8, and 15 of every 28-day cycle. Day 8: Nab-paclitaxel may be administered on Days 8-11 of each cycle. Day 15: Nab-paclitaxel may be administered on Days 15-18 of each cycle, on the same day with the atezolizumab infusion.

Interventions

Atezolizumab

Atezolizumab will be administered at a dose of 840 mg via IV infusion on Days 1 and 15 of every 28-day cycle. Day 15: Atezolizumab may be administered on Days 15-18 of each cycle.

Intervention Type: DRUG

Nab-Paclitaxel

Nab-Paclitaxel will be administered at the 100 mg/m2 dose via IV infusion on Days 1, 8, and 15 of every 28-day cycle. Day 8: Nab-paclitaxel may be administered on Days 8-11 of each cycle. Day 15: Nab-paclitaxel may be administered on Days 15-18 of each cycle, on the same day with the atezolizumab infusion.

Intervention Type: DRUG

Other Intervention Names

Tecentriq; Abraxane

Eligibility Criteria

Inclusion Criteria

• Unresectable locally advanced or metastatic, histologically documented TNBC (negative for HER2 and ER and PgR)
• At least one specimen positive for PD-L1 status as determined by VENTANA PD-L1 SP142 IHC Assay
• No prior chemotherapy, experimental or targeted systemic therapy for unresectable locally advanced or metastatic TNBC
• Eastern Cooperative Oncology Group (ECOG) performance status of 0, 1 or 2
• Life expectancy ≥ 12 weeks
• Measurable disease, as defined by RECIST v1.1
• Adequate haematologic and end-organ function, defined by the following laboratory results obtained within 14 days prior to the initiation of study treatment
• Negative hepatitis B surface antigen (HBsAg) test at screening
• Negative total hepatitis B core antibody (HBcAb) test at screening, or positive HBcAb test followed by a negative hepatitis B virus (HBV) deoxyribonucleic acid (DNA) test at screening
• Negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening
• Patients with treated asymptomatic central nervous system (CNS) metastases are eligible, provided that all the following criteria are met: (a) The metastases are limited to the supratentorial region or cerebellum (b) No ongoing requirement for corticosteroids as therapy for CNS disease (c) No stereotactic radiation within 7 days or whole-brain radiation or neurosurgical resection within 2 weeks before the start of study treatment (d) Radiographic demonstration of interim stability between the completion of CNS-directed therapy and the screening imaging study.
• Patients with a history of autoimmune disease (Appendix 2) are allowed if controlled and on stable treatment (i.e., same treatment, same dose) for the last 12 weeks
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods that result in a failure rate of < 1% per year, during the treatment period and for at least 5 months after the last dose of atezolizumab or 6 months after the last dose of nab-paclitaxel/paclitaxel, whichever is later. In addition, women must refrain from donating eggs during the same time period
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm
• Women who are not postmenopausal (≥ 12 months of non-therapy-induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug

Exclusion Criteria

• 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 > 2 weeks prior to the first dose of study treatment (Cycle 1, Day 1).
• Leptomeningeal carcinomatosis or any symptomatic CNS metastases
• Uncontrolled symptomatic pleural effusion, pericardial effusion, or ascites
• Uncontrolled tumour-related pain
• Uncontrolled hypercalcemia (> 1.5 mmol/L ionized calcium or calcium > 12 mg/dL or corrected serum calcium > ULN) or symptomatic hypercalcemia requiring continued use of bisphosphonate therapy.
• Malignancies other than breast cancer within 5 years prior to the first dose of study treatment (Cycle 1, Day 1), with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome

• Pregnancy or lactation
• Evidence of significant uncontrolled concomitant disease that could affect compliance with the protocol or interpretation of results, including significant liver disease
• Significant cardiovascular disease such as New York Heart Association (NYHA) cardiac disease (Class II or greater), myocardial infarction within 3 months prior to the first dose of study treatment (Cycle 1, Day 1), unstable arrhythmias, or unstable angina
• Severe infection within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), including but not limited to hospitalization for complications of infection, bacteraemia, or severe pneumonia, or any active infection, that in the opinion of the investigator, could impact patient safety.
• Treatment with oral or IV antibiotics within 2 weeks prior to initiation of study treatment (Cycle 1, Day 1)
• Major surgical procedure within 28 days prior to the first dose of study treatment (Cycle 1, Day 1), or anticipation of the need for a major surgical procedure during the course of the study (other than diagnostic procedures)
• Treatment with investigational therapy within 4 weeks prior to Cycle 1, Day 1
• Known hypersensitivity to nab-paclitaxel or any of the excipients, when nab-paclitaxel is used as a backbone taxane
• Known hypersensitivity to paclitaxel or any of the excipients, when paclitaxel is used as a backbone taxane
• Positive human immunodeficiency virus (HIV) test at screening, unless the patient meets all of the following conditions: stable on anti-retroviral therapy, CD4 count ≥200/mL, undetectable viral load
• Any other disease, metabolic dysfunction, physical examination finding, or clinical laboratory finding that contraindicates the use of an investigational drug, may affect the interpretation of the results, or may render the patient at high risk from treatment complications

• History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation
• Prior allogenic stem cell or solid organ transplantation
• History of idiopathic pulmonary fibrosis (including pneumonitis), drug-induced pneumonitis, organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia), or evidence of active pneumonitis on screening chest CT scan
• Current treatment with anti-viral therapy for HBV
• Active tuberculosis
• Receipt of a live, attenuated vaccine within 4 weeks prior to the first dose of study treatment (Cycle 1, Day 1), or anticipation that such a live, attenuated vaccine will be required during atezolizumab treatment or within 5 months following the final dose of atezolizumab
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies (including anti-CTLA4 antibodies), except for anti-PD-1 or anti-PD-L1 antibodies.
• Treatment with systemic immunostimulatory agents (including but not limited to interferons or IL-2) within 4 weeks or five half-lives of the drug (whichever is longer) prior to the first dose of study treatment (Cycle 1, Day 1)
• Only in patients without autoimmune disease: Treatment with systemic corticosteroids or other systemic immunosuppressive medications (including but not limited to prednisone, dexamethasone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and antitumour necrosis factor [TNF] agents) within 2 weeks prior to the first dose of study treatment (Cycle 1, Day 1), or anticipated requirement for systemic immunosuppressive medications during the study

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

CEMIC

Buenos Aires, , Argentina

Sanatorio de la Mujer

Rosario, , Argentina

Organizacion Medica de Investigacion

San Nicolás, , Argentina

Instituto de Radiomedicina, IRAM

Santiago, , Chile

Pontificia Universidad Catolica de Chile

Santiago, , Chile

Nemocnice AGEL Novy Jicin a.s.

Nový Jičín, , Czechia

Fakultni Poliklinika Vseobecne Fakultni Niemocnice

Prague, , Czechia

Nemocnice na Bulovce

Prague, , Czechia

Institut de Cancérologie de Bourgogne

Dijon, , France

Hôpital Franco-Britannique- Fondation Cognacq-Jay

Levallois-Perret, , France

Centre Leon Berard

Lyon, , France

Institut de cancerologie du Gard

Nîmes, , France

Clinique Onco Des Dentellieres

Valenciennes, , France

Departement Medecine

Villejuif, , France

Debreceni Egyetem Klinikai Kozpont

Debrecen, , Hungary

Bács-Kiskun Vármegyei Oktatókórház

Kecskemét, , Hungary

B-A-Z Vármegyei Központi Kórház és Egyetemi Oktatókórház

Miskolc, , Hungary

Komarom-Eszergom Varmegyei Szent Borbala Korhaz

Tatabánya, , Hungary

Zala Vármegyei Szent Rafael Kórház

Zalaegerszeg, , Hungary

Azienda Universitaria Magna Grecia

Catanzaro, Calabria, Italy

Azienda Ospedaliera San Giuseppe Moscati

Avellino, Campania, Italy

Policlinico Universitario Agostino Gemelli

Rome, Lazio, Italy

Irccs Ospedale San Raffaele

Milan, Lombardy, Italy

Istituto Europeo Di Oncologia

Milan, Lombardy, Italy

Ospedale San Gerardo

Monza, Lombardy, Italy

Fondazione IRCCS Policlinico San Matteo, Oncologia

Pavia, Lombardy, Italy

Ospedale Civile

Sassari, Sardinia, Italy

Ospedale Cannizzaro, Oncologia

Catania, Sicily, Italy

Fondazione del Piemonte per l?Oncologia (IRCCS)

Candiolo, Trentino-Alto Adige, Italy

Ospedale Santa Chiara

Trento, Trentino-Alto Adige, Italy

Azienda ospedaliero-universitaria careggi, Sezione di radioterapia del dipartimento di fisiopatolo

Florence, Tuscany, Italy

Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico

Pisa, Tuscany, Italy

Nuovo Ospedale di Prato S. Stefano - Azienda USL Toscana Centro

Prato, Tuscany, Italy

Clinica Oncologica-Ospedali Riuniti Ancona

Torrette, Tuscany, Italy

USL Umbria 1 - Osp. Città di Castello

Città Di Castello (PG), Umbria, Italy

AULSS3 - Presidio di Mirano

Mirano (VE), Veneto, Italy

Hospital de Oncología Siglo XXI

Mexico City, Mexico CITY (federal District), Mexico

Instituto Nacional de Cancerologia

Distrito Federal, , Mexico

Instituto Nacional de Enfermedades Neoplasicas

Lima, , Peru

Hospital Nacional Cayetano Heredia

Lima, , Peru

Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny

Brzozów, , Poland

Szpital Wojewódzki im. Miko?aja Kopernika

Koszalin, , Poland

Ars Medical Sp. z o. o.

Pi?a, , Poland

MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie

Rzeszów, , Poland

Hospital Garcia de Orta

Almada, , Portugal

IPO de Coimbra

Coimbra, , Portugal

IPO de Lisboa

Lisbon, , Portugal

Hospital de S. Francisco Xavier

Lisbon, , Portugal

Hospital Cuf Descobertas

Lisbon, , Portugal

IPO do Porto

Porto, , Portugal

Prof. Dr. I. Chiricuta Institute of Oncology

Cluj-Napoca, , Romania

Centrul de Oncologie Sfantul Nectarie

Craiova, , Romania

Centrul de Radioterapie AMETHYST

Floreşti, , Romania

Institute of Oncology Ljubljana

Ljubljana, , Slovenia

Univerzitetni klini?ni center Maribor

Maribor, , Slovenia

Hospital General Universitario de Elche

Elche, Alicante, Spain

Corporacio Sanitaria Parc Tauli

Sabadell, Barcelona, Spain

Hospital Alvaro Cunqueiro

Vigo, Pontevedra, Spain

Hospital Univ. Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital de Basurto

Bilbao, Vizcaya, Spain

Hospital Universitario San Cecilio

Granada, , Spain

Hospital Universitari Arnau de Vilanova de Lleida

Lleida, , Spain

Hospital Lucus Augusti

Lugo, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Clinico Universitario Virgen de la Victoria

Málaga, , Spain

Hospital General Universitario J.M Morales Meseguer

Murcia, , Spain

Hospital Clinico Universitario de Salamanca

Salamanca, , Spain

Countries

China; Slovakia; Argentina; Chile; Czechia; France; Hungary; Italy; Mexico; Peru; Poland; Portugal; Romania; Slovenia; Spain

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

2019-002488-91

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MO39874

Identifier Type: -

Identifier Source: org_study_id