Clinical Trials /

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

NCT04148911

Description:

Study MO39874 is an open-label, phase IIIb, single arm, multicenter study to evaluate the safety and treatment efficacy of atezolizumab plus nab-paclitaxel/paclitaxel in patients with PD-L1-positive unresectable locally advanced or metastatic triple-negative adenocarcinoma of the breast (TNBC) who have not received prior systemic cytotoxic therapy for unresectable locally advanced or metastatic TNBC.

Related Conditions:
  • Breast Adenocarcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Study of Atezolizumab (Tecentriq) Plus Nab-Paclitaxel or Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer
  • Official Title: An Open-Label, Phase IIIIb, Single Arm, Multicenter Safety Study of Atezolizumab (Tecentriq) Plus Nab-Paclitaxel or Paclitaxel in the Treatment of Unresectable Locally Advanced or Metastatic Triple-Negative Breast Cancer

Clinical Trial IDs

  • ORG STUDY ID: MO39874
  • SECONDARY ID: 2019-002488-91
  • NCT ID: NCT04148911

Conditions

  • Triple-Negative Breast Cancer

Interventions

DrugSynonymsArms
AtezolizumabTecentriqAtezolizumab plus Nab-Paclitaxel or Paclitaxel
Nab-PaclitaxelAbraxaneAtezolizumab plus Nab-Paclitaxel or Paclitaxel
PaclitaxelTaxol, OnxalAtezolizumab plus Nab-Paclitaxel or Paclitaxel

Purpose

Study MO39874 is an open-label, phase IIIb, single arm, global study to evaluate the safety and treatment efficacy of atezolizumab plus nabpaclitaxel/paclitaxel in patients with PD-L1-positive unresectable locally advanced or metastatic triple-negative adenocarcinoma of the breast (TNBC) who have not received prior systemic cytotoxic therapy for unresectable locally advanced or metastatic TNBC.

Trial Arms

NameTypeDescriptionInterventions
Atezolizumab plus Nab-Paclitaxel or PaclitaxelExperimentalParticipants will receive Atezolizumab via intravenous (IV) infusion on Days 1, 8 and 15 of every 28-day cycle in combination with Nab-Paclitaxel or Paclitaxel (individually selected by the investigator)
  • Atezolizumab
  • Nab-Paclitaxel
  • Paclitaxel

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
             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 asymptomatic central nervous system (CNS) metastases are eligible

          -  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 TNBC 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

          -  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 the study

          -  Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including
             anti-CTLA4 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Percentage of Participants with treatment-emergent Grade≥3 AEs
Time Frame:From baseline to up to 3 years
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Percentage of Participants with all treatment-emergent AEs
Time Frame:From baseline to up to 3 years
Safety Issue:
Description:
Measure:Percentage of Participants with treatment-emergent SAEs
Time Frame:From baseline to up to 3 years
Safety Issue:
Description:
Measure:Overall survival (OS)
Time Frame:From baseline to 3 years
Safety Issue:
Description:OS defined as the time from initiation of study treatment to death from any cause.
Measure:Progression Free Survival (PFS)
Time Frame:From baseline to 3 years
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Hoffmann-La Roche

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