Description:
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.
Title
- Brief Title: 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)
- Official Title: A Randomized, Multicenter, Double-Blind, Placebo-Controlled Phase III Study of the Efficacy and Safety of Trastuzumab Emtansine in Combination With Atezolizumab or Placebo in Patients With HER2-Positive and PD-L1-Positive Locally Advanced or Metastatic Breast Cancer Who Have Received Prior Trastuzumab- (+/- Pertuzumab) and Taxane-Based Therapy (KATE3)
Clinical Trial IDs
- ORG STUDY ID:
MO42319
- SECONDARY ID:
2020-002818-41
- NCT ID:
NCT04740918
Conditions
Interventions
Drug | Synonyms | Arms |
---|
Trastuzumab Emtansine | Kadcyla, T-DM1, RO5304020 | Arm A: Trastuzumab Emtansine and Placebo |
Atezolizumab | Tecentriq, RO5541267, MPDL3280A | Arm B: Trastuzumab Emtansine and Atezolizumab |
Purpose
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.
Trial Arms
Name | Type | Description | Interventions |
---|
Arm A: Trastuzumab Emtansine and Placebo | Active Comparator | Placebo matched to atezolizumab followed by trastuzumab emtansine 3.6 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the sponsor. | |
Arm B: Trastuzumab Emtansine and Atezolizumab | Experimental | Atezolizumab 1200 mg IV infusion followed by trastuzumab emtansine 3.6 mg/kg IV infusion on Day 1 Cycle 1 and thereafter on Day 1 of each 21-day cycle until disease progression, unmanageable toxicity, or study termination by the Sponsor. | - Trastuzumab Emtansine
- Atezolizumab
|
Eligibility Criteria
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
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Progression-Free Survival (PFS) as Determined by Investigator's Assessment Using Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (v1.1) |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Percentage of Participants With Objective Response Rate (ORR) as Determined by Investigator's Assessment Using RECIST v1.1 |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Duration of Objective Response (DOR) as Determined by Investigator Assessment Using RECIST v1.1 |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | PFS as Determined by a Blinded Independent Central Review Committee Using RECIST v1.1 |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | PFS in Participants with Baseline Brain Metastases as Determined by Investigator Assessment Using RECIST v1.1 |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | OS in Participants with Baseline Brain Metastases |
Time Frame: | From baseline until death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Central Nervous System (CNS) PFS as Determined by Investigator Assessment Using RECIST v1.1 in Participants with or Without Baseline CNS Metastases |
Time Frame: | Baseline until disease progression, death or end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Mean Absolute Scores in Function (Physical, Role) and Global Health Status (GHS)/Quality of Life (QoL) as Measured by the European Organisation for Research and Treatment of Cancer (EORTC QLQ-C30) |
Time Frame: | From Cycle 1 until 3 months after study completion |
Safety Issue: | |
Description: | |
Measure: | Mean Change-From-Baseline Scores in Function (Physical, Role) and GHS/QoL as Measured by the EORTC QLQ-C30 |
Time Frame: | From Cycle 1 until 3 months after study completion |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Clinically Meaningful Deterioration in GHS/QoL Physical, and Role Function as Measured by the EORTC QLQ-C30 |
Time Frame: | From Cycle 1 until 3 months after study completion |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants with Adverse Events (AEs) According to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 |
Time Frame: | Baseline up to end of study (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Maximum Serum Concentration (Cmax) of Trastuzumab Emtansine |
Time Frame: | Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Cmax of Atezolizumab |
Time Frame: | Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With Anti-Drug Antibodies (ADAs) to Trastuzumab Emtansine |
Time Frame: | Day 1 of Cycles 1, 2 and 4 (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) |
Safety Issue: | |
Description: | |
Measure: | Percentage of Participants With ADAs to Atezolizumab |
Time Frame: | Day 1 of Cycles 1, 2, 3, 4 and 8 and every 8 cycles thereafter (each cycle=21 days) and during study treatment completion/early discontinuation visit (approximately 78 months) |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | Hoffmann-La Roche |
Last Updated
August 20, 2021