NCT03726879|CompletedPhase 3ResultsDMCFDA Drug

A Study To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer

IMpassion050

A Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial To Evaluate the Efficacy and Safety Of Atezolizumab or Placebo in Combination With Neoadjuvant Doxorubicin + Cyclophosphamide Followed By Paclitaxel + Trastuzumab + Pertuzumab In Early Her2-Positive Breast Cancer

Hoffmann-La Roche ClinicalTrials.gov

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1 other identifier

BO40747

Study Type

interventional

Target

454

Locations

12 countries

Sites

Timeline

RegisteredNov 2018

StartedJan 2019

CompletionAug 2023

Brief Summary

This study (also known as IMpassion050) will evaluate the efficacy and safety of atezolizumab compared with placebo when given in combination with neoadjuvant dose-dense anthracycline (doxorubicin) + cyclophosphamide followed by paclitaxel + trastuzumab + pertuzumab (ddAC-PacHP) in patients with early HER2-positive breast cancer (T2-4, N1-3, M0).

Trial Health

On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment

454

participants targeted

Target at P50-P75 for phase_3 breast-cancer

Timeline

Completed

Started Jan 2019

Geographic Reach

12 countries

76 active sites

Status

completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

4.6 years study duration

First Submitted

Initial submission to the registry

October 30, 2018

Completed

2 days until next milestone

First Posted

Study publicly available on registry

November 1, 2018

Completed

2 months until next milestone

Study Start

First participant enrolled

January 11, 2019

Completed

2.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 5, 2021

Completed

1.1 years until next milestone

Results Posted

Study results publicly available

March 25, 2022

Completed

1.4 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 24, 2023

Completed

Last Updated

November 5, 2024

Status Verified

October 1, 2024

Enrollment Period

2.1 years

First QC Date

October 30, 2018

Results QC Date

January 21, 2022

Last Update Submit

October 11, 2024

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (2)

Percentage of Participants With Pathological Complete Response (pCR) in the PD-L1-Positive Population (IC 1/2/3)
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer \[AJCC\] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (estrogen receptor (ER) positive and/or progesterone receptor (PgR) positive vs. ER negative and PgR negative).
From randomization to approximately 6 months
pCR in the ITT Population
pCR is defined as the absence of residual invasive cancer on hematoxylin and eosin evaluation of the complete resected breast specimen and all sampled regional lymph nodes following completion of neoadjuvant systemic therapy (NAST) (i.e., ypT0/is ypN0 in the current American Joint Committee on Cancer \[AJCC\] staging system, 8th edition). Treatment comparison was made using Cochran-Mantel-Haenszel test stratified by disease stage (T2 vs. T3-4) and hormone receptor status (ER positive and/or PgR positive vs. ER negative and PgR negative).
From randomization to approximately 6 months

Secondary Outcomes (21)

Percentage of Participants With pCR Based on Hormone Receptor Status
From randomization to approximately 24 months
Percentage of Participants With pCR in the PD-L1-Negative Population
From randomization to approximately 24 months
Event-Free Survival (EFS)
From randomization to first documented disease recurrence, unequivocal tumor progression determined by the treating investigator, or death from any cause (up to approximately 54 months)
Disease-Free Survival (DFS)
Time from surgery to first documented disease recurrence or death from any cause (up to approximately 54 months)
Overall Survival (OS)
From randomization to date of death from any cause (up to approximately 54 months)
+16 more secondary outcomes

Study Arms (2)

Atezolizumab +ddAC-PacHP

EXPERIMENTAL

Participants will receive atezolizumab (atezo) 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by atezo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8mg/kg IV loading dose) Q3W for 4 cycles, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant and adjuvant setting: atezo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezo+trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL dated 3 Feb 2021 treatment with atezo must be discontinued.

Drug: AtezolizumabDrug: DoxorubicinDrug: CyclophosphamideDrug: PaclitaxelDrug: TrastuzumabDrug: PertuzumabDrug: Trastuzumab Emtansine

Placebo + ddAC-PacHP

PLACEBO COMPARATOR

Participants will receive placebo 840 mg IV Q2W for 4 cycles during neoadjuvant phase with ddAC (doxorubicin 60 mg/m2 \& cyclophosphamide 600 mg/m2 IV), followed by placebo 1200 mg IV Q3W for 4 cycles with paclitaxel 80 mg/m2 IV weekly for 12 continuous weeks, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W for 4 cycles \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W for 4 cycles. During adjuvant phase, participants will continue to receive following study treatments Q3W to complete up to 1 year HER2-target therapy inclusive of therapy given both in neoadjuvant \& adjuvant setting: placebo 1200 mg IV Q3W, trastuzumab 6 mg/kg IV (with initial 8-mg/kg IV loading dose) Q3W, \& pertuzumab 420 mg IV (with initial 840-mg IV loading dose) Q3W. Participants who do not achieve pCR have option of receiving blinded atezolizumab + trastuzumab emtansine post surgery for 14 cycles. In response to USM DIL, dated 3 Feb 2021 treatment with placebo must be discontinued.

Drug: PlaceboDrug: DoxorubicinDrug: CyclophosphamideDrug: PaclitaxelDrug: TrastuzumabDrug: PertuzumabDrug: Trastuzumab Emtansine

Interventions

AtezolizumabDRUG

Atezolizumab will be administered as per the schedule specified in the respective arm.

Also known as: Tecentriq

Atezolizumab +ddAC-PacHP

PlaceboDRUG

Placebo matched to atezolizumab will be administered as per the schedule specified in the respective arm.

Placebo + ddAC-PacHP

DoxorubicinDRUG

Doxorubicin will be administered as per the schedule specified in the respective arm.

Also known as: Adriamycin