Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other names:
    • RO4368451
  • 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.
    Other names:
    • RO0452317
Experimental
Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg
Participants will receive atezolizumab in combination with trastuzumab emtansine (3.6 mg/kg) every 3 weeks.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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).
    Other names:
    • RO5304020
Experimental
Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg
Participants will receive atezolimumab in combination with trastzumab emtansine (3.0 mg/kg) every 3 weeks.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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).
    Other names:
    • RO5304020
Experimental
Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg
Participants will receive atezolimumab in combination with trastzumab emtansine (2.4 mg/kg) every 3 weeks.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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).
    Other names:
    • RO5304020
Experimental
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.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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.
  • 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.
Experimental
Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • Drug: Docetaxel
    Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other names:
    • RO4368451
  • 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.
    Other names:
    • RO0452317
Experimental
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.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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.
  • Drug: Docetaxel
    Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other names:
    • RO4368451
  • 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.
    Other names:
    • RO0452317
Experimental
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.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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.
  • Drug: Docetaxel
    Docetaxel 75 mg/m^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other names:
    • RO4368451
  • 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.
    Other names:
    • RO0452317
  • 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).
    Other names:
    • RO5304020
Experimental
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.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • 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).
    Other names:
    • RO5304020
Experimental
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.
  • Drug: 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.
    Other names:
    • Tecentriq, RO5541267
  • Drug: Pertuzumab
    Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
    Other names:
    • RO4368451
  • 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.
    Other names:
    • RO0452317

Recruiting Locations

Montefiore Medical Center, Advanced Women's Health Center, Clinical Trials and Research Unit; Depart
Bronx, New York 10461

More Details

NCT ID
NCT02605915
Status
Recruiting
Sponsor
Hoffmann-La Roche

Study Contact

Reference Study ID Number: GO29831 www.roche.com/about_roche/roche_worldwide.htm
888-662-6728 (U.S. and Canada)
global-roche-genentech-trials@gene.com

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.