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

Roche

Status and phase: Completed; Phase 1

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

Treatments: Drug: Docetaxel; Drug: Carboplatin; Drug: Pertuzumab; Drug: Atezolizumab; Drug: Doxorubicin; Drug: Cyclophosphamide; Drug: Trastuzumab; Drug: Trastuzumab emtansine

Study type: Interventional

Funder types: Industry

Identifiers

NCT02605915

GO29831

2015-002113-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 98 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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98 participants in 10 patient groups

Cohort 1A: Atezolizumab/Trastuzumab/Pertuzumab

Experimental group

Description:

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

Treatment:

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Pertuzumab

Cohort 1B: Atezolizumab/Trastuzumab emtansine 3.6 mg

Experimental group

Description:

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

Treatment:

Drug: Trastuzumab emtansine

Drug: Atezolizumab

Cohort 1C: Atezolizumab/Trastuzumab emtansine 3.0 mg

Experimental group

Description:

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

Treatment:

Drug: Trastuzumab emtansine

Drug: Atezolizumab

Cohort 1D: Atezolizumab/Trastuzumab emtansine 2.4 mg

Experimental group

Description:

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

Treatment:

Drug: Trastuzumab emtansine

Drug: Atezolizumab

Cohort 1E: Atezolizumab/ doxorubicin/ cyclophosphamide

Experimental group

Description:

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.

Treatment:

Drug: Doxorubicin

Drug: Atezolizumab

Drug: Cyclophosphamide

Cohort 1F: Atezolizumab/Trastuzumab/Pertuzumab/ Docetaxel

Experimental group

Description:

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

Treatment:

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Pertuzumab

Drug: Docetaxel

Cohort 2A: Atezolizumab/Trastuzumab/Pertuzumab

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Pertuzumab

Drug: Docetaxel

Drug: Carboplatin

Cohort 2B: Atezolizumab/Trastuzumab emtansine

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab emtansine

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Pertuzumab

Drug: Docetaxel

Drug: Carboplatin

Cohort 2C: Safety Expansion

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab emtansine

Drug: Atezolizumab

Cohort 2D: Safety Expansion

Experimental group

Description:

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.

Treatment:

Drug: Trastuzumab

Drug: Atezolizumab

Drug: Pertuzumab