A Study in Healthy Male Subjects to Investigate the Comparability of Pharmacokinetics of the Fixed-Dose Combination of Pertuzumab and Trastuzumab Administered Subcutaneously Using a Handheld Syringe or Using the On-Body Delivery System

NCT05275010 | Completed Phase 1 Results FDA Drug

• 1 other identifier: WP42873
• Study Type: interventional
• Target: 151
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a randomized, open-label, 2-arm, parallel-group, single-dose, multi-center study in healthy male subjects to investigate the comparability of the pharmacokinetics of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using the proprietary on-body delivery system or a handheld syringe with hypodermic needle.

Conditions

Healthy Male Subjects

Outcome Measures

Primary Outcomes (4)

• Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Pertuzumab

  For the analysis of AUC0-62days, participants in the Per Protocol Pharmacokinetics (PK) Analysis Population (PAP) with missing Day 63 PK pertuzumab concentration data or with a Day 63 PK sample time deviation outside a +/-120-hour window of planned sampling time were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.

  Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63

• Area Under the Time-Concentration Curve From the Start of Dosing to 63 Days (AUC0-62) for Serum Trastuzumab

  For the analysis of AUC0-62days, participants in the Per Protocol Pharmacokinetics (PK) Analysis Population (PAP) with missing Day 63 PK trastuzumab concentration data or with a Day 63 PK sample time deviation outside a +/-120-hour window of planned sampling time were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.

  Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63

• Maximum Serum Concentration (Cmax) of Pertuzumab

  For analysis of Cmax, participants from the Per Protocol PK Analysis Population (PAP) with two or more missing PK pertuzumab concentration data on any of Days 3, 5, 7, 9 or 11 were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.

  Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63

• Maximum Serum Concentration (Cmax) of Trastuzumab

  For analysis of Cmax, participants from the Per Protocol PK Analysis Population (PAP) with two or more missing PK trastuzumab concentration data on any of Days 3, 5, 7, 9 or 11 were excluded. Participants were excluded from the PAP for the following reasons: 1. The participant violates inclusion or exclusion criteria regarding body mass index (BMI), use of prohibited medications and concomitant subcutaneous, intravenous (IV), or any parenteral drugs, participation in an investigational drug or device study, current chronic daily treatment with corticosteroids, and receipt of IV antibiotics for infection. 2. An SC injection site other than thigh is used; 3. Any participant whose injection is not successfully performed.

  Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63

Secondary Outcomes (26)

• Observed Serum Concentration of Pertuzumab on Day 22

  Day 22

• Observed Serum Concentration of Trastuzumab on Day 22

  Day 22

• Observed Serum Concentration of Pertuzumab on Day 63

  Day 63

• Observed Serum Concentration of Trastuzumab on Day 63

  Day 63

• Area Under the Time-Concentration Curve From the Start of Dosing Extrapolated to Infinity (AUC0-∞) for Serum Pertuzumab

  Predose (0 hour) and 2, 6, and 12 hours postdose on Day 1, and postdose on Days 2, 3, 5, 7, 9, 11, 15, 22, 35, 49, and 63

Study Arms (2)

Arm 1: PH FDC SC Using a Handheld Syringe

ACTIVE COMPARATOR

A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using a handheld syringe with hypodermic needle.

Drug: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC); Device: Handheld Syringe with Hypodermic Needle

Arm 2: PH FDC SC Using the OBDS

EXPERIMENTAL

A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the participant's anterior thigh on Day 1, using the on-body delivery system (OBDS).

Drug: Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC); Device: On-Body Delivery System

Interventions

Fixed-Dose Combination of Pertuzumab and Trastuzumab SC (PH FDC SC) DRUG

A single dose of PH FDC SC (600 mg pertuzumab/600 mg trastuzumab) will be administered by a healthcare professional subcutaneously (SC) into the anterior thigh, using either a handheld syringe with hypodermic needle (Arm 1) or the on-body delivery system (Arm 2).

Also known as: Pertuzumab, Trastuzumab, and Hyaluronidase-zzxf, PHESGO®, RO7198574, RG6264

Arm 1: PH FDC SC Using a Handheld Syringe; Arm 2: PH FDC SC Using the OBDS

Handheld Syringe with Hypodermic Needle DEVICE

A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using a handheld manual syringe.

Arm 1: PH FDC SC Using a Handheld Syringe

On-Body Delivery System DEVICE

A single 10-mL dose of PH FDC SC will be administered as a subcutaneous (SC) injection using the on-body delivery system (OBDS).

Arm 2: PH FDC SC Using the OBDS

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy male subjects age 18-45 years at time of signing Informed Consent Form
• Ability to comply with the study protocol
• Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, during the treatment period and for 7 months after the dose of PH FDC SC
• A body mass index (BMI) between 18 and 32 kilograms per metre squared (kg/m2), inclusive
• Intact normal skin without potentially obscuring tattoos, pigmentation, or lesions in the area for intended injection on the thighs
• Baseline LVEF≥55% measured by echocardiogram (ECHO)
• No history of hypersensitivity or confirmed, clinically significant and clinically relevant allergic reactions, either spontaneously or following any drug administration
• No history of any clinically significant and clinically relevant cardiac condition
• No history of previous anticancer treatments including pertuzumab, trastuzumab, anthracyclines, or any cardiotoxic drugs
• No apparent family history of clinically significant and clinically relevant hypersensitivity, allergy, and severe cardiac diseases
• No contraindications from detailed medical and surgical history and physical examinations
• No previous enrollment in this study protocol and no concurrent enrollment in any other study protocol

You may not qualify if:

• Positive urine test for drugs of abuse as per local standard (for alcohol abuse, positive breath test is also acceptable)
• Positive test result for hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) 1 or 2, showing: History of exposure to HBV, HCV, or HIV; or Active viral hepatitis infection (HBV or HCV) or HIV infection
• Systolic blood pressure ≥140 millimetres of mercury (mmHg) or \<90 mmHg, or diastolic blood pressure \>90 mmHg or \<50 mmHg
• Use of prohibited medications including non-prescription medications, nutraceuticals, nutritional supplements or any herbal remedies taken within 10 days or 5 times the elimination half-life (whichever is longer) prior to randomization into the study
• Concomitant subcutaneous, intravenous, or any parenteral drugs within 90 days prior to screening
• Participation in an investigational drug or device study within 90 days or five times the elimination half-life (whichever is longer) prior to screening
• Donation of blood over 500 millilitres (mL) within 3 months prior to enrollment
• Known severe hypersensitivity to plaster, medical adhesive tapes, or bandages
• Known allergy to murine proteins, hyaluronidase, bee, or vespid venom, or any other ingredient in the formulation of rHuPH20 (Hylenex® recombinant \[hyaluronidase human injection\]) or any other ingredients and excipients in the formulation of PH FDC SC
• Clinically significant abnormalities in laboratory test results (including hepatic and renal panels, CBC, chemistry panel, and urinalysis)
• Clinically relevant electrocardiogram abnormalities at screening or Day -1
• History of any cardiac condition
• Lower extremity edema or pathology (e.g., cellulitis, lymphatic disorder or prior surgery, pre-existing pain syndrome, previous lymph node dissection etc.) that could interfere with any protocol-specified outcome assessment
• Any history of clinically significant and clinically relevant allergies, oncologic, psychiatric, gastrointestinal, renal, hepatic, cardiovascular or pulmonary disease
• Concomitant disease or condition that could interfere with, or for which the treatment might interfere with, the conduct of the study, or that would pose an unacceptable risk to the subject in this study

Sponsors & Collaborators

• Hoffmann-La Roche: lead

Study Sites (5)

Q-Pharm Pty Ltd; Nucleus Network Brisbane Clinic

Herston, Queensland, 4006, Australia

Location

CMAX Pty Ltd

Adelaide, South Australia, 5000, Australia

Location

Linear Clinical Research Ltd

Nedlands, Western Australia, 6009, Australia

Location

New Zealand Clinical Research - Auckland

Auckland, 1010, New Zealand

Location

New Zealand Clinical Research - Christchurch

Christchurch, 8011, New Zealand

Location

Related Publications (1)

• Wynne C, Wang B, Deng R, Li J, Eiger D, Bene Tchaleu F, Heeson S, Restuccia E. Pharmacokinetic bioequivalence of the fixed-dose combination of pertuzumab and trastuzumab administered subcutaneously using a handheld syringe or an on-body delivery system. J Cancer Res Clin Oncol. 2025 Jun 14;151(6):188. doi: 10.1007/s00432-025-06228-4.

  PMID: 40514611 DERIVED

MeSH Terms

Interventions

pertuzumab; Trastuzumab; Needles

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Equipment and Supplies

Results Point of Contact

• Title: Medical Communications
• Organization: Hoffmann-La Roche

genentech@druginfo.com

800-821-8590

Study Officials

• Clinical Trials

  Hoffmann-La Roche

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 2, 2022
• First Posted: March 11, 2022
• Study Start: May 30, 2022
• Primary Completion: May 14, 2023
• Study Completion: October 3, 2023
• Last Updated: September 23, 2024
• Results First Posted: September 23, 2024

Record last verified: 2024-04

Data Sharing

• IPD Sharing: Will not share

Locations

NZ (2); AU (3)