Breast Cancer Clinical Trial

A Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatment Combinations in Patients With Metastatic or Inoperable Locally Advanced Triple-Negative Breast Cancer

Summary

This is a Phase Ib/II, open-label, multicenter, randomized umbrella study evaluating the efficacy and safety of multiple immunotherapy-based treatment combinations in patients with metastatic or inoperable locally advanced TNBC.

The study will be performed in two stages. During Stage 1, two cohorts will be enrolled in parallel in this study: one cohort will consist of Programmed death-ligand 1 (PD-L1)-positive participants who have received no prior systemic therapy for metastatic or inoperable locally advanced triple-negative breast cancer (TNBC) (first-line [1L] PD-L1+ cohort), and one cohort will consist of participants who had disease progression during or following 1L treatment with chemotherapy (e.g., paclitaxel, nab-paclitaxel, carboplatin) and have not received cancer immunotherapy (CIT) (second-line [2L] CIT-naive cohort). In addition, participants in the 2L CIT-naive cohort who experience disease progression, loss of clinical benefit, or unacceptable toxicity during Stage 1 may be eligible to continue treatment with a different treatment combination (Stage 2), provided Stage 2 is open for enrollment.

View Eligibility Criteria

Eligibility Criteria

Inclusion Criteria Stage 1

Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
Metastatic or inoperable locally advanced, histologically documented TNBC (absence of HER2, ER, and PR expression)
For the 1L PD L1+ cohort: no prior systemic treatment for metastatic or inoperable locally advanced TNBC
For the 2L CIT-naive cohort: Eligible for capecitabine monotherapy
For the 2L CIT-naive cohort: Radiologic/objective evidence of recurrence or disease progression after 1L treatment with chemotherapy, for a total of one line of therapy for inoperable locally advanced or metastatic breast cancer
Life expectancy =/> 3 months, as determined by the investigator
Tumor accessible for biopsy
Availability of a representative tumor specimen that is suitable for determination of PD-L1 and/or additional biomarker status via central testing
For the 1L PD L1+ cohort: Positive PD-L1 expression, defined as >/= 1% of the tumor area occupied by PD L1-expressing tumor-infiltrating immune cells of any intensity, as determined through use of the U.S. Food and Drug Administration-approved or CE-marked Ventana PD-L1 (SP142) Assay

Inclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naive cohort)

Measurable disease (at least one target lesion)
Adequate hematologic and end-organ function, laboratory test results, obtained within 14 days prior to initiation of study treatment.
Negative HIV test at screening
Negative hepatitis B surface antigen test
Negative total hepatitis B core antibody (HBcAb)
Negative hepatitis C virus (HCV) antibody test at screening
For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from breastfeeding and donating eggs as outlined for each specific treatment arm
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures, and agreement to refrain from donating sperm, as outlined for each specific treatment arm

Inclusion Criteria Stage 2 (2L CIT-naive cohort)

ECOG Performance Status of 0, 1, or 2
Patients randomly allocated to the control arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity, provided that Medical Monitor approval for entry into Stage 2 is obtained, or disease progression per RECIST v1.1 while receiving control treatment
Patients randomly allocated to an experimental arm during Stage 1: ability to initiate Stage 2 treatment within 3 months after experiencing unacceptable toxicity not related to atezolizumab, disease progression per RECIST v1.1, or loss of clinical benefit as determined by the investigator while receiving Stage 1 treatment
Availability of a tumor specimen from a biopsy performed upon discontinuation of Stage 1 (if deemed clinically feasible by the investigator)

Exclusion Criteria for Stage 1

Prior treatment with T-cell co-stimulating or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies, CD40 agonists or interleukin-2 (IL-2) or IL-2-like compounds
Treatment with investigational therapy within 28 days prior to initiation of study treatment
Biologic treatment (e.g., bevacizumab) within 2 weeks prior to initiation of study treatment, or other systemic treatment for TNBC within 2 weeks or 5 half-lives of the drug (whichever is longer) prior to initiation of study treatment
Adverse events from prior anti-cancer therapy that have not resolved to Grade Eligibility only for the control arm

Exclusion Criteria for Stage 1 (both cohorts) and Stage 2 (2L CIT-naïve cohort)

Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently)
Uncontrolled tumor-related pain
Symptomatic, untreated, or actively progressing central nervous system (CNS) metastases
History of leptomeningeal disease
Active or history of autoimmune disease or immune deficiency
History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan. History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
Active tuberculosis
Severe infection within 4 weeks prior to initiation of study treatment
Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiation of study treatment
Significant cardiovascular disease
Prior allogeneic stem cell or solid organ transplantation
History of malignancy other than breast cancer within 2 years prior to screening, with the exception of those with a negligible risk of metastasis or death
Treatment with systemic immunosuppressive medication (including, but not limited to, corticosteroids, cyclophosphamide, azathioprine, methotrexate, thalidomide, and anti-tumor necrosis factor alpha agents) within 2 weeks prior to initiation of study treatment, or anticipation of need for systemic immunosuppressive medication during the course of the study
Pregnancy or breastfeeding, or intention of becoming pregnant during the study

Exclusion Criteria for the 2L CIT-naive cohort, Stage 1

Prior treatment with capecitabine,
Treatment with sorivudine or its chemically related analogues, such as brivudine
History of severe and unexpected reactions to fluoropyrimidine therapy
Known complete absence of dihydropyrimidine dehydrogenase activity

Exclusion Criteria for Stage 2

Inability to tolerate atezolizumab during Stage 1
For patients receiving eribulin: congenital long QT syndrome

Additional drug-specific exclusion criteria may apply to Stage 1 and 2

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

280

Study ID:

NCT03424005

Recruitment Status:

Recruiting

Sponsor:

Hoffmann-La Roche

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There are 36 Locations for this study

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City of Hope
Duarte California, 91010, United States
University of California San Diego Medical Center; Moores Cancer Center
La Jolla California, 92093, United States
Stanford Cancer Institute
Stanford California, 94305, United States
Rocky Mountain Cancer Center - Longmont
Longmont Colorado, 80504, United States
H. Lee Moffitt Cancer Center and Research Inst.
Tampa Florida, 33612, United States
Hackensack Univ Medical Center; John Theurer Cancer Ctr
Hackensack New Jersey, 07601, United States
Regional Cancer Care Associates, LLC
Howell New Jersey, 07731, United States
Rutgers Cancer Institute of New Jersey
New Brunswick New Jersey, 08901, United States
NYU Langone Medical Center; NYU Perlmutter Cancer Center
New York New York, 10016, United States
Thomas Jefferson University Hospital
Philadelphia Pennsylvania, 19107, United States
University of Pittsburgh Medical Center
Pittsburgh Pennsylvania, 15213, United States
The West Clinic; West Cancer Center
Germantown Tennessee, 38138, United States
Vanderbilt University Medical Center; Vanderbilt University
Nashville Tennessee, 37232, United States
Texas Oncology-Plano East
Plano Texas, 75075, United States
Peter MacCallum Cancer Centre-East Melbourne
Melbourne Victoria, 3000, Australia
Fiona Stanley Hospital - Medical Oncology
Murdoch Western Australia, 6150, Australia
Centre Léon Bérard
Lyon , 69008, France
Institut régional du Cancer Montpellier
Montpellier , 34298, France
Institut Universitaire du Cancer de Toulouse-Oncopole
Toulouse , 31059, France
Gustave Roussy
Villejuif CEDEX , 94800, France
Universitätsklinikum Erlangen; Frauenklinik
Erlangen , 91054, Germany
Universitätsklinikum Essen
Essen , 45147, Germany
Shaare Zedek Medical Center
Jerusalem , 91031, Israel
Hadassah University Medical Center
Jerusalem , , Israel
Rabin MC; Davidof Center - Oncology Institute
Petach Tikva , 49414, Israel
Sheba Medical Center
Ramat Gan , 52621, Israel
Tel-Aviv Sourasky Medical Center
Tel Aviv , 64239, Israel
Seoul National University Hospital
Seoul , 03080, Korea, Republic of
Severance Hospital
Seoul , 03722, Korea, Republic of
University of Ulsan College of Medicine - Asan Medical Center
Seoul , 05505, Korea, Republic of
Hospital del Mar
Barcelona , 08003, Spain
Vall d´Hebron Institute of Oncology (VHIO), Barcelona
Barcelona , 08035, Spain
Hospital Universitario Ramon y Cajal
Madrid , 28034, Spain
Centro Integral Oncológico Clara Campal Ensayos Clínicos START
Madrid , 28050, Spain
Hospital Universitario Virgen Macarena
Sevilla , 41009, Spain
Beatson West of Scotland Cancer Centre
Glasgow , G12 0, United Kingdom
Barts Health NHS Trust - St Bartholomew's Hospital
London , EC1A , United Kingdom

How clear is this clinincal trial information?

Study is for people with:

Breast Cancer

Phase:

Phase 1

Estimated Enrollment:

280

Study ID:

NCT03424005

Recruitment Status:

Recruiting

Sponsor:


Hoffmann-La Roche

How clear is this clinincal trial information?

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