Clinical Trial: NCT04740918 - My Cancer Genome

NCT04740918

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.

Related Conditions:

Breast Carcinoma

Recruiting Status:

Recruiting

Phase:

Phase 3

URL:

https://clinicaltrials.gov/show/NCT04740918

Trial Eligibility

Document

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

Metastatic Breast Cancer

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

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.	Trastuzumab Emtansine
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

Clinical Trials /

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)