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

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.

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.

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.

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.

The adverse event (AE) severity grading scale NCI CTCAE v5.0 was used for assessing AE severity. Any AEs for which the NCI CTCAE v5.0 did not provide a grading scale, the standard four-point scale from 1 to 4 (mild, moderate, severe, life-threatening) was used. The terms "severe" and "serious" are not synonymous and are independently assessed for each AE. Multiple occurrences of AEs were counted only once per participant at the highest (worst) grade. AEs to monitor included administration-related reactions, hypersensitivity and anaphylaxis, diarrhoea, rash, cardiac dysfunction, neutropenia or febrile neutropenia, mucositis, and interstitial lung disease.

Echocardiography was used to assess left ventricular ejection fraction (LVEF) values. The screening LVEF assessment had to be performed within ≤28 days prior to randomization and the LVEF value must have been ≥55% to be eligible for the study.

Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.

Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.

Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.

Vital sign measurements were taken after the participant had remained resting in a semi-supine position for at least 5 minutes. The minimum and maximum values are, respectively, the smallest and largest values obtained at any point after baseline, including any repeat and unscheduled measurements.

For safety monitoring purposes, the investigator was required to review, sign, and date all electrocardiogram (ECG) reports. Any morphologic waveform changes or other ECG abnormalities were documented by the investigator. Post-baseline, if all examinations were normal, then it was categorized as 'Normal'. If any abnormality was reported, then it was categorized as 'Abnormal'. 'Clinically significant' is a subset of the abnormal category.

Not every laboratory abnormality qualified as an adverse event. A laboratory test result had to be reported as an adverse event if it met any of the following criteria: was accompanied by clinical symptoms; resulted in a change in study treatment; resulted in a medical intervention or a change in concomitant therapy; was clinically significant in the investigator's judgment.

Pain intensity scores were assessed by the participants using the Visual Analog Scale (VAS) on a line measuring between 0 mm ('no pain') and 100 mm ('unbearable pain'). The VAS was completed in both study arms to assess the level of pain experienced by the participant in relation to the injection of Phesgo. On Day 1, pain assessments were performed prior to, during, and immediately after injection of Phesgo when the needle or device was removed, and 2 hours after injection.

Skin irritation and sensitization reactions at the site of injection caused by the adhesion of the OBDS to the skin were assessed by the study staff using the device monitoring questionnaire in the eCRF. Dermal effects were reported on a scale from 0 (no evidence or irritation) to 7 (strong reaction spreading beyond test site). Other effects were reported on a separate scale from 0 (no evidence) to 7 (small petechial eruptions or scabs).

Participants in the Phesgo OBDS arm completed the device monitoring questionnaire the injection with the OBDS. The questionnaire assessed the following criteria: ease of device attachment, attachment during the injection, ease of device removal, and overall wearing comfort, which were each rated on a three-point scale as "Good", "Acceptable", or "Poor".

Details of performance and ease of use of the on-body delivery system (OBDS) were reported by site staff, using the device monitoring questionnaire in the eCRF. This included the following: Preparation of the injection site, Preparation of the OBDS, Prefilled cartridge inspection before insertion in the OBDS, Positioning and attachment of the OBDS on the anterior thigh, Drug delivery, and OBDS administration failures.