A Dose-Finding Study of Pertuzumab (Perjeta) in Combination With Trastuzumab (Herceptin) in Healthy Male Participants and Women With Early Breast Cancer (EBC)

Roche

Status and phase: Completed; Phase 1

Conditions: Early Breast Cancer

Treatments: Drug: Trastuzumab; Drug: Pertuzumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT02738970

BO30185

Details and patient eligibility

About

This study involves a two-part design. Part 1 is designed to determine the optimal dose of subcutaneous (SC) Perjeta, injected alone or mixed with Herceptin, that results in comparable exposure to intravenous (IV) Perjeta. Exposure between SC Perjeta and IV Perjeta will be compared using a compilation of pharmacokinetic (PK) parameters such as area under the concentration-time curve (AUC), maximum serum concentration (Cmax), time of maximum concentration (Tmax), and serum trough concentration (Ctrough). Part 2 is designed to confirm the dosing regimen in women with EBC on the basis of safety, tolerability, and PK assessments.

Enrollment: 88 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Part 1: Healthy male volunteers 18 to 45 years of age
• Part 1: Left ventricular ejection fraction (LVEF) at least 55 percent (%)
• Part 1: Body mass index (BMI) 18 to 32 kilograms per meter-squared (kg/m^2)
• Part 1: Normal, intact skin without tattoos or lesions in the injection area
• Part 2: Females at least 18 years of age
• Part 2: Eastern Cooperative Oncology Group (ECOG) performance status of 0
• Part 2: Previously treated, non-metastatic carcinoma of the breast
• Part 2: Baseline LVEF at least 55%
• Part 2: Negative pregnancy test and use of adequate contraceptive measures among women of childbearing potential

Exclusion criteria

• Part 1: Positive urine test for drugs of abuse
• Part 1: History of exposure or active viral infection of Hepatitis B, hepatitis C, or human immunodeficiency virus (HIV)
• Part 1: Cardiac disease including hypertension or hypotension
• Part 1: Lower extremity edema
• Part 1: Any clinically relevant history of systemic disease
• Part 1: History of breast cancer
• Part 1: Chronic corticosteroid use
• Part 1: Receipt of IV antibiotics within 7 days prior to enrollment
• Part 2: Concurrent malignancy requiring therapy that may interfere with pharmacokinetic investigations, or history of other malignancy within 5 years prior to Screening
• Part 2: Significant cumulative exposure to anthracyclines
• Part 2: Serious cardiac disease including uncontrolled hypertension
• Part 2: Poor hematologic, renal, or hepatic function
• Part 2: Pregnant or lactating women
• Part 2: History of exposure or active viral infection of Hepatitis B, hepatitis C, or HIV
• Part 2: Chronic corticosteroid use
• Part 2: Receipt of IV antibiotics within 7 days prior to enrollment

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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88 participants in 11 patient groups

Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV

Active Comparator group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV.

Treatment:

Drug: Pertuzumab

Part 1-Cohort 2: Pertuzumab 400 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC.

Treatment:

Drug: Pertuzumab

Part 1-Cohort 3: Pertuzumab 600 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC.

Treatment:

Drug: Pertuzumab

Part 1-Cohort 4: Pertuzumab 1200 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC.

Treatment:

Drug: Pertuzumab

Part 1-Cohort 5: Trastuzumab 600 mg SC

Active Comparator group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC.

Treatment:

Drug: Trastuzumab

Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC

Experimental group

Description:

Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC without recombinant human hyaluronidase (rHuPH20) excipient.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC

Experimental group

Description:

Part 2 includes women with early breast cancer. Cohort A will be enrolled only if FDC of pertuzumab and trastuzumab is not feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC administered separately. The dose of pertuzumab will be identified during Part 1.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC

Experimental group

Description:

Part 2 includes women with early breast cancer. Cohorts B and C will be enrolled if FDC of pertuzumab and trastuzumab is feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC; both agents administered in one injection (co-mixed). The dose of pertuzumab will be identified during Part 1.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab

Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC

Experimental group

Description:

Part 2 includes women with early breast cancer. Cohorts B and C will be enrolled if FDC of pertuzumab and trastuzumab is feasible. Participants will receive pertuzumab and trastuzumab (600 mg) SC; both agents formulated together and administered in one injection (FDC). The dose of pertuzumab will be identified during Part 1.

Treatment:

Drug: Pertuzumab

Drug: Trastuzumab