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

Triple-Negative Breast Cancer Clinical Trial

— EL1SSAR  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04148911
• Other study ID #: MO39874
• Secondary ID: 2019-002488-91
• Status: Active, not recruiting
• Phase: Phase 3
• Start date: December 17, 2019
• Est. completion date: December 15, 2024

Study information

• Verified date: June 2024
• Source: Hoffmann-La Roche
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 184
• Est. completion date: December 15, 2024
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Breast Neoplasms
• Triple Negative Breast Neoplasms
• Triple-Negative Breast Cancer

Intervention

Drug:
• 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.
• 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.

Locations

Country	Name	City	State
Argentina	Cemic; Oncologia Clinica	Buenos Aires
Argentina	Sanatorio de la Mujer	Rosario
Argentina	Organizacion Medica de Investigacion	San Nicolás
Chile	Instituto de Radiomedicina, IRAM	Santiago
Chile	Pontificia Universidad Catolica de Chile; Centro Del Cáncer	Santiago
Czechia	Fakultni nemocnice Brno; Interni hematologicka a onkologicka klinika	Brno
Czechia	Nemocnice AGEL Novy Jicin a.s.; Oddeleni radioterapie a onkologie	Novy Jicin
Czechia	Fakultni Poliklinika Vseobecne Fakultni Niemocnice; Onkologicka Klinika	Praha 2
Czechia	Fakultni nemocnice v Motole; Onkologicka klinika 2. LF UK a FN Motol	Praha 5
Czechia	Nemocnice na Bulovce; Ustav radiacni onkologie	Praha 8
France	Hopital Avicenne; Cancerologie	Bobigny
France	Institut de Cancérologie de Bourgogne; Oncologie Médicale	Dijon
France	Hôpital Franco-Britannique- Fondation Cognacq-Jay; Cancerologie	Levallois-Perret
France	CENTRE LEON BERARD; Département d?Hématologie et d?Oncologie	Lyon
France	Institut de cancerologie du Gard	Nimes
France	Chp Saint Gregoire; Cancerologie Radiotherapie	Saint Gregoire
France	Clinique Onco Des Dentellieres; Chimiotherapie Radiotherapie	Valenciennes
France	Departement Medecine; Immunotherapie	Villejuif
Hungary	Debreceni Egyetem Klinikai Kozpont ; Department of Oncology	Debrecen
Hungary	Bács-Kiskun Vármegyei Oktatókórház; Onkoradiológiai Központ	Kecskemét
Hungary	B-A-Z Vármegyei Központi Kórház és Egyetemi Oktatókórház; Klin. Onkológiai és Sugárterápiás Centrum	Miskolc
Hungary	Komarom-Eszergom Varmegyei Szent Borbala Korhaz; Onkologiai Osztaly	Tatabanya
Hungary	Zala Vármegyei Szent Rafael Kórház; Onkológiai Osztály	Zalaegerszeg
Italy	Azienda Ospedaliera San Giuseppe Moscati	Avellino	Campania
Italy	Presidio Ospedaliero di Summa-Perrino; Oncologia Medica	Brindisi	Puglia
Italy	Fondazione del Piemonte per l?Oncologia (IRCCS)	Candiolo	Piemonte
Italy	Ospedale Cannizzaro, Oncologia	Catania	Sicilia
Italy	Azienda Universitaria Magna Grecia; Dip. di Medicina Sperimentale e Clinica_U.O. Oncologia Medica	Catanzaro	Calabria
Italy	USL Umbria 1 - Osp. Città di Castello; U.O. di Oncologia	Città Di Castello (PG)	Umbria
Italy	Azienda ospedaliero-universitaria careggi, Sezione di radioterapia del dipartimento di fisiopatolo	Firenze	Toscana
Italy	Ospedale Della Misericordia; U.O. Di Medicina Ia - Oncologia Medica	Grosseto	Toscana
Italy	Ospedale Di Macerata; Oncologia	Macerata	Marche
Italy	Irccs Ospedale San Raffaele	Milano	Lombardia
Italy	Istituto Europeo Di Oncologia	Milano	Lombardia
Italy	AULSS3 - Presidio di Mirano; Dip. di Oncologia	Mirano (VE)	Veneto
Italy	Ospedale San Gerardo	Monza	Lombardia
Italy	Fondazione IRCCS Policlinico San Matteo, Oncologia	Pavia	Lombardia
Italy	Azienda Ospedaliero - Universitaria Pisana U.O. Oncologia Medica 2 Universitaria ? Polo Oncologico	Pisa	Toscana
Italy	Nuovo Ospedale di Prato S. Stefano - Azienda USL Toscana Centro	Prato	Toscana
Italy	Policlinico Universitario Agostino Gemelli	Roma	Lazio
Italy	Ospedale Civile; Oncologia Medica	Sassari	Sardegna
Italy	Clinica Oncologica-Ospedali Riuniti Ancona	Torrette	Toscana
Italy	Ospedale Santa Chiara; Oncologia Medica	Trento	Trentino-Alto Adige
Mexico	Hospital de Oncología Siglo XXI	Ciudad de México	Mexico CITY (federal District)
Mexico	Instituto Nacional de Cancerologia; Oncology	Mexico City
Peru	Hospital Central Fap Juan Benavides Dorich; Oncology	Lima
Peru	Hospital Nacional Cayetano Heredia; Hematology - Oncology	Lima
Peru	Instituto Nacional de Enfermedades Neoplasicas	Lima
Poland	Szpital Specjalistyczny Podkarpacki O?rodek Onkologiczny	Brzozów
Poland	Przychodnia Lekarska KOMED, Roman Karaszewski	Konin
Poland	Szpital Wojewódzki im. Miko?aja Kopernika; Oddzia? Dzienny Chemioterapii	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	Rzeszow
Portugal	Hospital Garcia de Orta; Servico de Oncologia Medica	Almada
Portugal	IPO de Coimbra; Servico de Oncologia Medica	Coimbra
Portugal	Hospital Cuf Descobertas; Unidade de Oncologia	Lisboa
Portugal	Hospital de S. Francisco Xavier; Unidade de Oncologia Medica	Lisboa
Portugal	IPO de Lisboa; Servico de Oncologia Medica	Lisboa
Portugal	IPO do Porto; Servico de Oncologia Medica	Porto
Romania	Prof. Dr. I. Chiricuta Institute of Oncology	Cluj Napoca
Romania	Centrul de Oncologie Sfantul Nectarie	Craiova
Romania	Centrul de Radioterapie AMETHYST	Floresti
Slovenia	Institute of Oncology Ljubljana	Ljubljana
Slovenia	Univerzitetni klini?ni center Maribor; Oddelek za onkologijo	Maribor
Spain	Hospital de Basurto; Servicio de Oncologia	Bilbao	Vizcaya
Spain	Hospital General Universitario de Elche; Servicio de Oncologia	Elche	Alicante
Spain	Hospital Universitario San Cecilio; Servicio de Oncologia	Granada
Spain	Hospital Universitari Arnau de Vilanova de Lleida; Servicio de Oncologia	Lerida
Spain	Hospital Lucus Augusti; Servicio de Oncologia	Lugo
Spain	Hospital Universitario 12 de Octubre; Servicio de Oncologia	Madrid
Spain	Hospital Clinico Universitario Virgen de la Victoria; Servicio de Oncologia	Malaga
Spain	Hospital General Universitario J.M Morales Meseguer; Servicio de Oncologia	Murcia
Spain	Hospital Univ. Central de Asturias; Servicio de Oncologia	Oviedo	Asturias
Spain	Corporacio Sanitaria Parc Tauli; Servicio de Oncologia	Sabadell	Barcelona
Spain	Hospital Clinico Universitario de Salamanca; Servicio de Oncologia	Salamanca
Spain	Hospital Alvaro Cunqueiro	Vigo	Pontevedra

Sponsors (1)

Lead Sponsor	Collaborator
Hoffmann-La Roche

Countries where clinical trial is conducted

Argentina,  Chile,  Czechia,  France,  Hungary,  Italy,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Slovenia,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants with treatment-emergent Grade=3 AEs		From baseline to up to 4.5 years
Primary	Percentage of Participants with treatment-emergent Grade=2 imAEs		From baseline to up to 4.5 years
Secondary	Percentage of Participants with all treatment-emergent AEs		From baseline to up to 4.5 years
Secondary	Percentage of Participants with treatment-emergent SAEs		From baseline to up to 4.5 years
Secondary	Overall survival (OS) in ITT Population	OS defined as the time from initiation of study treatment to death from any cause.	From baseline to 4.5 years
Secondary	Overall survival (OS) in PD-L1-Positive Tumor Status Population	OS defined as the time from initiation of study treatment to death from any cause.	From baseline to 4.5 years
Secondary	Progression Free Survival (PFS) in ITT Population	PFS defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator according to RECIST v1.1.	From baseline to 4.5 years
Secondary	Progression Free Survival (PFS) in PD-L1-Positive Tumor Status Population	PFS defined as the time from initiation of study treatment to the first occurrence of disease progression or death from any cause, whichever occurs first. PFS will be assessed by the investigator according to RECIST v1.1.	From baseline to 4.5 years