Metastatic Breast Cancer
Conditions
Keywords
Phase 3, trastuzumab, Breast Neoplasms
Brief summary
The current study will compare the efficacy, safety, pharmacokinetics and immunogenicity of PF-05280014 in combination with paclitaxel versus trastuzumab sourced from the European Union (trastuzumab-EU) with paclitaxel in female patients with HER2-positive, metastatic breast cancer in the first-line treatment setting. The hypothesis to be tested in this study is that the efficacy (ORR) of PF-05280014 is similar to trastuzumab-EU.
Interventions
BIOLOGICALPF-05280014
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
DRUGPaclitaxel
A nonaqueous solution intended for dilution with a suitable parenteral fluid prior to intravenous infusion. Paclitaxel is available in 30 mg (5 mL), 100 mg (16.7 mL), and 300 mg (50 mL) multidose vials. Each mL of sterile nonpyrogenic solution contains 6 mg paclitaxel. The starting dose of paclitaxel will be 80 mg/m\^2 by IV infusion over 60 minutes (duration of infusion may be modified according to local standard of care, if applicable). Provision is made for dose reduction to 70 mg/m\^2 and then 60 mg/m\^2 as needed. In the absence of disease progression in the judgment of the investigator or prohibitive toxicity, patients will receive treatment with paclitaxel for at least 6 cycles or until maximal benefit of response is obtained, in the judgment of the investigator.
BIOLOGICALHerceptin®
Concentrate for solution for infusion, sterile vial 150 mg. Initial dose of 4 mg/kg over 90 minutes (depending on tolerability) IV infusion, then 2 mg/kg over 30 to 90 minutes (depending on tolerability) IV infusion weekly until disease progression. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the Herceptin® regimen may be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed diagnosis of breast cancer. * Presence of metastatic disease. * Documentation of HER2 gene amplification or overexpression. * Available tumor tissue for central review of HER2 status. * At least 1 measurable lesion as defined by RECIST 1.1. * Eastern Cooperative Oncology Group status of 0 to 2. * Left ventricular ejection fraction within institutional range of normal, measured by either two dimensional echocardiogram or multigated acquisition scan.
Exclusion criteria
* Relapse within 1 year of last dose of previous adjuvant (including neoadjuvant) treatment (except endocrine therapy) and within 1 year before randomization. * Prior systemic therapy for metastatic disease (except endocrine therapy). * Prior cumulative dose of doxorubicin of \>400 mg/m2, epirubicin dose \>800 mg/m\^2, or the equivalent dose for other anthracyclines or derivatives (eg, 72 mg/m\^2 of mitoxantrone). If the patient has received more than one anthracycline, then the cumulative dose must not exceed the equivalent of 400 mg/m\^2 of doxorubicin. * Inflammatory breast cancer. * Active uncontrolled or symptomatic central nervous system metastases.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population | From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit | ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size \[short axis \<10 mm\]) or partial response (PR, \>=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population | From the date of randomization until 378 days post-randomization | One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method. |
| Duration of Response (DOR) Per Central Radiology Assessments: ITT Population | From the date of randomization until 378 days post-randomization | DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis \<10 mm. PR: \>=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method. |
| Overall Survival: ITT Population | From the date of randomization until end of study (approximately 6 years) | Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method. |
| Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population | 1 hour post end of infusion on Day 1 of Cycles 1 and 5 | Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA. |
| Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population | 1 hour post end of infusion on Day 1 of Cycles 1 and 5 | Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA). |
| Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 | Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA. |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17 | Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer \>=1.0) is provided. |
| Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population | Cycle 1 Day 1 (prior to treatment) | Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer \>=1.48) is provided. |
| Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5 | Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA. |
Countries
Argentina, Brazil, Chile, Czechia, Greece, Hungary, India, Japan, Latvia, Mexico, Peru, Philippines, Poland, Portugal, Romania, Russia, Serbia, Slovakia, South Africa, South Korea, Thailand, Turkey (Türkiye), Ukraine, United States
Participant flow
Recruitment details
A total of 707 participants were randomized to the study. Of these, 5 participants were randomized but did not receive the study drug.
Pre-assignment details
Participants who fulfilled the inclusion/exclusion criteria were randomly assigned to 1 of the 2 treatments of this study.
Participants by arm
| Arm | Count |
|---|---|
| PF-05280014 Participants with human epidermal growth factor receptor 2 (HER2)-positive breast cancer received PF-05280014 on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as intravenous (IV) infusions until the end of the study. The first infusion of PF-05280014 was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of PF-05280014 were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m\^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the PF-05280014 could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. | 349 |
| Trastuzumab-EU Participants with HER2-positive breast cancer received trastuzumab-EU on Days 1, 8, 15 and 22 of each 28-day cycle followed by paclitaxel on Days 1, 8 and 15 of each 28-day cycle both as IV infusions until the end of the study. The first infusion of trastuzumab-EU was 4 mg/kg over 90 minutes on Cycle 1 Day 1. Subsequent weekly infusions of trastuzumab-EU were 2 mg/kg over 30 to 90 minutes. Paclitaxel was administered at a dose of 80 mg/m\^2 over 60 minutes. Following completion of the paclitaxel administration period and beginning no earlier than Week 33 of the study, the trastuzuamab-EU could be changed at the discretion of the investigator to every 3 weeks at a dose of 6 mg/kg infused over 30 to 90 minutes depending on tolerability. | 353 |
| Total | 702 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 52 | 60 |
| Overall Study | Lost to Follow-up | 8 | 18 |
| Overall Study | No longer willing to participate in study | 26 | 26 |
| Overall Study | Other | 4 | 3 |
| Overall Study | Participants terminated from study by Sponsor | 26 | 30 |
| Overall Study | Protocol Violation | 2 | 1 |
Baseline characteristics
| Characteristic | PF-05280014 | Trastuzumab-EU | Total |
|---|---|---|---|
| Age, Customized <18 | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18 to 64 | 283 Participants | 292 Participants | 575 Participants |
| Age, Customized 65 to 84 | 66 Participants | 60 Participants | 126 Participants |
| Age, Customized ≥85 | 0 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Female | 349 Participants | 353 Participants | 702 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 61 / 349 | 67 / 353 |
| other Total, other adverse events | 337 / 349 | 334 / 353 |
| serious Total, serious adverse events | 67 / 349 | 69 / 353 |
Outcome results
Primary
Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population
ORR was defined as the percentage of participants who achieved complete response (CR, complete disappearance of all target lesions with the exception of nodal disease; all target nodes must have decreased to normal size \[short axis \<10 mm\]) or partial response (PR, \>=30% decrease from baseline of the sum of diameters (SOD) of all target measurable lesions; the short diameter was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions) by Week 25 of the study and confirmed on a follow-up assessment (Week 33+/-14 days), based on the assessments of the central radiology review in accordance with RECIST 1.1.
Time frame: From the date of randomization until all participants had either completed the Week 33 tumor assessment or discontinued study drug earlier than the Week 33 visit
Population: The ITT population was defined as all participants who were randomized to study drug.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PF-05280014 | Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population | 62.5 percentage of participants |
| Trastuzumab-EU | Objective Response Rate (ORR) Derived From Central Radiology Assessments: ITT Population | 66.5 percentage of participants |
Comparison: Risk Ratio and associated 95% confidence interval (CI) are unstratified and based on the Miettinen and Nurminen method.95% CI: [0.842, 1.049]
Secondary
Duration of Response (DOR) Per Central Radiology Assessments: ITT Population
DOR:time from first documentation of objective response (CR or PR) to first documentation of PD/death due to any cause in absence of documented PD, based on central radiology review. As per RECIST v1.1, CR:complete disappearance of all target lesions with exception of nodal disease; all target nodes reduced in short axis \<10 mm. PR: \>=30% decrease from baseline of SOD of target lesions; short diameter used in sum for target nodes,longest diameter used in sum for other target lesions. PD for target disease:at least 20% increase in SOD of target lesions above smallest sum observed (over baseline if no decrease in sum observed) with minimum absolute increase of 5 mm. For non-target disease:unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for median time to event was based on the Brookmeyer and Crowley method.
Time frame: From the date of randomization until 378 days post-randomization
Population: The ITT population was defined as all participants who were randomized to study drug. Here Overall number of participants analyzed signifies participants evaluable for this outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-05280014 | Duration of Response (DOR) Per Central Radiology Assessments: ITT Population | 11.27 months |
| Trastuzumab-EU | Duration of Response (DOR) Per Central Radiology Assessments: ITT Population | 10.58 months |
p-value: 0.30495% CI: [0.67, 1.27]Log Rank
Secondary
Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population
Two sensitive, specific, and semi-quantitative electrochemiluminescent (ECL) immunoassays, 1 for detecting antibodies against PF-05280014 and the other for detecting antibodies against trastuzumab, were used to analyze ADA samples. Serum samples were first screened for ADA. Any samples that were positive in the screening assay were further analyzed to confirm the positive result and determine the antibody titers. All samples were taken prior to dosing. The number of participants with a positive sample (titer \>=1.0) is provided.
Time frame: Pre-dose on Day 1 of Cycles 1, 3, 5, 8, 11, 14, 17
Population: Safety population was used for analysis, included all participants who received at least 1 dose of study drug. Here n signifies participants evaluable at specified time points only.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 1 Day 1 (prior to treatment) | 30 Participants |
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 3 Day 1 | 0 Participants |
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 5 Day 1 | 0 Participants |
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 8 Day 1 | 0 Participants |
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 11 Day 1 | 0 Participants |
| PF-05280014 | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 14 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 17 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 8 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 1 Day 1 (prior to treatment) | 14 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 14 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 3 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 11 Day 1 | 0 Participants |
| Trastuzumab-EU | Number of Participants With Positive Anti-Drug Antibodies (ADA) Sample: Safety Population | Cycle 5 Day 1 | 0 Participants |
Secondary
Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population
Human serum samples testing positive for the presence of ADA (anti-PF-05280014 or anti-trastuzumab-EU) were analyzed for the presence or absence of NAb (neutralizing anti-PF-05280014 or neutralizing anti-trastuzumab-EU antibodies) following a tiered approach using screening and titer determination. The number of participants at baseline (prior to treatment) with a positive NAb sample (titer \>=1.48) is provided.
Time frame: Cycle 1 Day 1 (prior to treatment)
Population: Safety population was used for analysis, included all participants who received at least 1 dose of study drug.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PF-05280014 | Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population | 20 Participants |
| Trastuzumab-EU | Number of Participants With Positive Neutralizing Antibodies (Nab) Prior to Treatment: Safety Population | 9 Participants |
Secondary
One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population
One-year PFS rate was analyzed based on the time from date of randomization to first documentation of progressive disease (PD), or death due to any cause in the absence of documented PD, based on the assessments of the central radiology review in accordance with RECIST 1.1. PD was defined for target disease as at least a 20% increase in sum of diameters of target measurable lesions above the smallest sum observed (over baseline if no decrease in the sum was observed during therapy) with a minimum absolute increase of 5 mm. For non-target disease: PD was defined as unequivocal progression of pre-existing lesions and if overall tumor burden increased sufficiently to merit discontinuation of therapy; appearance of any new unequivocal malignant lesion was also considered PD. The 95% CI for the median time to event was based on the Brookmeyer and Crowley method.
Time frame: From the date of randomization until 378 days post-randomization
Population: The ITT population was defined as all participants who were randomized to study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-05280014 | One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population | 12.16 months |
| Trastuzumab-EU | One-year Progression-Free Survival (PFS) Rate Derived From Central Radiology Assessments: ITT Population | 12.06 months |
p-value: 0.50595% CI: [0.8, 1.26]Log Rank
Secondary
Overall Survival: ITT Population
Overall survival was analyzed based on the time from date of randomization to the date of death due to any cause. Participants last known to be alive were censored on the date of last contact. The 95% CI for the median time to event was based on the Brookmeyer and Crowley Method.
Time frame: From the date of randomization until end of study (approximately 6 years)
Population: The ITT population was defined as all participants who were randomized to study drug.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PF-05280014 | Overall Survival: ITT Population | NA months |
| Trastuzumab-EU | Overall Survival: ITT Population | NA months |
p-value: 0.33995% CI: [0.656, 1.316]Log Rank
Secondary
Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population
Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific enzyme-linked immunosorbent assay (ELISA).
Time frame: 1 hour post end of infusion on Day 1 of Cycles 1 and 5
Population: PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here number analyzed (n) signifies participants evaluable at specified time points only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-05280014 | Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population | Cycle 1 Day 1 | 89.85 mcg/mL |
| PF-05280014 | Serum Peak Concentration of PF-05280014 at Selected Cycles: Pharmacokinetics (PK) Population | Cycle 5 Day 1 | 95.70 mcg/mL |
Secondary
Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time frame: 1 hour post end of infusion on Day 1 of Cycles 1 and 5
Population: PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here n signifies participants evaluable at specified time points only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-05280014 | Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 1 Day 1 | 89.70 mcg/mL |
| PF-05280014 | Serum Peak Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 5 Day 1 | 94.40 mcg/mL |
Secondary
Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population
Human PK serum samples were analyzed for concentrations of PF-05280014 using a validated, sensitive, and specific ELISA.
Time frame: Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Population: PK population.Here n signifies participants evaluable at specified time points only.The Cycle 17 Day 1 (C17D1) samples summarized previously at PCD (Week 33) fell outside of cut-off used for final analysis (Week 53), to limit data for up to 1-year post randomization, which was more conservative from previous Week 33 analysis. While comparing data between Week 33 and Week 53, there was a significant drop off in number of samples summarized at C17D1 and was down to zero for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 3 Day 1 | 48.20 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 1 Day 1 | 0.00 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 1 Day 8 | 27.90 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 4 Day 1 | 53.50 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 5 Day 1 | 57.00 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 5 Day 8 | 57.40 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 7 Day 1 | 60.50 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 8 Day 1 | 62.25 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 11 Day 1 | 54.65 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of PF-05280014 at Selected Cycles: PK Population | Cycle 14 Day 1 | 50.70 mcg/mL |
Secondary
Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population
Human PK serum samples were analyzed for concentrations of trastuzumab-EU using a validated, sensitive, and specific ELISA.
Time frame: Pre-dose on Day 1 of Cycles 1, 3, 4, 5, 7, 8, 11, 14, 17 and Day 8 of Cycles 1 and 5
Population: PK population was used for analysis, included all participants who received PF-05280014 or trastuzumab-EU and had no major protocol deviations that influenced PK assessments, and had at least 1 post dose concentration measurement. Here n signifies participants evaluable at specified time points only.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 1 Day 1 | 0.00 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 1 Day 8 | 29.80 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 3 Day 1 | 50.40 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 4 Day 1 | 54.35 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 5 Day 1 | 60.00 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 5 Day 8 | 61.20 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 7 Day 1 | 63.00 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 8 Day 1 | 65.55 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 11 Day 1 | 57.50 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 14 Day 1 | 54.60 mcg/mL |
| PF-05280014 | Serum Trough (Pre-dose) Concentration of Trastuzumab-EU at Selected Cycles: PK Population | Cycle 17 Day 1 | 45.10 mcg/mL |