A Study of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo as a Treatment for Participants With Human Epidermal Growth Factor 2 (HER2)-Positive and Programmed Death-ligand 1 (PD-L1)-Positive Locally Advanced (LABC) or Metastatic Breast Cancer (MBC)

Phase 3TerminatedNCT04740918

Hoffmann-La Roche96 enrolled

Overview

This study will evaluate the efficacy, safety and patient-reported outcomes of trastuzumab emtansine plus atezolizumab compared with trastuzumab emtansine plus placebo in participants with HER2-positive and PD-L1-positive LABC or MBC.Participants must have progressed either during or after prior trastuzumab- (+/- pertuzumab) and taxane-based therapy for LABC/MBC; or during (or within 6 months after completing) trastuzumab- (+/-pertuzumab) and taxane-based therapy in the neoadjuvant and/or adjuvant setting.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Enrollment

Conditions

Metastatic Breast Cancer

Interventions

Trastuzumab Emtansine

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * HER2+ and PD-L1+ locally advanced (LABC) or metastatic breast cancer (MBC) * Progression must have occurred during most recent treatment for LABC/MBC or during, or within 6 months after completing, neoadjuvant and/or adjuvant therapy * Prior treatment with trastuzumab (+/- pertuzumab) and taxane in the neoadjuvant and/or adjuvant, locally advanced, or metastatic setting * No more than two prior lines of therapy in the metastatic setting * Measurable disease per RESIST version 1.1 * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Life expectancy \>= 6 months * Adequate hematologic and end-organ function * For women of childbearing potential: agreement to remain abstinent or use contraception, and agreement to refrain from donating eggs * For men: agreement to remain abstinent or use contraceptive measures, and agreement to refrain from donating sperm Exclusion Criteria: * Prior treatment with trastuzumab emtansine in metastatic setting * History of exposure to cumulative doses of anthracyclines * Symptomatic or actively progressing central nervous system (CNS) metastases; asymptomatic CNS lesions ≤ 2cm without clinical requirement for local intervention or asymptomatic patients with treated CNS lesions are eligible * Current Grade \>= 3 peripheral neuropathy * Cardiopulmonary dysfunction * History of malignancy within 5 years prior to initiation of study treatment, with the exception of the cancer under investigation and malignancies with a negligible risk of metastasis or death * History of leptomeningeal disease * Active or history of autoimmune disease or immune deficiency * Active hepatitis B, hepatitis C and/or tuberculosis * Prior allogeneic stem cell or solid organ transplantation * Receipt of a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, during treatment, or within 5 months following the last dose of study treatment * Pregnancy or lactation

Locations (51)

Emad Ibrahim, Md, Inc

Redlands, California, United States

Peter MacCallum Cancer Center

Melbourne, Victoria, Australia

Hospital Sao Rafael - HSR

Salvador, Estado de Bahia, Brazil

Hospital do Cancer de Pernambuco - HCP

Recife, Pernambuco, Brazil

Oncosite - Centro de Pesquisa Clinica Em Oncologia Ltda

Ijuí, Rio Grande do Sul, Brazil

Outcomes

Primary Outcomes

Progression-Free Survival (PFS) as Determined by Investigator Using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1)

PFS was defined as the time from randomization to the first occurrence of documented disease progression (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 in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 millimeter (mm). Median PFS was calculated using the Kaplan-Meier (KM) methodology. Data for participants without PD or death from any cause as of the data cut-off date were censored at the time of the last tumor assessment.

Time frame: Up to 28 months

Overall Survival (OS)

OS was defined as the time from the first dose of study treatment to the time of death from any cause. Participants who are alive as of the data cut-off date of the analysis were censored at the last known date they were alive. Participants with no post-baseline information were censored at the date of randomization plus 1 day. Median OS was calculated using the KM methodology.

Time frame: Up to 28 months

Secondary Outcomes

Objective Response Rate (ORR)

ORR was defined as the percentage of participants with complete response (CR) or partial response (PR) on two consecutive assessments, at least 28 days apart, as determined by the investigator using RECIST v.1.1. CR was defined as the disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR was defined as at least a 30% decrease in the sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. Only participants with measurable disease at baseline were analyzed for this outcome measure. Participants without a post-baseline tumor assessment were considered non-responders. An estimate of the ORR and its 95% CI (Wilson score confidence interval) were calculated for each treatment arm.

Time frame: Up to 28 months

Duration of Response (DOR)

DOR was calculated for participants who had a best OR of CR/PR. DOR was defined as time from first occurrence of a documented OR until the time of documented PD or death from any cause, whichever occurs first as determined by investigator assessment using RECIST v1.1. CR=the disappearance of all target lesions or any pathological lymph nodes (whether target or non-target) having a reduction in short axis to \<10 mm. PR=at least a 30% decrease in the SOD of target lesions, taking as reference the baseline SOD. PD=at least a 20% increase in the SOD of target lesions, taking as reference the smallest sum on the study including baseline (nadir). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median DOR was calculated using the KM methodology.

Time frame: Up to 28 months

PFS in Participants With Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1

PFS was defined as the time from randomization to the first occurrence of documented 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 in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology.

Time frame: Up to 28 months

OS in Participants With Baseline Brain Metastases

OS is defined as the time from the first dose of study treatment to the time of death from any cause. Median OS was calculated using the KM methodology.

Time frame: Up to 28 months

Central Nervous System (CNS) PFS as Determined by Investigator Using RECIST v1.1 in Participants With Baseline CNS Metastases

CNS PFS was defined as the time from randomization to the first occurrence of documented CNS PD, or first occurrence of symptomatic CNS disease 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 in the study, including baseline, in addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. Median PFS was calculated using the KM methodology. Participants who experienced non-CNS PD at the time of analysis were censored at the date of this progression. Participants who experienced no PD and were alive at the time of analysis were censored at date of their last post-baseline tumor assessment or, if they had no post-baseline tumor assessment, on the date of randomization + 1 day.

Time frame: Up to 28 months

CNS PFS as Determined by Investigator Using RECIST v1.1 in Participants Without Baseline CNS Metastases

Time frame: Up to 28 months

Percentage of Participants With Adverse Events (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), symptom, or disease temporally associated with the use of a pharmaceutical product, whether or not considered related to the pharmaceutical product.

Time frame: Up to 28 months