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

A Phase I, Open-Label, Two-Part, Multicenter Perjeta® Subcutaneous Dose-Finding Study in Combination With Herceptin® in Healthy Male Volunteers and Female Patients With Early Breast Cancer

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.

Study Overview

• Status: Completed
• Conditions: Early Breast Cancer
• Intervention / Treatment: Drug: Pertuzumab; Drug: Trastuzumab

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1142
    • Auckland Clinical Studies
  • Christchurch, New Zealand, 8011
    • Christchurch Clinical Studies Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

11

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Part 1-Cohort 1: Pertuzumab 420 Milligrams (mg) IV; Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 420 mg IV.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451
EXPERIMENTAL: Part 1-Cohort 2: Pertuzumab 400 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 400 mg SC.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451
EXPERIMENTAL: Part 1-Cohort 3: Pertuzumab 600 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 600 mg SC.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451
EXPERIMENTAL: Part 1-Cohort 4: Pertuzumab 1200 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of pertuzumab 1200 mg SC.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451
ACTIVE_COMPARATOR: Part 1-Cohort 5: Trastuzumab 600 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of trastuzumab 600 mg SC.	Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 1-Cohort 6: Pertuzumab 400 mg SC + Trastuzumab 600 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 400 mg and trastuzumab 600 mg SC.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 1-Cohort 7: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; Part 1 includes healthy male participants. Participants will receive a single injection of co-mixed pertuzumab 1200 mg and trastuzumab 600 mg SC.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 1-Cohort 8: Pertuzumab 1200 mg SC + Trastuzumab 600 mg SC; 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.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 2-Cohort A: Pertuzumab SC + Trastuzumab SC; 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.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 2-Cohort B: Pertuzumab SC + Trastuzumab SC; 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.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317
EXPERIMENTAL: Part 2-Cohort C: Pertuzumab SC + Trastuzumab SC; 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.	Drug: Pertuzumab; Participants will receive pertuzumab as a single agent injection, co-mixed or formulated as FDC with trastuzumab depending upon cohort. The dose will range from 400 to 1200 mg.; Other Names: Perjeta, RO4368451; Drug: Trastuzumab; Participants will receive a single dose of trastuzumab 600 mg SC separately, co-mixed or co-formulated with pertuzumab.; Other Names: Herceptin, RO0452317

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area Under the Concentration from Time Zero to Time Infinity (AUC0-inf) of Pertuzumab SC	Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Maximum Serum Concentration (Cmax) of Pertuzumab SC	Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Time to Reach Cmax (Tmax) of Pertuzumab SC	Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
Minimum Serum Concentration (Cmin) of Pertuzumab SC	Pre-dose (0 hours) and 6, 8, and 12 hours post-dose on Day 1; on Days 2, 3, 5, 8, 10, 15, 22, 43, 85; and at follow-up visit (up to approximately 24 months)
AUC0-inf of Pertuzumab IV	Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Cmax of Pertuzumab IV	Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Tmax of Pertuzumab IV	Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)
Cmin of Pertuzumab IV	Pre-dose (0 hours) and 1.5 and 3 hours post-dose on Day 1; on Days 2, 3, 5, 8, 15, 22, 35, 43, 85; and at follow-up visit (up to approximately 24 months)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants with Adverse Events	Baseline up to approximately 24 months
Percentage of Participants with Anti-Therapeutic Antibodies (ATAs) to Pertuzumab	Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Percentage of Participants with ATAs to Trastuzumab	Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)
Percentage of Participants with ATAs to rHuPH20	Baseline, Day 22, Day 85, and 7 months post-dose (up to approximately 24 months overall)

Collaborators and Investigators

• Sponsor: Hoffmann-La Roche

Publications and helpful links

General Publications

• Kirschbrown WP, Wynne C, Kagedal M, Wada R, Li H, Wang B, Nijem I, Badovinac Crnjevic T, Gasser H, Heeson S, Eng-Wong J, Garg A. Development of a Subcutaneous Fixed-Dose Combination of Pertuzumab and Trastuzumab: Results From the Phase Ib Dose-Finding Study. J Clin Pharmacol. 2019 May;59(5):702-716. doi: 10.1002/jcph.1362. Epub 2018 Dec 19.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 23, 2016
• Primary Completion (ACTUAL): May 31, 2018
• Study Completion (ACTUAL): May 31, 2018

Study Registration Dates

• First Submitted: March 29, 2016
• First Submitted That Met QC Criteria: April 11, 2016
• First Posted (ESTIMATE): April 14, 2016

Study Record Updates

• Last Update Posted (ACTUAL): June 12, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Trastuzumab; Pertuzumab
• Other Study ID Numbers: BO30185

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No