Metastatic Breast Cancer
Conditions
Keywords
HER2-positive breast cancer, MBC, Trastuzumab emtansine, Herceptin, T-DM1
Brief summary
This is a phase I, multicenter, open-label, dose-escalation study of single-agent trastuzumab-MCC-DM1 administered by intravenous (IV) infusion in patients with HER2-positive metastatic breast cancer (MBC) who have previously received trastuzumab. The study will assess the safety, tolerability, and pharmacokinetics of trastuzumab-MCC-DM1 and determine the dose and schedule to be used in Phase II.
Interventions
Intravenous escalating dose
Sponsors
Genentech, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Histologically documented, incurable, locally advanced or metastatic breast cancer * Evaluable or measurable HER2-positive disease * History of progression during or within 60 days after treatment with any prior trastuzumab-containing chemotherapy regimen for HER2-positive breast cancer * Previous treatment with chemotherapy for MBC * Granulocyte count ≥ 1,500/μL, platelet count ≥ 100,000/μL, and hemoglobin ≥ 9 g/dL * Serum bilirubin ≤ 1.5 mg/dL; AST, ALT, and alkaline phosphatase ≤ 2.5 × upper limit of normal (ULN) except for: Patients with hepatic metastases: ALT and AST ≤ 5 × ULN Patients with hepatic and/or bone metastases: alkaline phosphatase ≤ 5 × ULN * Serum creatinine ≤ 1.5 mg/dL or creatinine clearance of ≥ 60 mL/min based on a 24-hour urine collection * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2 * Women of childbearing potential and men must agree to use an effective method of birth control (e.g., hormonal, barrier) while receiving study treatment
Exclusion criteria
* History of significant cardiac disease, unstable angina, CHF, myocardial infarction, or ventricular arrhythmia requiring medication * History of Grade ≥ 3 hypersensitivity reaction to trastuzumab * History of any toxicity to trastuzumab that resulted in trastuzumab being permanently discontinued * Symptomatic brain metastases or any radiation or surgery for brain metastases within 3 months of first study treatment * Require supplemental oxygen for daily activities * Grade ≥ 2 peripheral neuropathy * Bisphosphonate therapy for symptomatic hypercalcemia * Any chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or biologic therapy for the treatment of breast cancer within 4 weeks of first study treatment * Any experimental therapy within 4 weeks of first study treatment * Any major surgical procedure within 4 weeks of first study treatment * History of clinically symptomatic liver disease, including viral or other hepatitis, current or history of alcoholism, or cirrhosis * Pregnancy or lactation * Cardiac troponin I ≥ 0.2 ng/mL * Ejection fraction \< 50% or below the lower limit of normal determined by echocardiogram or MUGA scan * Prior cumulative doxorubicin dose of \> 360 mg/m2 or equivalent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 | Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma. |
| Number of Patients With Dose Limiting Toxicities (DLTs) | A minimum of 21 days after first dose of trastuzumab-MCC-DM1 | DLT is defined as one of the following as per investigator related to study drug: * Grade ≥ 3 non-hematologic, non-hepatic major organ toxicity * Grade ≥ 3 cardiac toxicity, including cardiac troponin I elevation or any new segmental wall abnormality as determined by non-invasive cardiac imaging * Grade ≥ 4 thrombocytopenia * Grade ≥ 4 neutropenia (absolute neutrophil count \< 500/μ L) lasting \> 4 days or accompanied by fever * Grade ≥ 4 anemia * Grade ≥ 3 serum bilirubin, hepatic transaminase (alanine aminotransferase or aspartate aminotransferase), or alkaline phosphatase For patients with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver metastases or bone metastases, a hepatic transaminase or alkaline phosphatase level ≥ 10 times the upper limit of normal will be considered a DLT. * Weekly cohorts only: Toxicity preventing retreatment on Cycle 1, Day 8 or toxicity preventing re-treatment on Cycle 1, Days 15 and Day 22 |
| Maximum Tolerated Dose (MTD) | A minimum of 21 days after first dose of trastuzumab-MCC-DM1 | The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD. |
| Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 | — |
| PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18 | — |
| Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | Study treatment initiation until 30 or 90 days after last administration of study treatment | The time frame for AEs is study treatment initiation until 30 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first. The time frame for SAEs is study treatment initiation until 90 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Objective Response | Baseline to the end of the study (up to 3 years 2 months) | Duration of objective response was defined as the time from the initial response to disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine. |
| Progression-free Survival | Baseline to the end of the study (up to 3 years 2 months) | Progression-free survival was defined as the time from first dose of trastuzumab emtansine to documented disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine, whichever occurred earlier. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter of target lesions recorded since treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions. |
| Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine | Baseline to the end of the study (up to 3 years 2 months) | After the start of trastuzumab emtansine treatment, serum samples were collected every 3 weeks prior to trastuzumab emtansine dosing for detection of anti-therapeutic antibodies using a validated assay. A bridging antibody electrochemiluminescence assay (ECLA) was used to detect antibodies to trastuzumab emtansine. The assay utilized trastuzumab emtansine conjugated to biotin and a ruthenium label to form a complex with anti-trastuzumab emtansine antibodies. The antibody complex was captured by streptavidin-coated paramagnetic beads. |
| Percentage of Participants With an Objective Response | Baseline to the end of the study (up to 3 years 2 months) | The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions. |
Participant flow
Recruitment details
Approximately four centers in the United States were to participate in the study to enroll approximately 50-60 patients. Between 25 April 2006 and 20 May 2008, 54 patients were enrolled and 52 were treated.
Pre-assignment details
Two patients enrolled but discontinued the study prior to receiving study treatment drug, thus 52 patients received at least one dose and are included in the baseline and safety analysis data.
Participants by arm
| Arm | Count |
|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.3 mg/kg administered intravenously (IV) once every 3 weeks | 3 |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 0.6 mg/kg administered intravenously (IV) once every 3 weeks | 1 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once every 3 weeks | 1 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once every 3 weeks | 1 |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 3.6 mg/kg administered intravenously (IV) once every 3 weeks | 15 |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks Trastuzumab-MCC-DM1 4.8 mg/kg administered intravenously (IV) once every 3 weeks | 3 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly Trastuzumab-MCC-DM1 1.2 mg/kg administered intravenously (IV) once a week | 3 |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly Trastuzumab-MCC-DM1 1.6 mg/kg administered intravenously (IV) once a week | 3 |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly Trastuzumab-MCC-DM1 2.0 mg/kg administered intravenously (IV) once a week | 3 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly Trastuzumab-MCC-DM1 2.4 mg/kg administered intravenously (IV) once a week | 16 |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly Trastuzumab-MCC-DM1 2.9 mg/kg administered intravenously (IV) once a week | 3 |
| Total | 52 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 1 | 0 | 2 | 1 |
| Overall Study | Clinical progression | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | Dose limiting toxicity | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| Overall Study | Lack of Efficacy | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 | 2 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Progressive disease | 3 | 1 | 0 | 0 | 10 | 1 | 0 | 2 | 1 | 9 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 60.7 Years STANDARD_DEVIATION 10.1 | 47.0 Years STANDARD_DEVIATION 0 | 61.0 Years STANDARD_DEVIATION 0 | 58.0 Years STANDARD_DEVIATION 0 | 52.1 Years STANDARD_DEVIATION 10.3 | 48.0 Years STANDARD_DEVIATION 6 | 55.3 Years STANDARD_DEVIATION 10 | 53.0 Years STANDARD_DEVIATION 6.1 | 55.3 Years STANDARD_DEVIATION 3.2 | 50.9 Years STANDARD_DEVIATION 14 | 58.3 Years STANDARD_DEVIATION 11 | 52.9 Years STANDARD_DEVIATION 10.7 |
| Region of Enrollment United States | 3 participants | 1 participants | 1 participants | 1 participants | 15 participants | 3 participants | 3 participants | 3 participants | 3 participants | 16 participants | 3 participants | 52 participants |
| Sex: Female, Male Female | 3 Participants | 1 Participants | 1 Participants | 1 Participants | 15 Participants | 3 Participants | 3 Participants | 3 Participants | 3 Participants | 16 Participants | 3 Participants | 52 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk | EG007 affected / at risk | EG008 affected / at risk | EG009 affected / at risk | EG010 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 3 / 3 | 1 / 1 | 1 / 1 | 1 / 1 | 15 / 15 | 3 / 3 | 3 / 3 | 3 / 3 | 3 / 3 | 15 / 16 | 3 / 3 |
| serious Total, serious adverse events | 1 / 3 | 1 / 1 | 0 / 1 | 0 / 1 | 3 / 15 | 2 / 3 | 1 / 3 | 1 / 3 | 1 / 3 | 8 / 16 | 0 / 3 |
Outcome results
Primary
Maximum Tolerated Dose (MTD)
The highest dose level resulting in a DLT in ≤ 1 of 6 patients was declared the MTD.
Time frame: A minimum of 21 days after first dose of trastuzumab-MCC-DM1
Population: Safety evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Maximum Tolerated Dose (MTD) | 3.6 mg/kg |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Maximum Tolerated Dose (MTD) | 2.4 mg/kg |
Primary
Number of Patients With Dose Limiting Toxicities (DLTs)
DLT is defined as one of the following as per investigator related to study drug: * Grade ≥ 3 non-hematologic, non-hepatic major organ toxicity * Grade ≥ 3 cardiac toxicity, including cardiac troponin I elevation or any new segmental wall abnormality as determined by non-invasive cardiac imaging * Grade ≥ 4 thrombocytopenia * Grade ≥ 4 neutropenia (absolute neutrophil count \< 500/μ L) lasting \> 4 days or accompanied by fever * Grade ≥ 4 anemia * Grade ≥ 3 serum bilirubin, hepatic transaminase (alanine aminotransferase or aspartate aminotransferase), or alkaline phosphatase For patients with Grade 2 hepatic transaminase or alkaline phosphatase levels at baseline as a result of liver metastases or bone metastases, a hepatic transaminase or alkaline phosphatase level ≥ 10 times the upper limit of normal will be considered a DLT. * Weekly cohorts only: Toxicity preventing retreatment on Cycle 1, Day 8 or toxicity preventing re-treatment on Cycle 1, Days 15 and Day 22
Time frame: A minimum of 21 days after first dose of trastuzumab-MCC-DM1
Population: Safety Population included all treated patients
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Number of Patients With Dose Limiting Toxicities (DLTs) | 2 participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Number of Patients With Dose Limiting Toxicities (DLTs) | 0 participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Number of Patients With Dose Limiting Toxicities (DLTs) | 1 participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Number of Patients With Dose Limiting Toxicities (DLTs) | 2 participants |
Primary
Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment
The time frame for AEs is study treatment initiation until 30 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first. The time frame for SAEs is study treatment initiation until 90 days after last administration of study treatment or at the time of initiation of another anti-cancer therapy, which ever occurs first.
Time frame: Study treatment initiation until 30 or 90 days after last administration of study treatment
Population: Safety-evaluable population: All participants who received at least 1 dose of trastuzumab-MCC-DM1
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 100 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 0 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 0 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 0 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 0 percentage of participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 20 percentage of participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 93.3 percentage of participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 46.7 percentage of participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 100 percentage of participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 33.3 percentage of participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 50 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 81.3 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 87.5 percentage of participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 AE | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | At least 1 SAE | 0 percentage of participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs related to treatment | 100 percentage of participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Percentage of Participants With Adverse Events (AE), Serious Adverse Events (SAE), AEs With Grade >=3, and AEs Related To Treatment | AEs with Grade >=3 | 33.3 percentage of participants |
Primary
Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations
Time frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18
Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 9.63 μg/mL | Standard Deviation 1.73 |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 13.3 μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 20.3 μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 76.3 μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 76.2 μg/mL | Standard Deviation 19.1 |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 130 μg/mL | Standard Deviation 7.77 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 29.6 μg/mL | Standard Deviation 5.66 |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 34.3 μg/mL | Standard Deviation 4.81 |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 48.0 μg/mL | Standard Deviation 9.56 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 54.8 μg/mL | Standard Deviation 12.6 |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Pharmacokinetic (PK) Parameters After the First Dose: Maximum Observed Plasma Concentration Cmax for T-DM1 Concentrations | 78.1 μg/mL | Standard Deviation 33.9 |
Primary
PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations
Time frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18
Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 14.5 day • μg/mL | Standard Deviation 3.39 |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 24.5 day • μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 42.9 day • μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 330 day • μg/mL | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 300 day • μg/mL | Standard Deviation 65.8 |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 673 day • μg/mL | Standard Deviation 12.2 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 76.2 day • μg/mL | Standard Deviation 10.4 |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 130 day • μg/mL | Standard Deviation 39.7 |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 175 day • μg/mL | Standard Deviation 41 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 199 day • μg/mL | Standard Deviation 54.5 |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | PK Parameters After the First Dose: Area Under the Plasma Concentration-time Curve From 0 to Infinity (AUC[0-∞] for T-DM1 Concentrations | 212 day • μg/mL | Standard Deviation 39 |
Primary
PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations
Terminal phase elimination half-life (T1/2) is the time required for half of the drug to be eliminated from the plasma.
Time frame: 3-Week and Weekly Cohorts: Cycle 1 Day 1 Pre-dose 30 minutes and 4 hours after the end of infusion; Cycle 1 Day 2, 3, 4, 8 (Pre-dose 30 minutes after the end of infusion) 11, 15 (Pre-dose 30 minutes after the end of infusion) and 18
Population: Pharmacokinetic-evaluable patients were defined as patients who received at least one dose of T-DM1 with at least one post-dose concentration data point.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 1.3 day | Standard Deviation 0.2 |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 1.3 day | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 1.3 day | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 2.2 day | Standard Deviation 0 |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 3.1 day | Standard Deviation 0.7 |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 4.1 day | Standard Deviation 0.7 |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 2.3 day | Standard Deviation 0.6 |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 3.4 day | Standard Deviation 0.8 |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 3.1 day | Standard Deviation 0.3 |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 3.3 day | Standard Deviation 1.1 |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | PK Parameters After the First Dose: Terminal Half-life (t½) for T-DM1 Concentrations | 2.9 day | Standard Deviation 0.5 |
Secondary
Duration of Objective Response
Duration of objective response was defined as the time from the initial response to disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine.
Time frame: Baseline to the end of the study (up to 3 years 2 months)
Population: Efficacy population: All enrolled participants who received treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Duration of Objective Response | NA Months |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Duration of Objective Response | 10.5 Months |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Duration of Objective Response | NA Months |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Duration of Objective Response | 2.9 Months |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Duration of Objective Response | NA Months |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Duration of Objective Response | 5.6 Months |
Secondary
Percentage of Participants With an Objective Response
The occurrence of an objective response was determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST). An objective response was defined as a complete response or a partial response as determined on 2 consecutive occasions ≥ 4 weeks apart. A complete response was defined as the disappearance of all target lesions or the disappearance of all non-target lesions and normalization of tumor marker level. A partial response was defined as at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of the longest diameter of target lesions.
Time frame: Baseline to the end of the study (up to 3 years 2 months)
Population: Efficacy population: All enrolled participants who received treatment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 0 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 0 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 0 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 100 percentage of participants |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 26.7 percentage of participants |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Percentage of Participants With an Objective Response | 0 percentage of participants |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Percentage of Participants With an Objective Response | 100 percentage of participants |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Percentage of Participants With an Objective Response | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Percentage of Participants With an Objective Response | 66.7 percentage of participants |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Percentage of Participants With an Objective Response | 37.5 percentage of participants |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Percentage of Participants With an Objective Response | 0 percentage of participants |
Secondary
Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine
After the start of trastuzumab emtansine treatment, serum samples were collected every 3 weeks prior to trastuzumab emtansine dosing for detection of anti-therapeutic antibodies using a validated assay. A bridging antibody electrochemiluminescence assay (ECLA) was used to detect antibodies to trastuzumab emtansine. The assay utilized trastuzumab emtansine conjugated to biotin and a ruthenium label to form a complex with anti-trastuzumab emtansine antibodies. The antibody complex was captured by streptavidin-coated paramagnetic beads.
Time frame: Baseline to the end of the study (up to 3 years 2 months)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine | Pre-dose (Cycle 1, Day 1) | 0.0 percentage of participants |
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine | Any Visit after Dosing | 4.3 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine | Any Visit after Dosing | 0.0 percentage of participants |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Percentage of Participants With Anti-therapeutic Antibodies to Trastuzumab Emtansine | Pre-dose (Cycle 1, Day 1) | 3.7 percentage of participants |
Secondary
Progression-free Survival
Progression-free survival was defined as the time from first dose of trastuzumab emtansine to documented disease progression or death from any cause within 30 days of the last dose of trastuzumab emtansine, whichever occurred earlier. Progressive disease was defined as at least a 20% increase in the sum of the longest diameter of target lesions, taking as reference the smallest sum of the longest diameter of target lesions recorded since treatment started or the appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.
Time frame: Baseline to the end of the study (up to 3 years 2 months)
Population: Efficacy population: All enrolled participants who received treatment.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Trastuzumab-MCC-DM1 0.3 mg/kg Every 3 Weeks | Progression-free Survival | 2.7 Months |
| Trastuzumab-MCC-DM1 0.6 mg/kg Every 3 Weeks | Progression-free Survival | 1.7 Months |
| Trastuzumab-MCC-DM1 1.2 mg/kg Every 3 Weeks | Progression-free Survival | NA Months |
| Trastuzumab-MCC-DM1 2.4 mg/kg Every 3 Weeks | Progression-free Survival | NA Months |
| Trastuzumab-MCC-DM1 3.6 mg/kg Every 3 Weeks | Progression-free Survival | 10.4 Months |
| Trastuzumab-MCC-DM1 4.8 mg/kg Every 3 Weeks | Progression-free Survival | NA Months |
| Trastuzumab-MCC-DM1 1.2 mg/kg Weekly | Progression-free Survival | NA Months |
| Trastuzumab-MCC-DM1 1.6 mg/kg Weekly | Progression-free Survival | 4.5 Months |
| Trastuzumab-MCC-DM1 2.0 mg/kg Weekly | Progression-free Survival | NA Months |
| Trastuzumab-MCC-DM1 2.4 mg/kg Weekly | Progression-free Survival | 5.7 Months |
| Trastuzumab-MCC-DM1 2.9 mg/kg Weekly | Progression-free Survival | 2.0 Months |