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

Conditions

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

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Atezolizumab — 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 — 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 — DRUG
  Docetaxel 75 mg/m\^2 administered via IV infusion on Day 1 every 21-days for 6 cycles.
• Pertuzumab — DRUG
  Pertuzumab 840 mg loading dose then 420 mg administered via IV infusion on Day 1 of every 21-day cycle.
• Trastuzumab — 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 — 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).
• Doxorubicin — 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 — 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.

Study Details

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.

Key Dates

Start date

Dec 31, 2015

Status verified

Jan 2020

Primary completion

Nov 13, 2019

Completion

Nov 13, 2019

Study Design

Enrollment

98 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab
  Participants will receive atezolizumab in combination with trastuzumab and pertuzumab every 3 weeks.
• 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.
• 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.
• 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.
• 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.
• Experimental: Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel
  Participants will receive atezolizumab in combination with trastuzumab, pertuzumab, and docetaxel every 3 weeks.
• 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.
• 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.
• 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.
• 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.

Primary Outcome Measure

Percentage of Participants With Dose Limiting Toxicities (DLT) - Cohort 1A, 1B, 1C, 1D, 1F [ Time Frame: Baseline up to Day 21 ]

Locations (20)

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