Phase 3
N=333
A Study to Investigate Atezolizumab and Chemotherapy Compared With Placebo and Chemotherapy in the Neoadjuvant Setting in Participants With Early Stage Triple Negative Breast Cancer
Triple-negative Breast Cancer
Bottom Line
View on ClinicalTrials.gov: NCT03197935 ↗Enrolled (actual)
333
Serious AEs
28.7%
Results posted
Jun 2021
Primary outcome: Primary: Number of Participants With Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population — 69; 95 Number of Participants — p=0.0044
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Atezolizumab (MPDL3280A), an engineered anti-PDL1 antibody (Drug); Placebo (Drug); Nab-paclitaxel (Drug); Doxorubicin (Drug); Cyclophosphamide (Drug); Filgrastim (Drug); Pegfilgrastim (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Apr 2020
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Pathologic Complete Response (pCR) Using American Joint Committee on Cancer (AJCC) Staging System in ITT Population |
69; 95 | 0.0044 sig |
| PRIMARY Number of Participants With pCR in Subpopulation With PD-L1-Positive Tumor Status (Tumor-infiltrating Immune Cell [IC] 1/2/3) Using AJCC Staging System |
37; 53 | 0.0206 sig |
| SECONDARY Event-Free Survival (EFS) in All Participants |
NA; NA | — |
| SECONDARY Event-Free Survival (EFS) in Subpopulation With PD-L1-Postive Tumor Status |
NA; NA | — |
| SECONDARY Disease-Free Survival (DFS) in All Participants Who Undergo Surgery |
NA; NA | — |
| SECONDARY Disease-Free Survival (DFS) in Subpopulation of Participants With PD-L1-Positive Tumor Status Who Undergo Surgery |
NA; NA | — |
| SECONDARY Overall Survival (OS) in All Participants |
NA; NA | — |
| SECONDARY Overall Survival (OS) in Subpopulation With PD-L1-Positive Tumor Status |
NA; NA | — |
| SECONDARY Mean Scores for Function (Role/Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30 |
76.45; 79.24; 71.90; 71.55; 65.30; 62.65 | — |
| SECONDARY Mean Change From Baseline Scores for Function (Role, Physical) and GHS/HRQoL by Cycle and Between Treatment Arms as Assessed by the EORTC QLQ-C30 |
-4.62; -7.91; -12.72; -17.07; -14.49; -19.80 | — |
| SECONDARY Percentage of Participants With at Least One Adverse Events (AEs) |
100; 100 | — |
| SECONDARY Minimum Observed Serum Atezolizumab Concentration (Cmin) |
142; 189; 207; 78.7; 204; 267 | — |
| SECONDARY Maximum Observed Serum Atezolizumab Concentration (Cmax) |
334 | — |
| SECONDARY Percentage of Participants With Anti-Drug Antibodies (ADAs) to Atezolizumab |
2.5; 13.4 | — |
Summary
This is a global Phase III, double-blind, randomized, placebo-controlled study designed to evaluate the efficacy and safety of neoadjuvant treatment with atezolizumab (anti-programmed death-ligand 1 [anti-PD-L1] antibody) and nab-paclitaxel followed by doxorubicin and cyclophosphamide (nab-pac-AC), or placebo and nab-pac-AC in participants eligible for surgery with initial clinically assessed triple-negative breast cancer (TNBC).
Eligibility Criteria
Inclusion criteria
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically documented TNBC (negative human epidermal growth factor receptor 2 [HER2], estrogen receptor [ER], and progesterone receptor [PgR] status)
- Confirmed tumor programmed death-ligand 1 (PD-L1) evaluation as documented through central testing of a representative tumor tissue specimen
- Primary breast tumor size of greater than (>) 2 centimeters (cm) by at least one radiographic or clinical measurement
- Stage at presentation: cT2-cT4, cN0-cN3, cM0
- Participant agreement to undergo appropriate surgical management including axillary lymph node surgery and partial or total mastectomy after completion of neoadjuvant treatment
- Baseline left ventricular ejection fraction (LVEF) greater than or equal to (>=) 53 percent (%) measured by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans
- Adequate hematologic and end-organ function
- Representative formalin-fixed, paraffin-embedded (FFPE) tumor specimen in paraffin blocks (preferred) or at least 20 unstained slides, with an associated pathology report documenting ER, PgR, and HER2 negativity
- For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs
- 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 or have undergone a sterilization procedure must have a negative serum pregnancy test result within 14 days prior to initiation of study drug
Exclusion criteria
- Prior history of invasive breast cancer
- Stage 4 (metastatic) breast cancer
- Prior systemic therapy for treatment and prevention of breast cancer
- Previous therapy with anthracyclines or taxanes for any malignancy
- History of ductal carcinoma in situ (DCIS), except for participants treated exclusively with mastectomy >5 years prior to diagnosis of current breast cancer
- History of pleomorphic lobular carcinoma in situ (LCIS), except for participants surgically managed >5 years prior to diagnosis of current breast cancer
- Bilateral breast cancer
- Undergone incisional and/or excisional biopsy of primary tumor and/or axillary lymph nodes
- Axillary lymph node dissection prior to initiation of neoadjuvant therapy
- History of other malignancy within 5 years prior to screening, with the exception of those with a negligible risk of metastasis or death
- Cardiopulmonary dysfunction
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
- Known allergy or hypersensitivity to the components of the formulations of atezolizumab, nab-paclitaxel, cyclophosphamide, or doxorubicin, filgrastim or pegfilgrastim
- Active or history of autoimmune disease or immune deficiency diseases except history of autoimmune-related hypothyroidism, controlled Type 1 diabetes mellitus, and dermatologic manifestations of eczema, psoriasis, lichen simplex chronicus, or vitiligo (e.g., participants with psoriatic arthritis are excluded)
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, 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
- Positive human immunodeficiency virus (HIV) test at screening
- Active hepatitis B and hepatitis C virus infection
- Active tuberculosis
- Severe infections within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
- Treatment with therapeutic oral or IV antibiotics within 2 weeks prior to initiati
Data sourced from ClinicalTrials.gov (NCT03197935). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.