Clinical trial NCT04148911: A Study of Atezolizumab Plus Nab-Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic PD-L1-Positive Triple-Negative Breast Cancer
Official title: An Open-Label, Phase IIIb, Single Arm, Multicenter Safety Study of Atezolizumab (Tecentriq) Plus Nab-Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Triple-Negative Breast Cancer
Lead sponsor: Hoffmann-La Roche
Sponsor class: INDUSTRY
First posted: 2019-11-04
Enrollment: 184
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is an open-label (non-blinded), single arm safety study in which all participants will receive atezolizumab in combination with nab-paclitaxel.
Primary purpose: TREATMENT

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.


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:

Cancer- Specific 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

General Medical Exclusion Criteria:

* 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

Exclusion Criteria Related to Atezolizumab:

* 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

Primary outcomes:
measure: Percentage of Participants with treatment-emergent Grade≥3 AEs
timeFrame: From baseline to up to 4.5 years
measure: Percentage of Participants with treatment-emergent Grade≥2 imAEs
timeFrame: From baseline to up to 4.5 years
Secondary outcomes:
measure: Percentage of Participants with all treatment-emergent AEs
timeFrame: From baseline to up to 4.5 years
measure: Percentage of Participants with treatment-emergent SAEs
timeFrame: From baseline to up to 4.5 years
measure: Overall survival (OS) in ITT Population
timeFrame: From baseline to 4.5 years
measure: Overall survival (OS) in PD-L1-Positive Tumor Status Population
timeFrame: From baseline to 4.5 years
measure: Progression Free Survival (PFS) in ITT Population
timeFrame: From baseline to 4.5 years
measure: Progression Free Survival (PFS) in PD-L1-Positive Tumor Status Population
timeFrame: From baseline to 4.5 years
Other outcomes:
Locations:
city: Buenos Aires
country: Argentina
facility: CEMIC
city: Rosario
country: Argentina
facility: Sanatorio de la Mujer
city: San Nicolás
country: Argentina
facility: Organizacion Medica de Investigacion
city: Santiago
country: Chile
facility: Instituto de Radiomedicina, IRAM
city: Santiago
country: Chile
facility: Pontificia Universidad Catolica de Chile
city: Novy Jicin
country: Czechia
facility: Nemocnice AGEL Novy Jicin a.s.
city: Praha 2
country: Czechia
facility: Fakultni Poliklinika Vseobecne Fakultni Niemocnice
city: Praha 8
country: Czechia
facility: Nemocnice na Bulovce
city: Dijon
country: France
facility: Institut de Cancérologie de Bourgogne
city: Levallois-Perret
country: France
facility: Hôpital Franco-Britannique- Fondation Cognacq-Jay
city: Lyon
country: France
facility: Centre Leon Berard
city: Nimes
country: France
facility: Institut de cancerologie du Gard
city: Valenciennes
country: France
facility: Clinique Onco Des Dentellieres
city: Villejuif
country: France
facility: Departement Medecine
city: Debrecen
country: Hungary
facility: Debreceni Egyetem Klinikai Kozpont
city: Kecskemét
country: Hungary
facility: Bács-Kiskun Vármegyei Oktatókórház
city: Miskolc
country: Hungary
facility: B-A-Z Vármegyei Központi Kórház és Egyetemi Oktatókórház
city: Tatabánya
country: Hungary
facility: Komarom-Eszergom Varmegyei Szent Borbala Korhaz
city: Zalaegerszeg
country: Hungary
facility: Zala Vármegyei Szent Rafael Kórház
city: Catanzaro
country: Italy
facility: Azienda Universitaria Magna Grecia
state: Calabria
city: Avellino
country: Italy
facility: Azienda Ospedaliera San Giuseppe Moscati
state: Campania
city: Roma
country: Italy
facility: Policlinico Universitario Agostino Gemelli
state: Lazio
city: Milano
country: Italy
facility: Irccs Ospedale San Raffaele
state: Lombardia
city: Milano
country: Italy
facility: Istituto Europeo Di Oncologia
state: Lombardia
city: Monza
country: Italy
facility: Ospedale San Gerardo
state: Lombardia
city: Pavia
country: Italy
facility: Fondazione IRCCS Policlinico San Matteo, Oncologia
state: Lombardia
city: Sassari
country: Italy
facility: Ospedale Civile
state: Sardegna
city: Catania
country: Italy
facility: Ospedale Cannizzaro, Oncologia
state: Sicilia
city: Firenze
country: Italy
facility: Azienda ospedaliero-universitaria careggi, Sezione di radioterapia del dipartimento di fisiopatolo
state: Toscana
city: Pisa
country: Italy
facility: Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico
state: Toscana
city: Prato
country: Italy
facility: Nuovo Ospedale di Prato S. Stefano - Azienda USL Toscana Centro
state: Toscana
city: Torrette
country: Italy
facility: Clinica Oncologica-Ospedali Riuniti Ancona
state: Toscana
city: Candiolo
country: Italy
facility: Fondazione del Piemonte per l?Oncologia (IRCCS)
state: Trentino-Alto Adige
city: Trento
country: Italy
facility: Ospedale Santa Chiara
state: Trentino-Alto Adige
city: Città Di Castello (PG)
country: Italy
facility: USL Umbria 1 - Osp. Città di Castello
state: Umbria
city: Mirano (VE)
country: Italy
facility: AULSS3 - Presidio di Mirano
state: Veneto
city: Ciudad de México
country: Mexico
facility: Hospital de Oncología Siglo XXI
state: Mexico CITY (federal District)
city: Distrito Federal
country: Mexico
facility: Instituto Nacional de Cancerologia
city: Lima
country: Peru
facility: Instituto Nacional de Enfermedades Neoplasicas
city: Lima
country: Peru
facility: Hospital Nacional Cayetano Heredia
city: Brzozów
country: Poland
facility: Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny
city: Koszalin
country: Poland
facility: Szpital Wojewódzki im. Miko?aja Kopernika
city: Pi?a
country: Poland
facility: Ars Medical Sp. z o. o.
city: Rzeszow
country: Poland
facility: MRUKMED Lekarz Beata Madej-Mruk i Partner Spolka Partnerska Oddzial nr 1 w Rzeszowie
city: Almada
country: Portugal
facility: Hospital Garcia de Orta
city: Coimbra
country: Portugal
facility: IPO de Coimbra
city: Lisboa
country: Portugal
facility: IPO de Lisboa
city: Lisboa
country: Portugal
facility: Hospital de S. Francisco Xavier
city: Lisboa
country: Portugal
facility: Hospital Cuf Descobertas
city: Porto
country: Portugal
facility: IPO do Porto
city: Cluj Napoca
country: Romania
facility: Prof. Dr. I. Chiricuta Institute of Oncology
city: Craiova
country: Romania
facility: Centrul de Oncologie Sfantul Nectarie
city: Floresti
country: Romania
facility: Centrul de Radioterapie AMETHYST
city: Ljubljana
country: Slovenia
facility: Institute of Oncology Ljubljana
city: Maribor
country: Slovenia
facility: Univerzitetni klini?ni center Maribor
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Oviedo
country: Spain
facility: Hospital Univ. Central de Asturias
state: Asturias
city: Sabadell
country: Spain
facility: Corporacio Sanitaria Parc Tauli
state: Barcelona
city: Vigo
country: Spain
facility: Hospital Alvaro Cunqueiro
state: Pontevedra
city: Bilbao
country: Spain
facility: Hospital de Basurto
state: Vizcaya
city: Granada
country: Spain
facility: Hospital Universitario San Cecilio
city: Lerida
country: Spain
facility: Hospital Universitari Arnau de Vilanova de Lleida
city: Lugo
country: Spain
facility: Hospital Lucus Augusti
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Malaga
country: Spain
facility: Hospital Clinico Universitario Virgen de la Victoria
city: Murcia
country: Spain
facility: Hospital General Universitario J.M Morales Meseguer
city: Salamanca
country: Spain
facility: Hospital Clinico Universitario de Salamanca
Study officials:
affiliation: Hoffmann-La Roche
name: Clinical Trials
role: STUDY_DIRECTOR
References: