Breast Neoplasms
Conditions
Keywords
HER2, PF-06804103, ADC, breast cancer, neoplasms, solid tumors, human epidermal growth receptor 2
Brief summary
The study will evaluate the safety, pharmacokinetics and pharmacodynamics of increasing doses of PF-06804103 in patients with HER2 positive and negative breast and gastric cancer (HER2 positive only and gastric were studied in Part 1A only). The study will expand to look at selected doses in patients with HER2 positive and negative breast cancer.
Interventions
DRUGPF-06804103
Dose Escalation Part - 1A Dose Expansion Part - 2A
DRUGPF-06804103 + Palbociclib +Letrozole
Dose Escalation - Part 1B Dose Expansion - Part 2B
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* HER2 positive breast cancer or gastric cancer that is resistant to standard therapy or for which no standard therapy is available (Part 1A only) * HER2 positive and negative breast cancer (Part 2A) * HER2 negative breast cancer (Part 1B & Part 2B) * Performance status of 0 or 1 * Adequate bone marrow, kidney and liver function
Exclusion criteria
* Known CNS disease including, but not limited to, metastases * History of exposure to certain cumulative doses of anthracyclines * Grade 3 or higher hypersensitivity reaction to prior receipt of any antibody therapy * Active and clinically significant bacterial, fungal, or viral infection * Abnormal cardiac function defined by a LVEF \<50% by ECHO or MUGA * Patients with previous history or active interstitial lung disease or pulmonary fibrosis, or a history of other clinically significant lung diseases
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | First cycle, Day 1 up to Day 21 | A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose). (1) Hematologic: Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>＝3 neutropenic infection; Grade \>＝3 thrombocytopenia with bleeding; thrombocytopenia; (2) Non-hematologic: Grade \>=3 toxicities that were considered clinically significant; delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting treatment related toxicities; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event. |
| Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B | First Cycle, Day 1 up to Day 28 | A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 28 days of first dose). (1) Hematologic: including a delay greater than 1 week in administration of the next scheduled dose of study treatment due to persistent treatment-related toxicities; Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; thrombocytopenia. (2) Non-hematologic: including Grade \>=3 toxicities that are considered clinically significant; Grade 3 QTc prolongation despite correction of reversible causes; delayed by \>2 week in receiving the next scheduled dose of any study treatment due to persisting treatment-related toxicities; inability to administer at least 80% of the planned palbociclib or letrozole or 100% of the planned PF-06804103 doses during Cycle 1 due to toxicity related to the study treatment; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event. |
| Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as those with initial onset or increasing in severity after the first dose of study medication. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator. |
| Number of Participants With Laboratory Abnormalities-Hematology | From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B) | Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: anemia, INR increased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased. |
| Number of Participants With Laboratory Abnormalities-Chemistries | From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B) | Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, hyperglycemia, hypermagnesemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased. |
| Number of Participants With Laboratory Abnormalities-Urinalysis | From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B) | Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above. |
| Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B | Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position. |
| Percentage of Participants With Objective Response in Part 2 | Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks) | Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Duration of Response (DR) in Part 2 | Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks) | Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Progression-Free Survival (PFS) in Part 2 | Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks) | Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Time to Tumor Progression (TTP) in Part 2 | Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks) | Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Observed Accumulation Ratio (Rac) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Cmax of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Cmax is maximum observed serum concentration. Cmax for PF-06804103 total antibody was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Total antibody means PF-06804103 with or without PF-06380101 conjugated. Both the antibody and small molecule components of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK. |
| t1/2 of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| AUCinf of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B | AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| AUCtau of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B | Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| CL of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 total antibody was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Percentage of Participants With Objective Response in Part 1 | Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B) | Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. |
| Rac of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Cmax of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Cmax is maximum observed serum concentration. Cmax for PF-06380101 unconjugated payload was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Small molecule components (PF-06380101) of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK. |
| Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Tmax is the time for Cmax. Tmax for PF-06380101 unconjugated payload was observed directly from data as time of first occurrence.Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| t1/2 of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| AUCinf of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B | AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| AUCtau of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B | Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Rac of PF-06380101 Unconjugated Payload | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B | Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Vss of PF-06804103 Total Antibody | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Duration of Response (DR) in Part 1 | Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B) | Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Progression-Free Survival (PFS) in Part 1 | Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B) | Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Time to Tumor Progression (TTP) in Part 1 | Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B) | Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions. |
| Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B) | To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06804103. |
| Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | Baseline | Tumor tissues from archived tissue biopsy were analyzed for HER2 mutations. |
| Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Cmax is maximum observed serum concentration. Cmax for PF-06804103 ADC was observed directly from data. Part 2A used a sparse pharmacokinetic (PK) sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B | AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B | Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 ADC was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
| Clearance (CL) of PF-06804103 ADC | Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B | Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 ADC was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. |
Countries
Australia, Italy, Russia, South Korea, Spain, United States
Participant flow
Recruitment details
Part A (PF-06804103 monotherapy) included Part 1A (dose escalation part) and Part 2A (dose expansion part). Part B (PF-06804103 plus palbociclib and letrozole combination therapy) included Part 1B (dose escalation part).
Pre-assignment details
In Part 1A, 47 participants were treated at dose levels of PF-06804103 0.15, 0.5, 1.2, 2.0, 3.0, 4.0 and 5.0 mg/kg. In Part 2A, 46 participants were treated at dose levels of PF-06804103 3.0 and 4.0 mg/kg. In Part 1B, 2 participants received PF-06804103 2.0 mg/kg in combination with standard of care (SOC) doses of palbociclib and letrozole. Participants were unique in each part.
Participants by arm
| Arm | Count |
|---|---|
| PART 1A PF-06804103 0.15 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 0.15 mg/kg on Day 1 of each 21-day cycle as an intravenous (IV) infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. HER2 = Human Epidermal Growth Factor Receptor 2; BC = breast cancer; GC = gastric and gastroesophageal cancer. | 2 |
| PART 1A PF-06804103 0.5 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 0.5 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 2 |
| PART 1A PF-06804103 1.2 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 1.2 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 2 |
| PART 1A PF-06804103 2.0 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 2.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 4 |
| PART 1A PF-06804103 3.0 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 3.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 16 |
| PART 1A PF-06804103 4.0 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 4.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 15 |
| PART 1A PF-06804103 5.0 mg/kg Participants with HER2-positive BC or HER2-positive GC received PF-06804103 at 5.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 1A was approximately 89.3 weeks. | 6 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC Participants with HER2-positive BC in third line (3L) setting received PF-06804103 at 3.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 2A was approximately 49.4 weeks. | 5 |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC Participants with HER2-positive BC in 3L setting received PF-06804103 at 4.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 2A was approximately 49.4 weeks. | 14 |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC Participants with HR-positive HER2 IHC
1+ or IHC 2+/ISH- BC in second line (2L) setting received PF-06804103 at 3.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 2A was approximately 49.4 weeks. HR = hormone receptor; IHC = immunohistochemistry; ISH = in-situ hybridization. | 12 |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC Participants with HR-positive HER2 IHC
1+ or IHC 2+/ISH- BC in 2L setting received PF-06804103 at 4.0 mg/kg on Day 1 of each 21-day cycle as an IV infusion. The maximum duration of treatment for Part 2A was approximately 49.4 weeks. | 15 |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC Postmenopausal participants with HR-positive HER2 IHC 1+ or IHC 2+/ISH- BC received PF-06804103 at 2.0 mg/kg once every 14 days in a 28-day cycle as an IV infusion. The maximum duration of treatment for Part 1B was approximately 53.7 weeks. | 2 |
| Total | 95 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 | FG007 | FG008 | FG009 | FG010 | FG011 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Death | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
| Overall Study | Lost to Follow-up | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 2 | 0 | 0 |
| Overall Study | Other | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Overall Study | Study Terminated By Sponsor | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 |
| Overall Study | Withdrawal by Subject | 0 | 0 | 0 | 0 | 5 | 3 | 1 | 0 | 6 | 0 | 3 | 1 |
Baseline characteristics
| Characteristic | PART 1A PF-06804103 5.0 mg/kg | PART 2A PF-06804103 3.0 mg/kg HER2+ BC | PART 2A PF-06804103 4.0 mg/kg HER2+ BC | PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Total | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1A PF-06804103 0.15 mg/kg | PART 1A PF-06804103 0.5 mg/kg | PART 1A PF-06804103 1.2 mg/kg | PART 1A PF-06804103 2.0 mg/kg | PART 1A PF-06804103 3.0 mg/kg | PART 1A PF-06804103 4.0 mg/kg |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | 55.5 Years STANDARD_DEVIATION 11.33 | 50.8 Years STANDARD_DEVIATION 6.57 | 50.0 Years STANDARD_DEVIATION 8.68 | 58.3 Years STANDARD_DEVIATION 10.36 | 54.5 Years STANDARD_DEVIATION 10.74 | 53.0 Years STANDARD_DEVIATION 9.9 | 53.8 Years STANDARD_DEVIATION 11.67 | 49.0 Years STANDARD_DEVIATION 19.8 | 65.5 Years STANDARD_DEVIATION 0.71 | 58.0 Years STANDARD_DEVIATION 11.31 | 67.0 Years STANDARD_DEVIATION 4.69 | 54.5 Years STANDARD_DEVIATION 11.06 | 53.1 Years STANDARD_DEVIATION 11.7 |
| Age, Customized <18 | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Customized 18-44 | 1 Participants | 1 Participants | 5 Participants | 1 Participants | 21 Participants | 0 Participants | 5 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 3 Participants | 4 Participants |
| Age, Customized 45-64 | 4 Participants | 4 Participants | 8 Participants | 7 Participants | 53 Participants | 2 Participants | 7 Participants | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 10 Participants | 8 Participants |
| Age, Customized >=65 | 1 Participants | 0 Participants | 1 Participants | 4 Participants | 21 Participants | 0 Participants | 3 Participants | 0 Participants | 2 Participants | 1 Participants | 3 Participants | 3 Participants | 3 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 6 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants | 5 Participants | 14 Participants | 11 Participants | 88 Participants | 2 Participants | 13 Participants | 2 Participants | 1 Participants | 2 Participants | 4 Participants | 14 Participants | 14 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 1 Participants | 9 Participants | 1 Participants | 28 Participants | 2 Participants | 3 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 4 Participants | 5 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 4 Participants | 4 Participants | 11 Participants | 62 Participants | 0 Participants | 12 Participants | 1 Participants | 1 Participants | 2 Participants | 2 Participants | 10 Participants | 10 Participants |
| Sex: Female, Male Female | 4 Participants | 5 Participants | 14 Participants | 12 Participants | 77 Participants | 2 Participants | 15 Participants | 0 Participants | 1 Participants | 1 Participants | 2 Participants | 11 Participants | 10 Participants |
| Sex: Female, Male Male | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 18 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants | 1 Participants | 2 Participants | 5 Participants | 5 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 | EG011 affected / at risk |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 1 / 2 | 0 / 2 | 0 / 2 | 1 / 4 | 0 / 16 | 1 / 15 | 1 / 6 | 0 / 5 | 0 / 14 | 3 / 12 | 1 / 15 | 0 / 2 |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 2 / 2 | 4 / 4 | 16 / 16 | 15 / 15 | 6 / 6 | 5 / 5 | 14 / 14 | 11 / 12 | 15 / 15 | 2 / 2 |
| serious Total, serious adverse events | 1 / 2 | 0 / 2 | 0 / 2 | 1 / 4 | 7 / 16 | 5 / 15 | 4 / 6 | 2 / 5 | 6 / 14 | 5 / 12 | 7 / 15 | 0 / 2 |
Outcome results
Primary
Duration of Response (DR) in Part 2
Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
Population: Participants received at least 1 dose of study treatment with adequate baseline assessment and at least 1 determinate post baseline assessment, disease progression, or death before the first tumor assessment. DR was only for the subset participants with an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Duration of Response (DR) in Part 2 | NA Month |
| PART 1A PF-06804103 0.5 mg/kg | Duration of Response (DR) in Part 2 | 2.9 Month |
| PART 1A PF-06804103 1.2 mg/kg | Duration of Response (DR) in Part 2 | 4 Month |
| PART 1A PF-06804103 2.0 mg/kg | Duration of Response (DR) in Part 2 | NA Month |
Primary
Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs
An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) was an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment-emergent AEs (TEAEs) were defined as those with initial onset or increasing in severity after the first dose of study medication. A treatment-related AE was any untoward medical occurrence attributed to the study drug in a participant who received study drug. Relatedness to study drug was assessed by the investigator.
Time frame: From the first dose of study treatment up to a minimum of 28 calendar days after the last dose of study treatment (maximum duration between first and last dose: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
Population: All enrolled participants who received at least one dose of study treatment.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 2 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 1 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 1 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 1 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 2 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 2 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 1 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 4 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 4 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 16 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 15 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 3 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 7 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 5 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 15 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 15 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 2 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 4 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 6 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 6 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 5 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 5 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 5 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 14 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 14 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 6 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 5 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 12 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 10 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 15 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 7 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 15 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 5 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality SAEs | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with all-causality TEAEs | 2 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related TEAEs | 2 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With All-Causality Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event (SAEs), Treatment-Related TEAEs and SAEs | Number of Participants with treatment-related SAEs | 0 Participants |
Primary
Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A
A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 21 days of first dose). (1) Hematologic: Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>＝3 neutropenic infection; Grade \>＝3 thrombocytopenia with bleeding; thrombocytopenia; (2) Non-hematologic: Grade \>=3 toxicities that were considered clinically significant; delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting treatment related toxicities; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.
Time frame: First cycle, Day 1 up to Day 21
Population: Participants enrolled in Part 1A who received at least 1 dose of study treatment and who did not have major treatment deviations during first cycle.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 2 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 2 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities-Chemistries
Participants who experienced chemistry laboratory test abnormalities were summarized according to worst toxicity grade observed for each chemistry laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with chemistry laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: alanine aminotransferase (ALT) increased, alkaline phosphatase (ALP) increased, aspartate aminotransferase (AST) increased, hyperglycemia, hypermagnesemia, hypocalcemia, hypokalemia, hyponatremia, hypophosphatemia, lipase increased, serum amylase increased.
Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
Population: Participants who had at least one on-treatment assessment for the corresponding lab parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 1 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 1 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 2 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 2 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 3 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Lipase increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Serum amylase increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALP increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypokalemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypermagnesemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | AST increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | ALT increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypophosphatemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hypocalcemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyponatremia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Chemistries | Hyperglycemia | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities-Hematology
Participants who experienced hematology laboratory test abnormalities were summarized according to worst toxicity grade observed for each hematology laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with hematology laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above, including the following parameters: anemia, INR increased, lymphocyte count decreased, neutrophil count decreased, white blood cell decreased.
Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
Population: Participants who had at least one on-treatment assessment for the corresponding lab parameter.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 1 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 2 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 2 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 1 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 3 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 3 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Hematology | Anemia | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Hematology | Lymphocyte count decreased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Hematology | White blood cell decreased | 1 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Hematology | INR increased | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Hematology | Neutrophil count decreased | 0 Participants |
Primary
Number of Participants With Laboratory Abnormalities-Urinalysis
Participants who experienced urinalysis laboratory test abnormalities were summarized according to worst toxicity grade observed for each urinalysis laboratory test. Laboratory abnormalities were graded by NCI CTCAE version 4.03 (Grade 0: no change from normal or reference range; Grade 1: mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequences, urgent intervention indicated). This outcome measure calculated the number of participants with urinalysis laboratory abnormalities that were shifted from \<=Grade 2 at baseline to Grade 3 or above.
Time frame: From baseline to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
Population: Participants who had at least one on-treatment assessment for the corresponding lab parameter.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Laboratory Abnormalities-Urinalysis | 0 Participants |
Primary
Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position.
Time frame: From baseline up to follow up (at least 28 days and no more than 35 days after discontinuation of treatment), maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B
Population: Participants who were evaluated against criteria.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 1 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 1 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 2 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 2 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 2 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 2 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 2 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 4 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 2 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 4 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 2 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 3 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 3 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 3 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 9 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 5 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 7 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 6 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 6 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 2 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 1 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 3 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 3 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 3 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 1 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 3 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 4 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 5 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 4 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 1 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | SBP value <90 mmHg | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in DBP ≥20 mmHg | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in DBP ≥20 mmHg | 1 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Decrease in SBP ≥30 mmHg | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Increase in SBP ≥30 mmHg | 1 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | Pulse rate >120 beats per minute (bpm) | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Vital Signs Data Meeting Pre-Defined Criteria | DBP value <50 mmHg | 0 Participants |
Primary
Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B
A DLT was any of the following adverse events(AEs) in the first cycle of treatment (within 28 days of first dose). (1) Hematologic: including a delay greater than 1 week in administration of the next scheduled dose of study treatment due to persistent treatment-related toxicities; Grade 4 neutropenia lasting \>7 days; febrile neutropenia; Grade \>=3 neutropenic infection; Grade \>=3 thrombocytopenia with bleeding; thrombocytopenia. (2) Non-hematologic: including Grade \>=3 toxicities that are considered clinically significant; Grade 3 QTc prolongation despite correction of reversible causes; delayed by \>2 week in receiving the next scheduled dose of any study treatment due to persisting treatment-related toxicities; inability to administer at least 80% of the planned palbociclib or letrozole or 100% of the planned PF-06804103 doses during Cycle 1 due to toxicity related to the study treatment; concurrent AST or ALT \>3x ULN and total bilirubin \>2x ULN; any Grade 5 event.
Time frame: First Cycle, Day 1 up to Day 28
Population: Participants enrolled in Part 1B who received at least 1 dose of study treatment and who did not have major treatment deviations during first cycle.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B | 0 Participants |
Primary
Percentage of Participants With Objective Response in Part 2
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
Population: Participants received at least 1 dose of study treatment with adequate baseline assessment and at least 1 determinate post baseline assessment, disease progression, or death before the first tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Percentage of Participants With Objective Response in Part 2 | 25.0 Percentage of participants |
| PART 1A PF-06804103 0.5 mg/kg | Percentage of Participants With Objective Response in Part 2 | 45.5 Percentage of participants |
| PART 1A PF-06804103 1.2 mg/kg | Percentage of Participants With Objective Response in Part 2 | 10.0 Percentage of participants |
| PART 1A PF-06804103 2.0 mg/kg | Percentage of Participants With Objective Response in Part 2 | 27.3 Percentage of participants |
Primary
Progression-Free Survival (PFS) in Part 2
Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 49.4 weeks)
Population: All enrolled participants in part 2A.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Progression-Free Survival (PFS) in Part 2 | NA Month |
| PART 1A PF-06804103 0.5 mg/kg | Progression-Free Survival (PFS) in Part 2 | 5.5 Month |
| PART 1A PF-06804103 1.2 mg/kg | Progression-Free Survival (PFS) in Part 2 | 1.3 Month |
| PART 1A PF-06804103 2.0 mg/kg | Progression-Free Survival (PFS) in Part 2 | 5.6 Month |
Primary
Time to Tumor Progression (TTP) in Part 2
Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks from the start of treatment until disease progression, death, or withdrawal from treatment (maximum treatment duration: 49.4 weeks)
Population: All enrolled participants in part 2A.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Time to Tumor Progression (TTP) in Part 2 | NA Month |
| PART 1A PF-06804103 0.5 mg/kg | Time to Tumor Progression (TTP) in Part 2 | 5.5 Month |
| PART 1A PF-06804103 1.2 mg/kg | Time to Tumor Progression (TTP) in Part 2 | 1.3 Month |
| PART 1A PF-06804103 2.0 mg/kg | Time to Tumor Progression (TTP) in Part 2 | 5.6 Month |
Secondary
Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC
Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 ADC was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | NA µg*hr/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | NA µg*hr/mL | — |
| PART 1A PF-06804103 2.0 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | NA µg*hr/mL | — |
| PART 1A PF-06804103 3.0 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | 7504 µg*hr/mL | Geometric Coefficient of Variation 28 |
| PART 1A PF-06804103 4.0 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | 10730 µg*hr/mL | Geometric Coefficient of Variation 33 |
| PART 1A PF-06804103 5.0 mg/kg | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | 11990 µg*hr/mL | Geometric Coefficient of Variation 23 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | NA µg*hr/mL | — |
Secondary
Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | NA microgram*hour/milliliter (µg*hr/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | NA microgram*hour/milliliter (µg*hr/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | NA microgram*hour/milliliter (µg*hr/mL) | — |
| PART 1A PF-06804103 2.0 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | 5120 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 11 |
| PART 1A PF-06804103 3.0 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | 9498 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 32 |
| PART 1A PF-06804103 4.0 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | 12940 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 31 |
| PART 1A PF-06804103 5.0 mg/kg | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | 16550 microgram*hour/milliliter (µg*hr/mL) | Geometric Coefficient of Variation 38 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | NA microgram*hour/milliliter (µg*hr/mL) | — |
Secondary
AUCinf of PF-06380101 Unconjugated Payload
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | NA nanogram*hour/milliliter (ng*hr/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | NA nanogram*hour/milliliter (ng*hr/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | NA nanogram*hour/milliliter (ng*hr/mL) | — |
| PART 1A PF-06804103 2.0 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | 465.8 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 45 |
| PART 1A PF-06804103 3.0 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | 945.4 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 51 |
| PART 1A PF-06804103 4.0 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | 1256 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 43 |
| PART 1A PF-06804103 5.0 mg/kg | AUCinf of PF-06380101 Unconjugated Payload | 1824 nanogram*hour/milliliter (ng*hr/mL) | Geometric Coefficient of Variation 83 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | AUCinf of PF-06380101 Unconjugated Payload | NA nanogram*hour/milliliter (ng*hr/mL) | — |
Secondary
AUCinf of PF-06804103 Total Antibody
AUCinf is the area under the serum concentration-time profile from time zero extrapolated to infinite time. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | AUCinf of PF-06804103 Total Antibody | NA µg*hr/mL | — |
| PART 1A PF-06804103 0.5 mg/kg | AUCinf of PF-06804103 Total Antibody | NA µg*hr/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | AUCinf of PF-06804103 Total Antibody | NA µg*hr/mL | — |
| PART 1A PF-06804103 2.0 mg/kg | AUCinf of PF-06804103 Total Antibody | 6868 µg*hr/mL | Geometric Coefficient of Variation 62 |
| PART 1A PF-06804103 3.0 mg/kg | AUCinf of PF-06804103 Total Antibody | 10770 µg*hr/mL | Geometric Coefficient of Variation 53 |
| PART 1A PF-06804103 4.0 mg/kg | AUCinf of PF-06804103 Total Antibody | 15360 µg*hr/mL | Geometric Coefficient of Variation 58 |
| PART 1A PF-06804103 5.0 mg/kg | AUCinf of PF-06804103 Total Antibody | 18010 µg*hr/mL | Geometric Coefficient of Variation 38 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | AUCinf of PF-06804103 Total Antibody | NA µg*hr/mL | — |
Secondary
AUCtau of PF-06380101 Unconjugated Payload
Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | NA ng*hr/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | NA ng*hr/mL | — |
| PART 1A PF-06804103 2.0 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | 478.0 ng*hr/mL | Geometric Coefficient of Variation 124 |
| PART 1A PF-06804103 3.0 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | 556.5 ng*hr/mL | Geometric Coefficient of Variation 45 |
| PART 1A PF-06804103 4.0 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | 780.8 ng*hr/mL | Geometric Coefficient of Variation 56 |
| PART 1A PF-06804103 5.0 mg/kg | AUCtau of PF-06380101 Unconjugated Payload | 1136 ng*hr/mL | Geometric Coefficient of Variation 19 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | AUCtau of PF-06380101 Unconjugated Payload | NA ng*hr/mL | — |
Secondary
AUCtau of PF-06804103 Total Antibody
Tau refers to the dosing interval and it equals to 504 hours for Part 1A and 336 hours for Part 1B. AUCtau is the area under the concentration-time profile from time zero to time tau. AUCtau for PF-06804103 total antibody was determined using linear/log trapezoidal method. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | AUCtau of PF-06804103 Total Antibody | NA µg*hr/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | AUCtau of PF-06804103 Total Antibody | NA µg*hr/mL | — |
| PART 1A PF-06804103 2.0 mg/kg | AUCtau of PF-06804103 Total Antibody | 4826 µg*hr/mL | Geometric Coefficient of Variation 18 |
| PART 1A PF-06804103 3.0 mg/kg | AUCtau of PF-06804103 Total Antibody | 8231 µg*hr/mL | Geometric Coefficient of Variation 30 |
| PART 1A PF-06804103 4.0 mg/kg | AUCtau of PF-06804103 Total Antibody | 10980 µg*hr/mL | Geometric Coefficient of Variation 32 |
| PART 1A PF-06804103 5.0 mg/kg | AUCtau of PF-06804103 Total Antibody | 12870 µg*hr/mL | Geometric Coefficient of Variation 21 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | AUCtau of PF-06804103 Total Antibody | NA µg*hr/mL | — |
Secondary
Clearance (CL) of PF-06804103 ADC
Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 ADC was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 0.5 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 0.5 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 1.2 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 1.2 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 2.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | 0.02073 Liter/hour (L/hr) | Geometric Coefficient of Variation 32 |
| PART 1A PF-06804103 2.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | NA Liter/hour (L/hr) | — |
| PART 1A PF-06804103 3.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | 0.02069 Liter/hour (L/hr) | Geometric Coefficient of Variation 28 |
| PART 1A PF-06804103 3.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | 0.01970 Liter/hour (L/hr) | Geometric Coefficient of Variation 27 |
| PART 1A PF-06804103 4.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | 0.01884 Liter/hour (L/hr) | Geometric Coefficient of Variation 24 |
| PART 1A PF-06804103 4.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | 0.01731 Liter/hour (L/hr) | Geometric Coefficient of Variation 27 |
| PART 1A PF-06804103 5.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 1 | 0.01975 Liter/hour (L/hr) | Geometric Coefficient of Variation 40 |
| PART 1A PF-06804103 5.0 mg/kg | Clearance (CL) of PF-06804103 ADC | Cycle 4 | 0.01971 Liter/hour (L/hr) | Geometric Coefficient of Variation 49 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Clearance (CL) of PF-06804103 ADC | Cycle 4 | NA Liter/hour (L/hr) | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Clearance (CL) of PF-06804103 ADC | Cycle 1 | NA Liter/hour (L/hr) | — |
Secondary
CL of PF-06804103 Total Antibody
Clearance (CL) is a quantitative measure of the rate at which a drug substance is removed from the body. Clearance for PF-06804103 total antibody was calculated as dose/AUCinf for single dose and dose/AUCtau for multiple dose, where AUCinf was the area under the serum concentration-time profile from time zero extrapolated to infinite time and AUCtau was the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | NA L/hr | — |
| PART 1A PF-06804103 0.5 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | NA L/hr | — |
| PART 1A PF-06804103 0.5 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | NA L/hr | — |
| PART 1A PF-06804103 1.2 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | NA L/hr | — |
| PART 1A PF-06804103 1.2 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | NA L/hr | — |
| PART 1A PF-06804103 2.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | 0.01544 L/hr | Geometric Coefficient of Variation 103 |
| PART 1A PF-06804103 2.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | 0.01777 L/hr | Geometric Coefficient of Variation 15 |
| PART 1A PF-06804103 3.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | 0.01890 L/hr | Geometric Coefficient of Variation 29 |
| PART 1A PF-06804103 3.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | 0.01737 L/hr | Geometric Coefficient of Variation 47 |
| PART 1A PF-06804103 4.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | 0.01587 L/hr | Geometric Coefficient of Variation 46 |
| PART 1A PF-06804103 4.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | 0.01693 L/hr | Geometric Coefficient of Variation 27 |
| PART 1A PF-06804103 5.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 1 | 0.01899 L/hr | Geometric Coefficient of Variation 37 |
| PART 1A PF-06804103 5.0 mg/kg | CL of PF-06804103 Total Antibody | Cycle 4 | 0.02023 L/hr | Geometric Coefficient of Variation 37 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | CL of PF-06804103 Total Antibody | Cycle 1 | NA L/hr | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | CL of PF-06804103 Total Antibody | Cycle 4 | NA L/hr | — |
Secondary
Cmax of PF-06380101 Unconjugated Payload
Cmax is maximum observed serum concentration. Cmax for PF-06380101 unconjugated payload was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Small molecule components (PF-06380101) of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | NA nanogram/milliliter (ng/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | NA nanogram/milliliter (ng/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | NA nanogram/milliliter (ng/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | NA nanogram/milliliter (ng/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | NA nanogram/milliliter (ng/mL) | — |
| PART 1A PF-06804103 2.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | 1.706 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 73 |
| PART 1A PF-06804103 2.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | 2.254 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 108 |
| PART 1A PF-06804103 3.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | 3.180 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 41 |
| PART 1A PF-06804103 3.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | 2.185 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 59 |
| PART 1A PF-06804103 4.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | 4.219 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 43 |
| PART 1A PF-06804103 4.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | 3.094 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 78 |
| PART 1A PF-06804103 5.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | 4.790 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 15 |
| PART 1A PF-06804103 5.0 mg/kg | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | 6.916 nanogram/milliliter (ng/mL) | Geometric Coefficient of Variation 67 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Cmax of PF-06380101 Unconjugated Payload | Cycle 1 | NA nanogram/milliliter (ng/mL) | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Cmax of PF-06380101 Unconjugated Payload | Cycle 4 | NA nanogram/milliliter (ng/mL) | — |
Secondary
Cmax of PF-06804103 Total Antibody
Cmax is maximum observed serum concentration. Cmax for PF-06804103 total antibody was observed directly from data. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure. Total antibody means PF-06804103 with or without PF-06380101 conjugated. Both the antibody and small molecule components of the ADC are critical to its activity, requiring assays suited to measuring these disparate components. Each analyte provides unique information regarding ADC behavior in vivo and, singly or in combination, facilitates understanding of ADC PK.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | NA µg/mL | — |
| PART 1A PF-06804103 0.5 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | NA µg/mL | — |
| PART 1A PF-06804103 0.5 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | NA µg/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | NA µg/mL | — |
| PART 1A PF-06804103 1.2 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | NA µg/mL | — |
| PART 1A PF-06804103 2.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | 44.02 µg/mL | Geometric Coefficient of Variation 10 |
| PART 1A PF-06804103 2.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | 46.77 µg/mL | Geometric Coefficient of Variation 24 |
| PART 1A PF-06804103 3.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | 78.17 µg/mL | Geometric Coefficient of Variation 34 |
| PART 1A PF-06804103 3.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | 59.96 µg/mL | Geometric Coefficient of Variation 26 |
| PART 1A PF-06804103 4.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | 77.53 µg/mL | Geometric Coefficient of Variation 21 |
| PART 1A PF-06804103 4.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | 89.67 µg/mL | Geometric Coefficient of Variation 31 |
| PART 1A PF-06804103 5.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 1 | 117.7 µg/mL | Geometric Coefficient of Variation 19 |
| PART 1A PF-06804103 5.0 mg/kg | Cmax of PF-06804103 Total Antibody | Cycle 4 | 88.54 µg/mL | Geometric Coefficient of Variation 9 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Cmax of PF-06804103 Total Antibody | Cycle 1 | NA µg/mL | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Cmax of PF-06804103 Total Antibody | Cycle 4 | NA µg/mL | — |
Secondary
Duration of Response (DR) in Part 1
Duration of response (DR) was the time from first documentation of PR or CR to date of first documentation of progressive disease (PD) or death due to any cause. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
Population: Participants received at least 1 dose of study treatment with adequate baseline assessment and at least 1 determinate post baseline assessment, disease progression, or death before the first tumor assessment. DR was only for the subset participants with an objective response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 1.2 mg/kg | Duration of Response (DR) in Part 1 | 4.2 Month |
| PART 1A PF-06804103 3.0 mg/kg | Duration of Response (DR) in Part 1 | 15.5 Month |
| PART 1A PF-06804103 4.0 mg/kg | Duration of Response (DR) in Part 1 | 7.3 Month |
| PART 1A PF-06804103 5.0 mg/kg | Duration of Response (DR) in Part 1 | NA Month |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Duration of Response (DR) in Part 1 | NA Month |
Secondary
Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC)
Cmax is maximum observed serum concentration. Cmax for PF-06804103 ADC was observed directly from data. Part 2A used a sparse pharmacokinetic (PK) sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | NA microgram/milliliter (µg/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | NA microgram/milliliter (µg/mL) | — |
| PART 1A PF-06804103 0.5 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | NA microgram/milliliter (µg/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | NA microgram/milliliter (µg/mL) | — |
| PART 1A PF-06804103 1.2 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | NA microgram/milliliter (µg/mL) | — |
| PART 1A PF-06804103 2.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | 36.97 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 24 |
| PART 1A PF-06804103 2.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | 43.00 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 15 |
| PART 1A PF-06804103 3.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | 71.24 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| PART 1A PF-06804103 3.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | 53.29 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 29 |
| PART 1A PF-06804103 4.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | 76.52 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 24 |
| PART 1A PF-06804103 4.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | 78.91 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 21 |
| PART 1A PF-06804103 5.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | 82.13 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 7 |
| PART 1A PF-06804103 5.0 mg/kg | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | 103.1 microgram/milliliter (µg/mL) | Geometric Coefficient of Variation 28 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 1 | NA microgram/milliliter (µg/mL) | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Maximum Observed Concentration (Cmax) of PF-06804103 Antibody-Drug Conjugate (ADC) | Cycle 4 | NA microgram/milliliter (µg/mL) | — |
Secondary
Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103
To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06804103.
Time frame: Prior to the start of treatment on Day 1 of Cycle 1 up to end of treatment (maximum treatment duration: 89.3 weeks for Part 1A, 49.4 weeks for Part 2A, 53.7 weeks for Part 1B)
Population: All enrolled participants who received at least one dose of study treatment and had at least 1 ADA sample collected.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 1 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 1 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 2 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 2 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 2 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 4 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 2 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 5 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with ADA | 0 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With Anti-Drug Antibodies (ADA) and Neutralizing Antibody (NAb) Against PF-06804103 | Participants with NAb | 0 Participants |
Secondary
Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis
Tumor tissues from archived tissue biopsy were analyzed for HER2 mutations.
Time frame: Baseline
Population: All enrolled participants with at least 1 of the biomarkers evaluated at pre- and/or post-dose.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 2 Participants |
| PART 1A PF-06804103 0.5 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 2 Participants |
| PART 1A PF-06804103 1.2 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 1 Participants |
| PART 1A PF-06804103 2.0 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 3 Participants |
| PART 1A PF-06804103 3.0 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 10 Participants |
| PART 1A PF-06804103 4.0 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 13 Participants |
| PART 1A PF-06804103 5.0 mg/kg | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 6 Participants |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 5 Participants |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 14 Participants |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 4 Participants |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 1 Participants |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 0 Participants |
Secondary
Observed Accumulation Ratio (Rac) of PF-06804103 ADC
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | NA Ratio | — |
| PART 1A PF-06804103 1.2 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | NA Ratio | — |
| PART 1A PF-06804103 2.0 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | NA Ratio | — |
| PART 1A PF-06804103 3.0 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | 1.007 Ratio | Geometric Coefficient of Variation 20 |
| PART 1A PF-06804103 4.0 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | 1.164 Ratio | Geometric Coefficient of Variation 22 |
| PART 1A PF-06804103 5.0 mg/kg | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | 1.114 Ratio | Geometric Coefficient of Variation 15 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Observed Accumulation Ratio (Rac) of PF-06804103 ADC | NA Ratio | — |
Secondary
Percentage of Participants With Objective Response in Part 1
Percentage of participants with objective response based on assessment of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. CR was defined as complete disappearance of all target lesions and non-target disease, with the exception of nodal disease. All nodes, both target and non-target, must decrease to normal (short axis \<10 mm). No new lesions. PR was defined as \>=30% decrease under baseline of the sum of diameters of all target lesions. The short axis was used in the sum for target nodes, while the longest diameter was used in the sum for all other target lesions. No unequivocal progression of non-target disease. No new lesions.
Time frame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
Population: Participants received at least 1 dose of study treatment with adequate baseline assessment and at least 1 determinate post baseline assessment, disease progression, or death before the first tumor assessment.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Percentage of Participants With Objective Response in Part 1 | 16.7 Percentage of participants |
| PART 1A PF-06804103 0.5 mg/kg | Percentage of Participants With Objective Response in Part 1 | 0 Percentage of participants |
| PART 1A PF-06804103 1.2 mg/kg | Percentage of Participants With Objective Response in Part 1 | 21.4 Percentage of participants |
| PART 1A PF-06804103 2.0 mg/kg | Percentage of Participants With Objective Response in Part 1 | 42.9 Percentage of participants |
| PART 1A PF-06804103 3.0 mg/kg | Percentage of Participants With Objective Response in Part 1 | 60.0 Percentage of participants |
| PART 1A PF-06804103 4.0 mg/kg | Percentage of Participants With Objective Response in Part 1 | 100.0 Percentage of participants |
Secondary
Progression-Free Survival (PFS) in Part 1
Progression-free survival (PFS) was the time from randomization date to date of first documentation of PD or death due to any cause. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
Population: All enrolled participants in part 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Progression-Free Survival (PFS) in Part 1 | 4.2 Month |
| PART 1A PF-06804103 0.5 mg/kg | Progression-Free Survival (PFS) in Part 1 | 3.4 Month |
| PART 1A PF-06804103 1.2 mg/kg | Progression-Free Survival (PFS) in Part 1 | 4.7 Month |
| PART 1A PF-06804103 2.0 mg/kg | Progression-Free Survival (PFS) in Part 1 | 8.2 Month |
| PART 1A PF-06804103 3.0 mg/kg | Progression-Free Survival (PFS) in Part 1 | NA Month |
| PART 1A PF-06804103 4.0 mg/kg | Progression-Free Survival (PFS) in Part 1 | NA Month |
Secondary
Rac of PF-06380101 Unconjugated Payload
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\]/\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Rac of PF-06380101 Unconjugated Payload | NA Ratio | — |
| PART 1A PF-06804103 1.2 mg/kg | Rac of PF-06380101 Unconjugated Payload | NA Ratio | — |
| PART 1A PF-06804103 2.0 mg/kg | Rac of PF-06380101 Unconjugated Payload | 1.083 Ratio | Geometric Coefficient of Variation 64 |
| PART 1A PF-06804103 3.0 mg/kg | Rac of PF-06380101 Unconjugated Payload | 0.8088 Ratio | Geometric Coefficient of Variation 28 |
| PART 1A PF-06804103 4.0 mg/kg | Rac of PF-06380101 Unconjugated Payload | 0.9427 Ratio | Geometric Coefficient of Variation 49 |
| PART 1A PF-06804103 5.0 mg/kg | Rac of PF-06380101 Unconjugated Payload | 0.8507 Ratio | Geometric Coefficient of Variation 35 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Rac of PF-06380101 Unconjugated Payload | NA Ratio | — |
Secondary
Rac of PF-06804103 Total Antibody
Rac is defined as observed accumulation ratio based on dose normalized AUCtau (AUCtau\[dn\]), where AUCtau is the area under the concentration-time profile from time zero to time tau (tau equals to 504 hours for Part 1A and 336 hours for Part 1B). Rac=\[Cycle 4 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1A, Rac=\[Cycle 3 Day 1 AUCtau(dn) (multiple dose)\] /\[Cycle 1 Day 1 AUCtau(dn) (single Dose)\] for Part 1B. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 Day 1, pre-dose, 1 hour post-dose of Cycle 3 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Rac of PF-06804103 Total Antibody | NA Ratio | — |
| PART 1A PF-06804103 1.2 mg/kg | Rac of PF-06804103 Total Antibody | NA Ratio | — |
| PART 1A PF-06804103 2.0 mg/kg | Rac of PF-06804103 Total Antibody | 0.7427 Ratio | Geometric Coefficient of Variation 73 |
| PART 1A PF-06804103 3.0 mg/kg | Rac of PF-06804103 Total Antibody | 1.033 Ratio | Geometric Coefficient of Variation 18 |
| PART 1A PF-06804103 4.0 mg/kg | Rac of PF-06804103 Total Antibody | 1.097 Ratio | Geometric Coefficient of Variation 15 |
| PART 1A PF-06804103 5.0 mg/kg | Rac of PF-06804103 Total Antibody | 1.122 Ratio | Geometric Coefficient of Variation 19 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Rac of PF-06804103 Total Antibody | NA Ratio | — |
Secondary
t1/2 of PF-06380101 Unconjugated Payload
Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 2.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | 4.723 Day | Standard Deviation 0.35275 |
| PART 1A PF-06804103 2.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | 4.170 Day | Standard Deviation 0.55923 |
| PART 1A PF-06804103 3.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | 5.214 Day | Standard Deviation 1.0385 |
| PART 1A PF-06804103 3.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | 4.384 Day | Standard Deviation 1.1479 |
| PART 1A PF-06804103 4.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | 5.889 Day | Standard Deviation 1.4216 |
| PART 1A PF-06804103 4.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | 5.164 Day | Standard Deviation 1.2816 |
| PART 1A PF-06804103 5.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 5.0 mg/kg | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | 4.795 Day | Standard Deviation 1.3663 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | t1/2 of PF-06380101 Unconjugated Payload | Cycle 4 | NA Day | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | t1/2 of PF-06380101 Unconjugated Payload | Cycle 1 | NA Day | — |
Secondary
t1/2 of PF-06804103 Total Antibody
Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 2.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | 3.520 Day | Standard Deviation 0.45133 |
| PART 1A PF-06804103 2.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | 4.438 Day | Standard Deviation 2.3541 |
| PART 1A PF-06804103 3.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | 4.775 Day | Standard Deviation 2.3152 |
| PART 1A PF-06804103 3.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | 4.188 Day | Standard Deviation 1.1884 |
| PART 1A PF-06804103 4.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | 5.679 Day | Standard Deviation 2.445 |
| PART 1A PF-06804103 4.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | 5.159 Day | Standard Deviation 1.0528 |
| PART 1A PF-06804103 5.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 1 | 4.530 Day | Standard Deviation 1.1946 |
| PART 1A PF-06804103 5.0 mg/kg | t1/2 of PF-06804103 Total Antibody | Cycle 4 | 5.423 Day | Standard Deviation 3.3577 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | t1/2 of PF-06804103 Total Antibody | Cycle 4 | NA Day | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | t1/2 of PF-06804103 Total Antibody | Cycle 1 | NA Day | — |
Secondary
Terminal Serum Half-Life (t1/2) of PF-06804103 ADC
Terminal serum half-life (t1/2) is the time measured for the serum concentration of drug to decrease by one half. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 0.5 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | NA Day | — |
| PART 1A PF-06804103 1.2 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 2.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | NA Day | — |
| PART 1A PF-06804103 2.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | 3.495 Day | Standard Deviation 0.76081 |
| PART 1A PF-06804103 3.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | 4.177 Day | Standard Deviation 1.1648 |
| PART 1A PF-06804103 3.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | 4.257 Day | Standard Deviation 1.1289 |
| PART 1A PF-06804103 4.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | 5.001 Day | Standard Deviation 1.2963 |
| PART 1A PF-06804103 4.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | 5.185 Day | Standard Deviation 1.1855 |
| PART 1A PF-06804103 5.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | 5.278 Day | Standard Deviation 2.2199 |
| PART 1A PF-06804103 5.0 mg/kg | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | 4.962 Day | Standard Deviation 1.3623 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 1 | NA Day | — |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Terminal Serum Half-Life (t1/2) of PF-06804103 ADC | Cycle 4 | NA Day | — |
Secondary
Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload
Tmax is the time for Cmax. Tmax for PF-06380101 unconjugated payload was observed directly from data as time of first occurrence.Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 1 & 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 1 & 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | NA Hour |
| PART 1A PF-06804103 0.5 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | NA Hour |
| PART 1A PF-06804103 0.5 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | NA Hour |
| PART 1A PF-06804103 1.2 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | NA Hour |
| PART 1A PF-06804103 1.2 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | NA Hour |
| PART 1A PF-06804103 2.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | 117 Hour |
| PART 1A PF-06804103 2.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | 70.1 Hour |
| PART 1A PF-06804103 3.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | 71.7 Hour |
| PART 1A PF-06804103 3.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | 140 Hour |
| PART 1A PF-06804103 4.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | 143 Hour |
| PART 1A PF-06804103 4.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | 105 Hour |
| PART 1A PF-06804103 5.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | 93.5 Hour |
| PART 1A PF-06804103 5.0 mg/kg | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | 84.0 Hour |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 4 | NA Hour |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Time for Cmax (Tmax) of PF-06380101 Unconjugated Payload | Cycle 1 | NA Hour |
Secondary
Time to Tumor Progression (TTP) in Part 1
Time to progression (TTP) was the time from start date to the date of the first documentation of PD. PD was defined as at least a 20% increase (including an absolute increase of at least 5 mm) in the sum of diameters of target lesions, taking as reference the smallest sum on study and/or unequivocal progression of existing non-target lesions and/or appearance of one or more new lesions.
Time frame: Baseline, every 6 weeks (for Part 1A) or every 8 weeks (for Part 1B) from the start of treatment until disease progression, death, or permanent discontinuation of study treatment (maximum treatment duration: 89.3 weeks for Part 1A, 53.7 weeks for Part 1B)
Population: All enrolled participants in part 1.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | Time to Tumor Progression (TTP) in Part 1 | 4.2 Month |
| PART 1A PF-06804103 0.5 mg/kg | Time to Tumor Progression (TTP) in Part 1 | 3.4 Month |
| PART 1A PF-06804103 1.2 mg/kg | Time to Tumor Progression (TTP) in Part 1 | 4.7 Month |
| PART 1A PF-06804103 2.0 mg/kg | Time to Tumor Progression (TTP) in Part 1 | 8.2 Month |
| PART 1A PF-06804103 3.0 mg/kg | Time to Tumor Progression (TTP) in Part 1 | NA Month |
| PART 1A PF-06804103 4.0 mg/kg | Time to Tumor Progression (TTP) in Part 1 | NA Month |
Secondary
Volume of Distribution at Steady State (Vss) of PF-06804103 ADC
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | NA Liter (L) | — |
| PART 1A PF-06804103 1.2 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | NA Liter (L) | — |
| PART 1A PF-06804103 2.0 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | NA Liter (L) | — |
| PART 1A PF-06804103 3.0 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | 3.037 Liter (L) | Geometric Coefficient of Variation 15 |
| PART 1A PF-06804103 4.0 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | 3.106 Liter (L) | Geometric Coefficient of Variation 24 |
| PART 1A PF-06804103 5.0 mg/kg | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | 3.467 Liter (L) | Geometric Coefficient of Variation 24 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | NA Liter (L) | — |
Secondary
Vss of PF-06804103 Total Antibody
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired blood concentration of a drug. Steady state volume of distribution (Vss) is the apparent volume of distribution at steady-state. Part 2A used a sparse PK sampling schedule leaving very limited data for PK parameter estimation, so PK parameters from Part 2A were not reported. Only part 1A and part 1B treatment groups were included in this outcome measure.
Time frame: Pre-dose, 1, 4, 24, 72, 168, 336 hours post-dose of Cycle 4 Day 1 for Part 1A; pre-dose, 1, 4, 24, 72, 168 hours post-dose of Cycle 4 Day 1 for Part 1B
Population: Participants who received at least 1 dose of study treatment and had at least 1 of the PK parameters of interest.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| PART 1A PF-06804103 0.5 mg/kg | Vss of PF-06804103 Total Antibody | NA L | — |
| PART 1A PF-06804103 1.2 mg/kg | Vss of PF-06804103 Total Antibody | NA L | — |
| PART 1A PF-06804103 2.0 mg/kg | Vss of PF-06804103 Total Antibody | 2.180 L | Geometric Coefficient of Variation 9 |
| PART 1A PF-06804103 3.0 mg/kg | Vss of PF-06804103 Total Antibody | 2.781 L | Geometric Coefficient of Variation 12 |
| PART 1A PF-06804103 4.0 mg/kg | Vss of PF-06804103 Total Antibody | 3.011 L | Geometric Coefficient of Variation 23 |
| PART 1A PF-06804103 5.0 mg/kg | Vss of PF-06804103 Total Antibody | 3.520 L | Geometric Coefficient of Variation 20 |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | Vss of PF-06804103 Total Antibody | NA L | — |