A Study Comparing Atezolizumab (Anti PD-L1 Antibody) In Combination With Adjuvant Anthracycline/Taxane-Based Chemotherapy Versus Chemotherapy Alone In Patients With Operable Triple-Negative Breast Cancer (IMpassion030)

Roche

Status and phase: Terminated; Phase 3

Conditions: Triple Negative Breast Cancer

Treatments: Drug: Cyclophosphamide; Drug: Dose-dense Doxorubicin or dose-dense Epirubicin; Drug: Atezolizumab; Drug: Paclitaxel

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03498716

AFT-27 (Other Identifier)

WO39391

BIG 16-05 (Other Identifier)

ALEXANDRA (Other Identifier)

2016-003695-47 (EudraCT Number)

Details and patient eligibility

About

This study will evaluate the efficacy, safety, and pharmacokinetics of adjuvant atezolizumab in combination with paclitaxel, followed by atezolizumab, dose-dense doxorubicin or epirubicin (investigator's choice), and cyclophosphamide, compared with paclitaxel followed by dose-dense doxorubicin or epirubicin (investigator's choice) and cyclophosphamide alone in patients with Stage II-III TNBC (Triple Negative Breast Cancer)

Enrollment: 2,199 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

• Non-metastatic operable Stage II-III breast cancer
• Histologically documented TNBC (Triple Negative Breast Cancer)
• Confirmed tumor PD-L1 evaluation as documented through central testing of a representative tumor tissue specimen
• Adequately excised: Patients must have undergone either breast-conserving surgery or mastectomy/nipple- or skin-sparing mastectomy
• Adequate hematologic and end-organ function
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive measures and agreement to refrain from donating sperm.
• No more than 8 weeks (56 days) may elapse between definitive breast surgery and randomization.
• Representative formalin-fixed, paraffin embedded (FFPE) tumor specimen from surgical resection in paraffin blocks (preferred) or at least 25 unstained slides.

Exclusion Criteria

• Prior history of invasive breast cancer
• For the currently diagnosed breast cancer, any previous systemic anti-cancer treatment (e.g., neoadjuvant or adjuvant), including, but not limited to, chemotherapy, anti-HER2 therapy.
• Previous therapy with anthracyclines or taxanes for any malignancy
• Cardiopulmonary dysfunction
• Prior malignancies within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death and treated with expected curative outcome
• Active or history of autoimmune disease or immune deficiency
• History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest computed tomography (CT) scan
• Urinary outflow obstruction
• Active tuberculosis
• Major surgical procedure other than for diagnosis within 4 weeks prior to initiation of study treatment or anticipation of need for a major surgical procedure during study treatment or within 5 months following the last dose of Atezolizumab (for patients randomized to Atezolizumab)
• Prior allogeneic stem cell or solid organ transplant
• Treatment with systemic immunosuppressive medications within 2 weeks prior to initiation of study treatment or anticipation of need for systemic immunosuppressive medication during the study

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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2,199 participants in 2 patient groups

Atezolizumab + Chemotherapy

Experimental group

Description:

Participants will receive atezolizumab (in combination with chemotherapy as described below) every 2 weeks for 10 doses, followed by atezolizumab maintenance therapy every 3 weeks to complete 1 year of treatment from the first dose Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Treatment:

Drug: Paclitaxel

Drug: Atezolizumab

Drug: Dose-dense Doxorubicin or dose-dense Epirubicin

Drug: Cyclophosphamide

Chemotherapy

Active Comparator group

Description:

Chemotherapy will consist of paclitaxel every week for 12 weeks, followed by dose-dense doxorubicin +cyclophosphamide or dose-dense epirubicin + cyclophosphamide every 2 weeks, for 4 doses supported with Granulocyte Colony-Stimulating Factor (G-CSF) or Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF)

Treatment:

Drug: Paclitaxel

Drug: Dose-dense Doxorubicin or dose-dense Epirubicin

Drug: Cyclophosphamide