Safety and Pharmacokinetics of Atezolizumab Combination Treatments in Participants With HER2-Positive and HER2-Negative Breast Cancer

NCT ID: NCT02605915

Last Updated: 2020-02-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 98 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-12-31
• Study Completion Date: 2019-11-13

Brief Summary

This is a Phase Ib, open-label, two-stage study with two active regimens in each stage designed to evaluate the safety and tolerability of combination treatment with atezolizumab, trastuzumab, and pertuzumab (with and without docetaxel) or atezolizumab and trastuzumab emtansine in participants with human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer (MBC) and locally advanced early breast cancer (EBC), and atezolizumab with doxorubicin and cyclophosphamide in HER2-negative breast cancer.

Conditions

HER2-Positive Metastatic Breast Cancer; HER2-Negative Metastatic Breast Cancer; Locally Advanced or Early Breast Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab

Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg

Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg

Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg

Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide

Participants with HER2-negative breast cancer will receive atezolizumab (every 2 weeks) in combination with doxorubicin (every 2 weeks) and cyclophosphamide for four cycles. After the completion of four cycles of combination atezolizumab /doxorubicin / cyclophosphamide, atezolizumab will be continued as a single-agent at a dose of 1200 mg every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Doxorubicin

Intervention Type: DRUG

Doxorubicin will be administered at 60 mg/m\^2 every 2 weeks as an IV bolus over 3 to 5 minutes or as an infusion over 15 to 30 minutes.

Cyclophosphamide

Intervention Type: DRUG

Cyclophosphamide will be administered at 600 mg/m\^2 on Day 1 of each 21 day cycle as an IV bolus over 3 to 5 minutes or as an infusion, in accordance with local policy.

Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel

Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab

Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered at an initial target of area under the curve (AUC) of 6 milligrams per milliliter\*min (mg/mL\*min) via an IV infusion on Day 1 of every 21-days for 6 cycles.

Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Cohort 2B: Atezolizumab/Trastuzumab emtansine

Participants will receive atezolizumab in combination with trastuzumab emtansine every 3 weeks for 2 cycles, followed by docetaxel, carboplatin, trastuzumab and pertuzumab every 3 weeks for 6 cycles. Breast surgery will be performed no later than 6 weeks after neoadjuvant therapy. Upon the completion of surgery, participants will receive 12 cycles of single-agent trastuzumab every 3 weeks.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Carboplatin

Intervention Type: DRUG

Carboplatin will be administered at an initial target of area under the curve (AUC) of 6 milligrams per milliliter\*min (mg/mL\*min) via an IV infusion on Day 1 of every 21-days for 6 cycles.

Docetaxel

Intervention Type: DRUG

Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Cohort 2C: Safety Expansion

Participants with HER2-positive metastatic breast cancer/unresectable locally advanced breast cancer who received prior treatment with trastuzumab and a taxane chemotherapy will receive atezolizumab in combination with trastuzumab emtansine at the dose determined from stage 1, every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Trastuzumab emtansine

Intervention Type: DRUG

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Cohort 2D: Safety Expansion

Participants with HER2-positive metastatic breast cancer recently progressed on an HP containing regimen will receive atezolimumab in combination with trastuzumab and pertuzumab every 3 weeks until disease progression, lack of clinical benefit, or unacceptable toxicity.

Group Type: EXPERIMENTAL

Atezolizumab

Intervention Type: DRUG

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Pertuzumab

Intervention Type: DRUG

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Trastuzumab

Intervention Type: DRUG

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Interventions

Atezolizumab

Atezolizumab 1200 milligrams (mg) or 840 mg (Cohort 1E only) flat dose administered via intravenous (IV) infusion on Day 1 of every 21-day cycle.

Intervention Type: DRUG

Carboplatin

Carboplatin will be administered at an initial target of area under the curve (AUC) of 6 milligrams per milliliter\*min (mg/mL\*min) via an IV infusion on Day 1 of every 21-days for 6 cycles.

Intervention Type: DRUG

Docetaxel

Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.

Intervention Type: DRUG

Pertuzumab

Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.

Intervention Type: DRUG

Trastuzumab

Trastuzumab 8 milligram per kilogram (mg/kg) loading dose, then 6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle.

Intervention Type: DRUG

Trastuzumab emtansine

Trastuzumab emtansine 3.6 mg/kg administered via IV infusion on Day 1 of every 21-day cycle. Dose de-escalation may occur for trastuzumab emtansine, from the full trastuzumab emtansine dose at 3.6 mg/kg on Day 1 of every 21-day cycle, potentially to 3.0 mg/kg (Cohort 1C) or 2.4 mg/kg q3w (Cohort 1D).

Intervention Type: DRUG

Doxorubicin

Doxorubicin will be administered at 60 mg/m\^2 every 2 weeks as an IV bolus over 3 to 5 minutes or as an infusion over 15 to 30 minutes.

Intervention Type: DRUG

Cyclophosphamide

Cyclophosphamide will be administered at 600 mg/m\^2 on Day 1 of each 21 day cycle as an IV bolus over 3 to 5 minutes or as an infusion, in accordance with local policy.

Intervention Type: DRUG

Other Intervention Names

Tecentriq, RO5541267; RO4368451; RO0452317; RO5304020

Eligibility Criteria

Inclusion Criteria

• Histologically documented HER2-positive and HER2-negative (cohort E only) breast cancer
• Metastatic breast cancer that is measurable (Stage 1) or early breast cancer with a primary tumor size greater than (>) 2 centimeter (cm) (Stage 2)
• Eastern cooperative oncology group (ECOG) performed status of 0, 1 or 2; 0 or 1 (cohort E only)
• Life expectancy of 12 or more weeks
• Adequate hematologic and end-organ function
• Left ventricular ejection fraction greater than or equal to (>=) 50 percentage (%); >=55% (cohort E only)

Exclusion Criteria

• Known central nervous system (CNS) disease, except for treated asymptomatic CNS metastases
• Leptomeningeal disease
• Pregnancy or lactation
• History of autoimmune disease
• Prior allogeneic stem cell or solid organ transplantation
• Positive test for human immunodeficiency virus (HIV)
• Active hepatitis B or hepatitis C

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hoffmann-La Roche

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clinical Trials

Role: STUDY_DIRECTOR

Hoffmann-La Roche

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of Arkansas for Medical Sciences; Winthrop Rockefeller Cancer Institute

Little Rock, Arkansas, United States

Joliet oncology hematology associates

Joliet, Illinois, United States

Horizon Oncology Research, Inc.

Lafayette, Indiana, United States

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, United States

Karmanos Cancer Center; Department of Oncology

Detroit, Michigan, United States

HCA Midwest Division

Kansas City, Missouri, United States

Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart

The Bronx, New York, United States

Levine Cancer Institute

Charlotte, North Carolina, United States

Duke Cancer Center

Durham, North Carolina, United States

Oncology Hematology Care Inc

Cincinnati, Ohio, United States

St. Luke's University Health Network

Bethlehem, Pennsylvania, United States

Kimmel Cancer Center Thomas Jefferson University

Philadelphia, Pennsylvania, United States

Magee Womens Hospital

Pittsburgh, Pennsylvania, United States

Tennessee Oncology - Chattanooga; Tennessee Oncology - East Third Street

Chattanooga, Tennessee, United States

West Clinic

Germantown, Tennessee, United States

Tennessee Oncology

Nashville, Tennessee, United States

MD Anderson Cancer Center

Houston, Texas, United States

Cancer Therapy and Research Center CTRC at UTHSCSA

San Antonio, Texas, United States

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Countries

United States

Other Identifiers

2015-002113-29

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

GO29831

Identifier Type: -

Identifier Source: org_study_id