A Phase 1 interventional study of PF-06804103 and PF-06804103 + Palbociclib +Letrozole in Breast Neoplasms, sponsored by Pfizer. Terminated at 46 sites in 6 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-09-03.
Sponsored by Pfizer · Phase 1, Interventional, and Treatment
Help build ClinicalTrials.gg — short surveys, remote interviews or testing, in your language. Take part →
Among 111 studies testing palbociclib in Breast Neoplasms — 19 open to participants now, 43 under way, 9 of them phase 3. palbociclib · Breast Neoplasms.
Among the 111 studies testing palbociclib in Breast Neoplasms, this one is the 59th largest by enrollment, is one of 12 that started in 2017, is one of 14 in phase 1, and was the 54th registered.
14,832 studies on the registry are indexed under Breast Neoplasms; 3,320 are open to participants now.
Browse Breast Neoplasms studies →19 of the 111 studies testing palbociclib in Breast Neoplasms are open now, in 12 countries. Recruiting first, the newest first:
Fudan University · Sites in China
Ages 18+
American Society of Clinical Oncology · Sites in United States
Ages 60+
Region Örebro County · Sites in Finland, Greece, Italy and 3 more countries
Ages 70+
Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest · Sites in Germany
Ages 18+ · Women only
Northwestern University · Sites in United States
Ages 18+
By country, each count listing its studies:
palbociclib: first FDA approval 2015 (IBRANCE), first EMA approval 2016. What it is approved for, and how studies give it, is on its page →
Of the 2,399 Breast Neoplasms studies recruiting now, 1,570 (65%) set no upper age limit and 592 (25%) stop at 75 or younger; 103 take children under 18; 215 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
On this site’s reading of the record, palbociclib is the treatment under test here. Read study by study →
111 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 19 · Phase 2 68 · Phase 3 21 · Phase 4 5
First in 2008; this study’s year is marked. 12 started in 2017.
By drug class, each counting the studies that test any of its medicines:
This study's enrollment of 95 is above the median of 72 across 10,903 interventional studies indexed under Breast Neoplasms.
Median enrollment 100 across the 111 interventional studies. Of the 54 that completed or were terminated, 27 (50%) have results posted.
This tab as a report to print or save as PDF → With an account.
13 of 111 have an industry lead sponsor. The 10 most frequent:
Pfizer is the lead sponsor of 3,337 studies on the registry; 150 are open to participants now.
Of its 601 completed or terminated interventional studies of FDA-regulated products, 392 (65%) have results posted.
182 studies in Breast Neoplasms by Pfizer: 6 open now, 26 under way, 7 of them phase 3. Of 145 finished, 94 (65%) have results posted.
Among the 182 studies in Breast Neoplasms by Pfizer, this one is the 54th largest by enrollment of the 121 interventional ones that give a count, is one of 7 that started in 2017, is one of 37 in phase 1, and was the 97th registered.
Pfizer’s Breast Neoplasms studies by the year they started, since 1998.
13 of the studies testing palbociclib in Breast Neoplasms that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT03820830Phase 3ETOP IBCSG Partners FoundationPalbociclib for HR Positive / HER2-negative Isolated Locoregional Recurrence of Breast Cancer | 2026-12 |
| NCT02605486Memorial Sloan Kettering Cancer CenterPalbociclib in Combination With Bicalutamide for the Treatment of AR(+) Metastatic Breast Cancer (MBC) | 2026-11 |
| NCT02738866Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsPalbociclib With Fulvestrant for Metastatic Breast Cancer After Treatment With Palbociclib and an Aromatase Inhibitor | 2026-12 |
| NCT07130643Xinhong Wu, PhDEfficacy and Safety of CDK4/6 Inhibitors Combined With Endocrine Therapy in HR+/HER2- Neoadjuvant Therapy for Early Breast Cancer | 2026-12-20 |
| NCT03573648Sidney Kimmel Comprehensive Cancer Center at Johns HopkinsNeoadjuvant Endocrine Therapy, Palbociclib, Avelumab in Estrogen Receptor Positive Breast Cancer | 2026-12-30 |
Add all 13 to your calendar (.ics) → With an account.
Among the 111 studies testing palbociclib in Breast Neoplasms, from their registry updates:
Among Pfizer’s 182 in Breast Neoplasms:
This tab as a report to print or save as PDF → With an account.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
HER2
HER2 is a protein, made from the ERBB2 gene, that drives the growth of some cancers. A study may look for a level of the protein, extra copies of the gene, or a particular change in it.
In breast cancer, protein tests are read as HER2-positive, HER2-low or HER2-negative; other cancers use their own rules. Check which test result the study requires.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Metastases
Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
LVEF (left ventricular ejection fraction)
The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Study Treatment
Drug: PF-06804103
Study Treatment
Drug: PF-06804103 + Palbociclib +Letrozole
Dose Escalation Part - 1A Dose Expansion Part - 2A
Drug pages: Palbociclib · Letrozole
Dose Escalation - Part 1B Dose Expansion - Part 2B
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
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
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)
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)
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)
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)
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
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)
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)
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)
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)
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)
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)
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)
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)
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)
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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
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).
| Milestone | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Started | 2 | 2 | 2 | 4 | 16 | 15 | 6 | 5 | 14 | 12 | 15 | 2 |
| Received treatment | 2 | 2 | 2 | 4 | 16 | 15 | 6 | 5 | 14 | 12 | 15 | 2 |
| Completed | 1 | 2 | 1 | 3 | 9 | 10 | 3 | 5 | 6 | 7 | 9 | 0 |
| Not completed | 1 | 0 | 1 | 1 | 7 | 5 | 3 | 0 | 8 | 5 | 6 | 2 |
| Withdrew: Death | 0 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 0 |
| Withdrew: Lost to follow-up | 0 | 0 | 0 | 0 | 0 | 2 | 1 | 0 | 0 | 2 | 0 | 0 |
| Withdrew: Study terminated by sponsor | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 1 | 1 | 1 | 1 |
| Withdrew: Withdrawal by subject | 0 | 0 | 0 | 0 | 5 | 3 | 1 | 0 | 6 | 0 | 3 | 1 |
| Withdrew: Other | 1 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Withdrew: Adverse event | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 |
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.
| Participants | 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 | PART 1A PF-06804103 5.0 mg/kg |
|---|---|---|---|---|---|---|---|
| Number of Participants With Cycle 1 (21 Days) Dose-Limiting Toxicities (DLTs) in Part 1A | 0 | 0 | 0 | 0 | 2 | 2 | 0 |
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.
| Participants | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|
| Number of Participants Wth Cycle 1 (28 Days) Dose-Limiting Toxicities (DLTs) in Part 1B | 0 |
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.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants with all-causality TEAEs | 2 | 2 | 2 | 4 | 16 | 15 | 6 | 5 | 14 | 12 | 15 | 2 |
| Number of Participants with all-causality SAEs | 1 | 0 | 0 | 1 | 7 | 5 | 4 | 2 | 6 | 5 | 7 | 0 |
| Number of Participants with treatment-related TEAEs | 1 | 1 | 1 | 4 | 15 | 15 | 6 | 5 | 14 | 10 | 15 | 2 |
| Number of Participants with treatment-related SAEs | 0 | 0 | 0 | 0 | 3 | 1 | 2 | 2 | 5 | 1 | 5 | 0 |
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.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Anemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 | 0 | 0 |
| INR increased | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| Lymphocyte count decreased | 0 | 0 | 1 | 2 | 2 | 1 | 0 | 0 | 2 | 2 | 0 | 0 |
| Neutrophil count decreased | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 0 |
| White blood cell decreased | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 3 | 0 | 0 | 1 |
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.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| ALT increased | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 |
| ALP increased | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| AST increased | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 1 | 0 |
| Hyperglycemia | 0 | 0 | 0 | 1 | 1 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Hypermagnesemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Hypocalcemia | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 |
| Hypokalemia | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
| Hyponatremia | 0 | 0 | 0 | 1 | 0 | 1 | 2 | 0 | 3 | 1 | 0 | 0 |
| Hypophosphatemia | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
| Lipase increased | 0 | 0 | 0 | 0 | 1 | 1 | 1 | 0 | 2 | 0 | 0 | 0 |
| Serum amylase increased | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 0 |
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.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Laboratory Abnormalities-Urinalysis | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Blood pressure (BP), including systolic BP (SBP) and diastolic BP (DBP), and pulse rate were recorded in a supine or seated position.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Pulse rate >120 beats per minute (bpm) | 0 | 0 | 0 | 0 | 0 | 3 | 1 | 1 | 3 | 2 | 1 | 0 |
| Increase in SBP ≥30 mmHg | 0 | 0 | 2 | 2 | 2 | 9 | 1 | 1 | 3 | 3 | 4 | 1 |
| Decrease in SBP ≥30 mmHg | 0 | 1 | 0 | 2 | 4 | 5 | 0 | 3 | 1 | 1 | 1 | 0 |
| Increase in DBP ≥20 mmHg | 0 | 0 | 2 | 2 | 3 | 7 | 2 | 2 | 2 | 4 | 5 | 1 |
| Decrease in DBP ≥20 mmHg | 0 | 1 | 0 | 1 | 4 | 6 | 0 | 2 | 1 | 1 | 0 | 0 |
| SBP value <90 mmHg | 0 | 0 | 0 | 0 | 2 | 6 | 0 | 1 | 2 | 0 | 0 | 0 |
| DBP value <50 mmHg | 0 | 0 | 0 | 1 | 1 | 3 | 0 | 1 | 1 | 1 | 0 | 0 |
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.
| Percentage of participants | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC |
|---|---|---|---|---|
| Percentage of Participants With Objective Response in Part 2 | 25.0 (0.6 to 80.6) | 45.5 (16.7 to 76.6) | 10.0 (0.3 to 44.5) | 27.3 (6.0 to 61.0) |
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.
| Month | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC |
|---|---|---|---|---|
| Duration of Response (DR) in Part 2 | NA (NA to NA) | 2.9 (2.4 to NA) | 4 (NA to NA) | NA (4.4 to NA) |
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.
| Month | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC |
|---|---|---|---|---|
| Progression-Free Survival (PFS) in Part 2 | NA (2.6 to NA) | 5.5 (2.9 to NA) | 1.3 (0.7 to 6.4) | 5.6 (2.4 to NA) |
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.
| Month | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC |
|---|---|---|---|---|
| Time to Tumor Progression (TTP) in Part 2 | NA (2.6 to NA) | 5.5 (2.9 to NA) | 1.3 (0.7 to NA) | 5.6 (2.4 to NA) |
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.
| Percentage of participants | PART 1A PF- 06804103 < 2.0 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|
| Percentage of Participants With Objective Response in Part 1 | 16.7 (0.4 to 64.1) | 0 (0.0 to 60.2) | 21.4 (4.7 to 50.8) | 42.9 (17.7 to 71.1) | 60.0 (14.7 to 94.7) | 100.0 (2.5 to 100.0) |
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.
| Month | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Duration of Response (DR) in Part 1 | — | — | 4.2 (NA to NA) | — | 15.5 (6 to 18.9) | 7.3 (5.5 to 18.7) | NA (NA to NA) | NA (NA to NA) |
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.
| Month | PART 1A PF-06804103 < 2.0 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|
| Progression-Free Survival (PFS) in Part 1 | 4.2 (0.7 to 15.7) | 3.4 (2.6 to NA) | 4.7 (1.2 to 7.2) | 8.2 (4.3 to 14.9) | NA (2.7 to NA) | NA (NA to NA) |
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.
| Month | PART 1A PF-06804103 < 2.0 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|
| Time to Tumor Progression (TTP) in Part 1 | 4.2 (0.7 to 15.7) | 3.4 (2.6 to NA) | 4.7 (1.2 to 7.2) | 8.2 (4.3 to 14.9) | NA (2.7 to NA) | NA (NA to NA) |
To evaluate the immunogenicity as measured by presence of ADA and NAb in participants treated with PF-06804103.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Participants with ADA | 0 | 0 | 1 | 0 | 2 | 2 | 0 | 0 | 2 | 4 | 5 | 0 |
| Participants with NAb | 0 | 0 | 1 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 2 | 0 |
Tumor tissues from archived tissue biopsy were analyzed for HER2 mutations.
| Participants | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With HER2 Positivity Based on Tumor Tissue Analysis | 2 | 2 | 1 | 3 | 10 | 13 | 6 | 5 | 14 | 4 | 1 | 0 |
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.
| microgram/milliliter (µg/mL) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 36.97 ± 24 | 71.24 ± 21 | 78.91 ± 21 | 103.1 ± 28 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 43.00 ± 15 | 53.29 ± 29 | 76.52 ± 24 | 82.13 ± 7 | NA ± NA |
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.
| Day | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 3.495 ± 0.76081 | 4.257 ± 1.1289 | 5.001 ± 1.2963 | 4.962 ± 1.3623 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | NA ± NA | 4.177 ± 1.1648 | 5.185 ± 1.1855 | 5.278 ± 2.2199 | NA ± NA |
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.
| microgram*hour/milliliter (µg*hr/mL) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Area Under The Serum Concentration-Time Profile From Time Zero Extrapolated to Infinite Time (AUCinf) of PF-06804103 ADC | NA ± NA | NA ± NA | NA ± NA | 5120 ± 11 | 9498 ± 32 | 12940 ± 31 | 16550 ± 38 | NA ± NA |
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.
| µg*hr/mL | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Area Under the Concentration-Time Profile From Time Zero to Time Tau (AUCtau) of PF-06804103 ADC | — | NA ± NA | NA ± NA | NA ± NA | 7504 ± 28 | 10730 ± 33 | 11990 ± 23 | NA ± NA |
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.
| Liter/hour (L/hr) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 0.02073 ± 32 | 0.01970 ± 27 | 0.01884 ± 24 | 0.01975 ± 40 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | NA ± NA | 0.02069 ± 28 | 0.01731 ± 27 | 0.01971 ± 49 | NA ± NA |
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.
| Liter (L) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Volume of Distribution at Steady State (Vss) of PF-06804103 ADC | — | NA ± NA | NA ± NA | NA ± NA | 3.037 ± 15 | 3.106 ± 24 | 3.467 ± 24 | NA ± NA |
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.
| Ratio | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Observed Accumulation Ratio (Rac) of PF-06804103 ADC | — | NA ± NA | NA ± NA | NA ± NA | 1.007 ± 20 | 1.164 ± 22 | 1.114 ± 15 | NA ± NA |
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.
| µg/mL | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 46.77 ± 24 | 78.17 ± 34 | 89.67 ± 31 | 117.7 ± 19 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 44.02 ± 10 | 59.96 ± 26 | 77.53 ± 21 | 88.54 ± 9 | NA ± NA |
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.
| Day | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 4.438 ± 2.3541 | 4.775 ± 2.3152 | 5.679 ± 2.4450 | 4.530 ± 1.1946 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 3.520 ± 0.45133 | 4.188 ± 1.1884 | 5.159 ± 1.0528 | 5.423 ± 3.3577 | NA ± NA |
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.
| µg*hr/mL | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| AUCinf of PF-06804103 Total Antibody | NA ± NA | NA ± NA | NA ± NA | 6868 ± 62 | 10770 ± 53 | 15360 ± 58 | 18010 ± 38 | NA ± NA |
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.
| µg*hr/mL | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| AUCtau of PF-06804103 Total Antibody | — | NA ± NA | NA ± NA | 4826 ± 18 | 8231 ± 30 | 10980 ± 32 | 12870 ± 21 | NA ± NA |
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.
| L/hr | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 0.01544 ± 103 | 0.01737 ± 47 | 0.01587 ± 46 | 0.01899 ± 37 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 0.01777 ± 15 | 0.01890 ± 29 | 0.01693 ± 27 | 0.02023 ± 37 | NA ± NA |
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.
| L | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Vss of PF-06804103 Total Antibody | — | NA ± NA | NA ± NA | 2.180 ± 9 | 2.781 ± 12 | 3.011 ± 23 | 3.520 ± 20 | NA ± NA |
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.
| Ratio | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Rac of PF-06804103 Total Antibody | — | NA ± NA | NA ± NA | 0.7427 ± 73 | 1.033 ± 18 | 1.097 ± 15 | 1.122 ± 19 | NA ± NA |
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.
| nanogram/milliliter (ng/mL) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 1.706 ± 73 | 3.180 ± 41 | 4.219 ± 43 | 6.916 ± 67 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 2.254 ± 108 | 2.185 ± 59 | 3.094 ± 78 | 4.790 ± 15 | NA ± NA |
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.
| Hour | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA (NA to NA) | NA (NA to NA) | NA (NA to NA) | 117 (69.0 to 187) | 71.7 (22.6 to 169) | 143 (48.0 to 192) | 93.5 (68.0 to 192) | NA (NA to NA) |
| Cycle 4 | — | NA (NA to NA) | NA (NA to NA) | 70.1 (43.9 to 73.3) | 140 (47.9 to 167) | 105 (46.1 to 166) | 84.0 (69.0 to 96.0) | NA (NA to NA) |
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.
| Day | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Cycle 1 | NA ± NA | NA ± NA | NA ± NA | 4.170 ± 0.55923 | 4.384 ± 1.1479 | 5.164 ± 1.2816 | 4.795 ± 1.3663 | NA ± NA |
| Cycle 4 | — | NA ± NA | NA ± NA | 4.723 ± 0.35275 | 5.214 ± 1.0385 | 5.889 ± 1.4216 | NA ± NA | NA ± NA |
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.
| nanogram*hour/milliliter (ng*hr/mL) | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| AUCinf of PF-06380101 Unconjugated Payload | NA ± NA | NA ± NA | NA ± NA | 465.8 ± 45 | 945.4 ± 51 | 1256 ± 43 | 1824 ± 83 | NA ± NA |
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.
| ng*hr/mL | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| AUCtau of PF-06380101 Unconjugated Payload | — | NA ± NA | NA ± NA | 478.0 ± 124 | 556.5 ± 45 | 780.8 ± 56 | 1136 ± 19 | NA ± NA |
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.
| Ratio | 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 | PART 1A PF-06804103 5.0 mg/kg | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|
| Rac of PF-06380101 Unconjugated Payload | — | NA ± NA | NA ± NA | 1.083 ± 64 | 0.8088 ± 28 | 0.9427 ± 49 | 0.8507 ± 35 | NA ± NA |
Collected over Baseline up to 28 days after the last treatment administration, 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. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| PART 1A PF-06804103 0.15 mg/kg | 1/2 (50%) | 1/2 (50%) | 2/2 (100%) |
| PART 1A PF-06804103 0.5 mg/kg | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| PART 1A PF-06804103 1.2 mg/kg | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| PART 1A PF-06804103 2.0 mg/kg | 1/4 (25%) | 1/4 (25%) | 4/4 (100%) |
| PART 1A PF-06804103 3.0 mg/kg | 0/16 (0%) | 7/16 (43.8%) | 16/16 (100%) |
| PART 1A PF-06804103 4.0 mg/kg | 1/15 (6.7%) | 5/15 (33.3%) | 15/15 (100%) |
| PART 1A PF-06804103 5.0 mg/kg | 1/6 (16.7%) | 4/6 (66.7%) | 6/6 (100%) |
| PART 2A PF-06804103 3.0 mg/kg HER2+ BC | 0/5 (0%) | 2/5 (40%) | 5/5 (100%) |
| PART 2A PF-06804103 4.0 mg/kg HER2+ BC | 0/14 (0%) | 6/14 (42.9%) | 14/14 (100%) |
| PART 2A PF-06804103 3.0 mg/kg HR+ HER2-Low BC | 3/12 (25%) | 5/12 (41.7%) | 11/12 (91.7%) |
| PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | 1/15 (6.7%) | 7/15 (46.7%) | 15/15 (100%) |
| PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | 0/2 (0%) | 0/2 (0%) | 2/2 (100%) |
| Event | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| MalnutritionMetabolism and nutrition disorders | 1/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| Gastric stenosisGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 1/4 | 0/16 | 0/15 | 0/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| Intestinal obstructionGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 0/4 | 1/16 | 0/15 | 1/6 | 0/5 | 0/14 | 3/12 | 1/15 | 0/2 |
| TachycardiaCardiac disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 1/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| ColitisGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 1/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| Skin ulcerSkin and subcutaneous tissue disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 1/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| NeutropeniaBlood and lymphatic system disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 1/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| Large intestinal obstructionGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 1/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| Decreased appetiteMetabolism and nutrition disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 1/15 | 1/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
| AscitesGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 0/5 | 0/14 | 1/12 | 0/15 | 0/2 |
| Event | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| FatigueGeneral disorders | 0/2 | 0/2 | 2/2 | 2/4 | 10/16 | 6/15 | 5/6 | 2/5 | 5/14 | 5/12 | 2/15 | 0/2 |
| AlopeciaSkin and subcutaneous tissue disorders | 0/2 | 0/2 | 0/2 | 4/4 | 4/16 | 10/15 | 3/6 | 1/5 | 5/14 | 6/12 | 9/15 | 1/2 |
| PruritusSkin and subcutaneous tissue disorders | 0/2 | 0/2 | 0/2 | 1/4 | 2/16 | 2/15 | 1/6 | 0/5 | 3/14 | 1/12 | 2/15 | 2/2 |
| RashSkin and subcutaneous tissue disorders | 0/2 | 0/2 | 0/2 | 0/4 | 4/16 | 5/15 | 2/6 | 2/5 | 7/14 | 4/12 | 3/15 | 2/2 |
| Decreased appetiteMetabolism and nutrition disorders | 0/2 | 0/2 | 1/2 | 3/4 | 4/16 | 6/15 | 2/6 | 2/5 | 2/14 | 3/12 | 3/15 | 1/2 |
| ConstipationGastrointestinal disorders | 0/2 | 0/2 | 0/2 | 2/4 | 5/16 | 4/15 | 4/6 | 2/5 | 3/14 | 5/12 | 4/15 | 0/2 |
| Weight decreasedInvestigations | 0/2 | 0/2 | 1/2 | 2/4 | 3/16 | 8/15 | 3/6 | 1/5 | 5/14 | 2/12 | 3/15 | 0/2 |
| AnaemiaBlood and lymphatic system disorders | 0/2 | 1/2 | 1/2 | 1/4 | 7/16 | 3/15 | 2/6 | 0/5 | 4/14 | 3/12 | 2/15 | 0/2 |
| TachycardiaCardiac disorders | 0/2 | 0/2 | 0/2 | 2/4 | 1/16 | 1/15 | 0/6 | 0/5 | 1/14 | 0/12 | 0/15 | 0/2 |
| Vestibular disorderEar and labyrinth disorders | 1/2 | 0/2 | 0/2 | 0/4 | 0/16 | 0/15 | 0/6 | 0/5 | 0/14 | 0/12 | 0/15 | 0/2 |
Baseline analysis population included all enrolled participants who received at least one dose of study treatment.
| Age, Continuous(Years) | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 49.0 ± 19.8 | 65.5 ± 0.71 | 58.0 ± 11.31 | 67.0 ± 4.69 | 54.5 ± 11.06 | 53.1 ± 11.70 | 55.5 ± 11.33 | 50.8 ± 6.57 | 50.0 ± 8.68 | 58.3 ± 10.36 | 53.8 ± 11.67 | 53.0 ± 9.90 | 54.5 ± 10.74 |
| Age, Customized(Participants) | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| <18 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| 18-44 | 1 | 0 | 0 | 0 | 3 | 4 | 1 | 1 | 5 | 1 | 5 | 0 | 21 |
| 45-64 | 1 | 0 | 1 | 1 | 10 | 8 | 4 | 4 | 8 | 7 | 7 | 2 | 53 |
| >=65 | 0 | 2 | 1 | 3 | 3 | 3 | 1 | 0 | 1 | 4 | 3 | 0 | 21 |
| Sex: Female, Male(Participants) | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Female | 0 | 1 | 1 | 2 | 11 | 10 | 4 | 5 | 14 | 12 | 15 | 2 | 77 |
| Male | 2 | 1 | 1 | 2 | 5 | 5 | 2 | 0 | 0 | 0 | 0 | 0 | 18 |
| Ethnicity (NIH/OMB)(Participants) | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 1 | 0 | 0 | 2 | 1 | 0 | 0 | 0 | 1 | 1 | 0 | 6 |
| Not Hispanic or Latino | 2 | 1 | 2 | 4 | 14 | 14 | 6 | 5 | 14 | 11 | 13 | 2 | 88 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 1 |
| Race (NIH/OMB)(Participants) | 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 | 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 | PART 2A PF-06804103 4.0 mg/kg HR+ HER2-Low BC | PART 1B PF-06804103 2.0 mg/kg HR+ HER2-Low Combo BC | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 2 | 4 | 5 | 1 | 1 | 9 | 1 | 3 | 2 | 28 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 0 | 0 | 0 | 2 |
| White | 1 | 1 | 2 | 2 | 10 | 10 | 5 | 4 | 4 | 11 | 12 | 0 | 62 |
| More than one race | 0 | 0 | 0 | 0 | 2 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Unknown or Not Reported | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No — Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
Ran from Nov 2017 to primary completion in Aug 2021, 45 months.
Results were first posted in Sep 2024, 3 years after primary completion.
How these figures are worked out, and which studies are left out of them.
This study is terminated, as verified in Aug 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Palbociclib · Letrozole