Triple-Negative Breast Cancer
Conditions
Brief 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.
Interventions
DRUGAtezolizumab
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.
DRUGNab-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.
Sponsors
Hoffmann-La Roche
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open label, non-blinded
Intervention model description
This is an open-label (non-blinded), single arm safety study in which all participants will receive atezolizumab in combination with nab-paclitaxel.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Treatment-emergent Grade ≥3 Adverse Events (AEs) | Up to 60 months | AE=untoward medical occurrence in participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable & unintended sign, symptom/disease temporally associated with the use of pharmaceutical product, whether/not considered related to it. Severity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. Percentages have been rounded off. |
| Percentage of Participants With Treatment-emergent Grade ≥2 Immune-mediated AEs (imAEs) | Up to 60 months | AE=any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable and unintended sign, symptom/disease temporally associated with the use of a pharmaceutical product, whether/not considered related to it. Severity was graded according to NCI CTCAE v5.0. Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care ADL; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. imAEs are events that resemble autoimmune diseases and are known side effects of immune checkpoint inhibitors. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall Survival (OS) in Safety-evaluable Population | Up to 60 months | OS was defined as time from initiation of study treatment to death from any cause. OS was estimated using Kaplan-Meier (K-M) method. |
| OS in PD-L1-positive Population | Up to 60 months | OS was defined as time from initiation of study treatment to death from any cause. OS was estimated using K-M method. |
| Percentage of Participants With All Treatment-emergent AEs | Up to 60 months | An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the PP. Percentages have been rounded off. |
| PFS in PD-L1-positive Population | Up to 60 months | PFS was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 mm. PFS was estimated using K-M method. |
| Progression Free Survival (PFS) in Safety-evaluable Population | Up to 60 months | PFS was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 millimeters (mm). PFS was estimated using K-M method. |
| Percentage of Participants With All Treatment-emergent Serious Adverse Events (SAEs) | Up to 60 months | An AE was any untoward medical occurrence in a participant administered a PP and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the PP. SAEs were defined as any AE that fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. Percentages have been rounded off. |
Countries
Argentina, Chile, Czechia, France, Hungary, Italy, Mexico, Peru, Poland, Portugal, Romania, Slovenia, Spain
Participant flow
Recruitment details
Participants with unresectable locally advanced or metastatic programmed death-ligand 1 (PD-L1)-positive Triple-Negative Breast Cancer (TNBC) took part in the study at 67 centers in 13 countries from 10 Dec 2019 to 15 Dec 2024.
Pre-assignment details
Participants received atezolizumab in combination with nab-paclitaxel until disease progression (PD) or unacceptable toxicity or loss of clinical benefit. A total of 184 participants were enrolled in the study. However, two participants discontinued the study before receiving any treatment. Hence, participant flow data is presented for 182 participants. All protocol-specified assessments were completed as planned. Hence, this study was considered to be completed.
Participants by arm
| Arm | Count |
|---|---|
| Atezolizumab + Nab-paclitaxel Participants received atezolizumab 840 mg as IV infusion on Days 1 and 15 of each 28-day cycle along with nab-paclitaxel, 100 mg/m\^2 as IV infusion on Days 1, 8 and 15 of each 28-day cycle until PD, unacceptable toxicity, loss of clinical benefit or participant or investigator decision to discontinue treatment. | 182 |
| Total | 182 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Death | 104 |
| Overall Study | Lost to Follow-up | 5 |
| Overall Study | Study Ended by Sponsor | 56 |
| Overall Study | Withdrawal by Subject | 17 |
Baseline characteristics
| Characteristic | Atezolizumab + Nab-paclitaxel |
|---|---|
| Age, Continuous | 54.8 years STANDARD_DEVIATION 12.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 40 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 126 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 16 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 17 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) White | 146 Participants |
| Sex: Female, Male Female | 182 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 104 / 182 |
| other Total, other adverse events | 167 / 182 |
| serious Total, serious adverse events | 30 / 182 |
Outcome results
Primary
Percentage of Participants With Treatment-emergent Grade ≥2 Immune-mediated AEs (imAEs)
AE=any untoward medical occurrence in a participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable and unintended sign, symptom/disease temporally associated with the use of a pharmaceutical product, whether/not considered related to it. Severity was graded according to NCI CTCAE v5.0. Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living (ADL); Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care ADL; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. imAEs are events that resemble autoimmune diseases and are known side effects of immune checkpoint inhibitors.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel). Percentages have been rounded off.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Percentage of Participants With Treatment-emergent Grade ≥2 Immune-mediated AEs (imAEs) | 12.09 percentage of participants |
Primary
Percentage of Participants With Treatment-emergent Grade ≥3 Adverse Events (AEs)
AE=untoward medical occurrence in participant administered a pharmaceutical product, regardless of causal attribution. AE=any unfavorable & unintended sign, symptom/disease temporally associated with the use of pharmaceutical product, whether/not considered related to it. Severity was graded per National Cancer Institute Common Terminology Criteria for Adverse Events version 5.0 (NCI CTCAE v5.0). Grade 1=Mild; asymptomatic/mild symptoms; clinical/diagnostic observations only; or intervention not indicated; Grade 2=Moderate; minimal, local/non-invasive intervention indicated; or limiting age-appropriate instrumental activities of daily living; Grade 3=Severe/medically significant, but not immediately life-threatening; hospitalization/prolongation of hospitalization indicated; disabling; or limiting self-care activities of daily living; Grade 4=Life-threatening consequences/urgent intervention indicated; Grade 5=Death related to AE. Percentages have been rounded off.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Percentage of Participants With Treatment-emergent Grade ≥3 Adverse Events (AEs) | 46.70 percentage of participants |
Secondary
OS in PD-L1-positive Population
OS was defined as time from initiation of study treatment to death from any cause. OS was estimated using K-M method.
Time frame: Up to 60 months
Population: PD-L1 positive population included all participants with centrally confirmed PD-L1 positive tumor status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | OS in PD-L1-positive Population | NA months |
Secondary
Overall Survival (OS) in Safety-evaluable Population
OS was defined as time from initiation of study treatment to death from any cause. OS was estimated using Kaplan-Meier (K-M) method.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Overall Survival (OS) in Safety-evaluable Population | 27.0 months |
Secondary
Percentage of Participants With All Treatment-emergent AEs
An AE was any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the PP. Percentages have been rounded off.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Percentage of Participants With All Treatment-emergent AEs | 95.60 percentage of participants |
Secondary
Percentage of Participants With All Treatment-emergent Serious Adverse Events (SAEs)
An AE was any untoward medical occurrence in a participant administered a PP and which does not necessarily have to have a causal relationship with the treatment. An AE can therefore be any unfavorable and unintended sign (including abnormal laboratory values or abnormal clinical test results), symptoms, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the PP. SAEs were defined as any AE that fulfilled any of the following criteria: fatal (resulted in death), life-threatening, required in-patient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability/incapacity, was a congenital anomaly/ birth defect, was medically significant or required intervention to prevent any of the other outcomes listed here. Percentages have been rounded off.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Percentage of Participants With All Treatment-emergent Serious Adverse Events (SAEs) | 16.48 percentage of participants |
Secondary
PFS in PD-L1-positive Population
PFS was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to RECIST v1.1, or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 mm. PFS was estimated using K-M method.
Time frame: Up to 60 months
Population: PD-L1 positive population included all participants with centrally confirmed PD-L1 positive tumor status.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | PFS in PD-L1-positive Population | 11.1 months |
Secondary
Progression Free Survival (PFS) in Safety-evaluable Population
PFS was defined as the time from initiation of study treatment to the first occurrence of PD, as determined by the investigator according to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death from any cause, whichever occurs first. PD was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum of diameters at prior timepoints (including baseline), and must also demonstrate an absolute increase of ≥ 5 millimeters (mm). PFS was estimated using K-M method.
Time frame: Up to 60 months
Population: Safety-evaluable population included all enrolled participants who had received at least one dose of any study treatment (atezolizumab/nab-paclitaxel).
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atezolizumab + Nab-paclitaxel | Progression Free Survival (PFS) in Safety-evaluable Population | 7.4 months |