A Dose Escalation Study of PF-06650808 in Patients With Advanced Solid Tumors
Sponsor
Pfizer (Industry)
Overall Status
Terminated
CT.gov ID
NCT02129205
Collaborator
(none)
40
11
1
37
3.6
0.1
Study Details
Study Description
Brief Summary
To assess the safety and tolerability at increasing dose levels of PF-06650808 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
40 participants
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A PHASE 1 DOSE ESCALATION STUDY EVALUATING THE SAFETY AND TOLERABILITY OF PF-06650808 IN PATIENTS WITH ADVANCED SOLID TUMORS
Actual Study Start Date
:
Jun 1, 2014
Actual Primary Completion Date
:
Jul 1, 2017
Actual Study Completion Date
:
Jul 1, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: PF-06650808
|
Drug: PF-06650808
Dose Escalation Phase [Part 1] - PF-06650808 will be administered at doses starting at 0.2 mg/kg. Increases in dose will continue until MTD is determined.
Drug: PF-06650808
Dose Expansion Phase [Part 2] - Patients will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-limiting Toxicities (DLT) (Part 1) [Day 1 up to Day 21]
Severity of AEs (adverse events ) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs which were not considered related to disease progression occurring in the first cycle of treatment (21 days) were classified as DLTs: 1) Hematologic: Grade 4 neutropenia lasting >7 days; Febrile neutropenia; Grade>=3 neutropenia with infection; Any grade thrombocytopenia associated with clinically significant or life threatening bleeding; Grade 4 thrombocytopenia >=72 hours or platelets<=10,000/mm3 regardless of duration. 2) Non hematologic: Grade>=3 toxicities except those that had not been maximally treated; Delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression. 3) clinically important or persistent toxicities may have been considered a DLT following review by the Sponsor and the investigators.
- Percentage of Participants With Objective Response (Part 1 and Part 2) [Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years]
Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant achieved complete response (CR) if both target and non-target lesions achieved CR, no new lesions; achieved partial response (PR) if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. The overall objective response was defined as confirmed CR and PR.
Secondary Outcome Measures
- Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2) [3 years]
AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03.
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2) [3 years]
Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. The participants who experienced laboratory test abnormalities were determined by investigators.
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2) [3 years]
Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus, bicarbonate or carbon dioxide, total protein and lactate dehydrogenase. The participants who experienced laboratory test abnormalities were determined by investigators.
- Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2) [3 years]
Urinalysis included urine protein. Microscopic analyses were performed if dipstick was abnormal. The participants who experienced laboratory test abnormalities were determined by investigators.
- Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2) [3 years]
Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), supine and standing pulse rate <40 or greater than (>) 120 beats per minute (bpm).
- Maximum Observed Serum Concentration (Cmax) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4]
Maximum observed serum concentration (Cmax) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data. PF-06650808 is comprised of an antibody (PF-06460005) and a cytotoxic agent (PF-06380101).
- Time to Reach Maximum Observed Serum Concentration (Tmax) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4]
Tmax of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data as time of first occurrence.
- Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4]
Tau refers to the dosing interval, and it equals to 504 hours (3 weeks) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were determined using linear/log trapezoidal method.
- Clearance (CL) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as dose/AUCinf, where AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time. CL was only for PF-06650808 (ADC) and Cycle 1.
- Volume of Distribution at Steady State (Vss) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1]
Vss was calculated as dose/(AUCinf × kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Vss was only for PF-06650808 (ADC) and Cycle 1.
- Terminal Elimination Half-Life (t1/2) (Part 1 and Part 2) [Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4]
Terminal elimination half-life was defined as the time measured for the serum concentration to decrease by one half, and calculated as loge(2)/kel.
- Number of Participants With the Presence of Anti-PF-06650808 Antibodies (Part 1 and Part 2) [3 years]
Assays to assess for anti drug (anti PF-06650808) antibodies (ADA) were performed. Positive ADA: titer>=1.88.
- Progression Free Survival and Overall Survival (Part 2) [3 years]
Progression Free Survival was defined as the time from Cycle 1 Day 1 (C1D1) to first documentation of disease progression or to death due to any cause, whichever occurs first. Overall survival was defined as the time from initial dose until death from any cause, and is measured in the intent to treat population.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Diagnosis of advanced/metastatic solid tumor that is resistant to standard therapy or for which no standard therapy is available
-
Previously treated metastatic triple negative breast cancer that expresses Notch3 with at least one measurable lesion
-
Adequate bone marrow, renal and liver function
Exclusion Criteria:
-
Major surgery, radiation therapy or systemic anti-cancer therapy within 4 weeks of starting study treatment
-
Patients with known symptomatic brain metastases requiring steroids
-
Prior treatment with a compound of the same mechanism
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Ronald Reagan UCLA Medical Center, Drug Information Center | Los Angeles | California | United States | 90095 |
| 2 | Ronald Reagan UCLA Medical Center | Los Angeles | California | United States | 90095 |
| 3 | UCLA Hematology/Oncology | Los Angeles | California | United States | 90095 |
| 4 | Westwood Bowyer Clinic | Los Angeles | California | United States | 90095 |
| 5 | Santa Monica - UCLA Medical Center & Orthopaedic Hospital | Santa Monica | California | United States | 90404 |
| 6 | UCLA Hematology/Oncology - Santa Monica | Santa Monica | California | United States | 90404 |
| 7 | The Ohio State University James Cancer Hospital | Columbus | Ohio | United States | 43210 |
| 8 | The OSU Investigational Drug Services | Columbus | Ohio | United States | 43210 |
| 9 | The OSU Stephanie Spielman Comprehensive Breast Center | Columbus | Ohio | United States | 43212 |
| 10 | The Ohio State University Martha Morehouse Medical Plaza | Columbus | Ohio | United States | 43221 |
| 11 | South Texas Accelerated Research Therapeutics, LLC (START) | San Antonio | Texas | United States | 78229 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02129205
Other Study ID Numbers:
- B7501001
First Posted:
May 2, 2014
Last Update Posted:
Mar 29, 2019
Last Verified:
Dec 1, 2018
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the maximum tolerated dose (MTD). The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Period Title: Overall Study | ||||||||||
| STARTED | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| COMPLETED | 1 | 2 | 2 | 2 | 4 | 7 | 2 | 4 | 0 | 0 |
| NOT COMPLETED | 1 | 0 | 0 | 0 | 3 | 4 | 4 | 2 | 2 | 0 |
Baseline Characteristics
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) | Total |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. | Total of all reporting groups |
| Overall Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 | 40 |
| Age (years) [Mean (Standard Deviation) ] | |||||||||||
| Mean (Standard Deviation) [years] |
56.5
(6.4)
|
69.5
(3.5)
|
55
(24)
|
49.5
(2.1)
|
51.9
(14.7)
|
59.9
(9.8)
|
59.3
(13.8)
|
60.8
(4.7)
|
42
(28.3)
|
57.2
(12.5)
|
|
| Sex: Female, Male (Count of Participants) | |||||||||||
| Female |
1
50%
|
2
100%
|
2
100%
|
1
50%
|
7
100%
|
11
100%
|
3
50%
|
6
100%
|
2
100%
|
0
NaN
|
35
87.5%
|
| Male |
1
50%
|
0
0%
|
0
0%
|
1
50%
|
0
0%
|
0
0%
|
3
50%
|
0
0%
|
0
0%
|
0
NaN
|
5
12.5%
|
| Race/Ethnicity, Customized (participants) [Number] | |||||||||||
| White |
2
100%
|
1
50%
|
2
100%
|
2
100%
|
6
85.7%
|
8
72.7%
|
5
83.3%
|
4
66.7%
|
2
100%
|
32
Infinity
|
|
| Black |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
1
9.1%
|
1
16.7%
|
1
16.7%
|
0
0%
|
4
Infinity
|
|
| Asian |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
2
18.2%
|
0
0%
|
1
16.7%
|
0
0%
|
4
Infinity
|
|
Outcome Measures
| Title | Number of Participants With Dose-limiting Toxicities (DLT) (Part 1) |
|---|---|
| Description | Severity of AEs (adverse events ) was graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. For the purpose of dose escalation, any of the following AEs which were not considered related to disease progression occurring in the first cycle of treatment (21 days) were classified as DLTs: 1) Hematologic: Grade 4 neutropenia lasting >7 days; Febrile neutropenia; Grade>=3 neutropenia with infection; Any grade thrombocytopenia associated with clinically significant or life threatening bleeding; Grade 4 thrombocytopenia >=72 hours or platelets<=10,000/mm3 regardless of duration. 2) Non hematologic: Grade>=3 toxicities except those that had not been maximally treated; Delayed by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression. 3) clinically important or persistent toxicities may have been considered a DLT following review by the Sponsor and the investigators. |
| Time Frame | Day 1 up to Day 21 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) |
|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 |
| Yes |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
3
27.3%
|
2
33.3%
|
1
16.7%
|
2
100%
|
| No |
2
100%
|
2
100%
|
2
100%
|
2
100%
|
7
100%
|
8
72.7%
|
4
66.7%
|
5
83.3%
|
0
0%
|
| Title | Percentage of Participants With Objective Response (Part 1 and Part 2) |
|---|---|
| Description | Assessment of response was made using Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A participant achieved complete response (CR) if both target and non-target lesions achieved CR, no new lesions; achieved partial response (PR) if target lesions achieved CR or PR, non-target lesions were assessed as non-CR/non-PD (progressive disease), indeterminate or missing, and no new lesions. For target lesions, CR: complete disappearance of all target lesions except nodal disease (target nodes must decrease to normal size); PR: >= 30% decrease under baseline of the sum of diameters of all target measurable lesions. For non-target lesions, CR: disappearance of all non-target lesions and normalization of tumor marker levels and all lymph nodes must be normal in size; non-CR/non-PD: persistence of any non-target lesions and/or tumor marker level above the normal limits. The overall objective response was defined as confirmed CR and PR. |
| Time Frame | Day 1 and every 6 weeks until disease progression, unacceptable toxicity, or up to 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication and had both baseline and at least 1 post-baseline tumor assessments. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 1 | 2 | 6 | 7 | 4 | 5 | 2 | 0 |
| Number (95% Confidence Interval) [Percentage of participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
16.7
238.6%
|
14.3
130%
|
0
0%
|
20.0
333.3%
|
0
0%
|
| Title | Number of Participants With Treatment Emergent Adverse Events (TEAEs) (Part 1 and Part 2) |
|---|---|
| Description | AE was defined as any untoward medical occurrence in a clinical investigation participant administered a product or medical device, regardless of the causal relationship to study treatment. Treatment-emergent AEs (TEAEs) were defined as AEs which occurred for the first time during the effective duration of treatment or AEs that increased in severity during treatment. Serious AEs (SAEs) were defined as any untoward medical occurrence at any dose that resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or caused prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduction normal life functions). AEs included SAEs and non-serious AEs. Causality to study treatment was determined by the investigator. Severity was graded according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| All causalities AE Grade 1 |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
|
| All causalities AE Grade 2 |
2
100%
|
1
50%
|
1
50%
|
2
100%
|
1
14.3%
|
2
18.2%
|
1
16.7%
|
1
16.7%
|
0
0%
|
|
| All causalities AE Grade 3 |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
5
71.4%
|
8
72.7%
|
2
33.3%
|
4
66.7%
|
1
50%
|
|
| All causalities AE Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
33.3%
|
1
16.7%
|
1
50%
|
|
| All causalities AE Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
|
| All causalities SAE Grade 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| All causalities SAE Grade 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| All causalities SAE Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
18.2%
|
1
16.7%
|
2
33.3%
|
1
50%
|
|
| All causalities SAE Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
33.3%
|
1
16.7%
|
1
50%
|
|
| All causalities SAE Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
|
| Treatment related AE Grade 1 |
1
50%
|
2
100%
|
1
50%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
|
| Treatment related AE Grade 2 |
0
0%
|
0
0%
|
0
0%
|
1
50%
|
2
28.6%
|
4
36.4%
|
1
16.7%
|
1
16.7%
|
0
0%
|
|
| Treatment related AE Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
4
57.1%
|
6
54.5%
|
3
50%
|
4
66.7%
|
1
50%
|
|
| Treatment related AE Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
50%
|
|
| Treatment related AE Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Treatment related SAE Grade 1 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Treatment related SAE Grade 2 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
|
| Treatment related SAE Grade 3 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
9.1%
|
1
16.7%
|
1
16.7%
|
1
50%
|
|
| Treatment related SAE Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
1
16.7%
|
1
50%
|
|
| Treatment related SAE Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Hematology) (Part 1 and Part 2) |
|---|---|
| Description | Hematology evaluation included hemoglobin, platelets, white blood cell, absolute neutrophils, absolute lymphocytes, absolute monocytes, absolute eosinophils and absolute basophils. The participants who experienced laboratory test abnormalities were determined by investigators. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| Anemia |
1
50%
|
2
100%
|
2
100%
|
1
50%
|
4
57.1%
|
6
54.5%
|
5
83.3%
|
3
50%
|
2
100%
|
|
| Hemoglobin increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Lymphocyte count increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Lymphopenia |
2
100%
|
1
50%
|
2
100%
|
1
50%
|
4
57.1%
|
9
81.8%
|
4
66.7%
|
4
66.7%
|
2
100%
|
|
| Neutrophils count decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Patelets count decreased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| White blood cells decreased |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
14.3%
|
3
27.3%
|
1
16.7%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Chemistries) (Part 1 and Part 2) |
|---|---|
| Description | Chemistry evaluation included alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, sodium, potassium, magnesium, chloride, calcium, total bilirubin, blood urea nitrogen (BUN) or urea, creatinine, uric acid, glucose (non-fasted), albumin, phosphorus, bicarbonate or carbon dioxide, total protein and lactate dehydrogenase. The participants who experienced laboratory test abnormalities were determined by investigators. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| Alanine aminotransferase (ALT) increased |
0
0%
|
1
50%
|
1
50%
|
0
0%
|
3
42.9%
|
0
0%
|
0
0%
|
0
0%
|
1
50%
|
|
| Alkaline phosphatase increased |
1
50%
|
0
0%
|
1
50%
|
1
50%
|
4
57.1%
|
3
27.3%
|
2
33.3%
|
1
16.7%
|
1
50%
|
|
| Aspartate aminotransferase (AST) increased |
0
0%
|
1
50%
|
1
50%
|
0
0%
|
4
57.1%
|
4
36.4%
|
0
0%
|
1
16.7%
|
1
50%
|
|
| Bilirubin (Total) increased |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Creatinine increased |
1
50%
|
1
50%
|
1
50%
|
0
0%
|
0
0%
|
1
9.1%
|
0
0%
|
1
16.7%
|
0
0%
|
|
| Hypercalcemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hyperglycemia |
0
0%
|
1
50%
|
1
50%
|
2
100%
|
2
28.6%
|
4
36.4%
|
5
83.3%
|
3
50%
|
0
0%
|
|
| Hyperkalemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypermagnesemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypernatremia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypoalbuminemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
4
36.4%
|
2
33.3%
|
1
16.7%
|
1
50%
|
|
| Hypocalcemia |
1
50%
|
0
0%
|
0
0%
|
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypoglycemia |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypokalemia |
1
50%
|
0
0%
|
0
0%
|
1
50%
|
1
14.3%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
|
| Hypomagnesemia |
1
50%
|
0
0%
|
1
50%
|
0
0%
|
2
28.6%
|
2
18.2%
|
3
50%
|
0
0%
|
1
50%
|
|
| Hyponatremia |
1
50%
|
1
50%
|
0
0%
|
0
0%
|
2
28.6%
|
3
27.3%
|
1
16.7%
|
2
33.3%
|
0
0%
|
|
| Hypophosphatemia |
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
16.7%
|
0
0%
|
1
50%
|
| Title | Number of Participants With Laboratory Abnormalities Without Regard to Baseline (Urinalysis) (Part 1 and Part 2) |
|---|---|
| Description | Urinalysis included urine protein. Microscopic analyses were performed if dipstick was abnormal. The participants who experienced laboratory test abnormalities were determined by investigators. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 6 | 10 | 5 | 6 | 1 | 0 |
| Count of Participants [Participants] |
1
50%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Vital Signs Meeting Categorical Summarization Criteria (Part 1 and Part 2) |
|---|---|
| Description | Vital Signs tests included systolic and diastolic blood pressure (BP) and pulse rate of seated supine and standing . Vital signs categorical summarization criteria were 1), supine and standing BP: systolic (SBP) greater than or equal to (>=) 30 millimeters of mercury (mm Hg) change from baseline, systolic less than (<) 90 mm Hg; diastolic BP (DBP) >=20 mm Hg change from baseline, diastolic <50 mm Hg; 2), supine and standing pulse rate <40 or greater than (>) 120 beats per minute (bpm). |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety analysis set was used, which included all enrolled participants who received at least one dose of study medication. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 9 | 6 | 6 | 2 | 0 |
| Sitting Systolic BP < 90 mmHg |
0
0%
|
1
50%
|
1
50%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
0
0%
|
0
0%
|
|
| Sitting Diastolic BP < 50 mmHg |
0
0%
|
1
50%
|
1
50%
|
0
0%
|
1
14.3%
|
1
9.1%
|
0
0%
|
0
0%
|
0
0%
|
|
| Sitting Pulse Rate < 40 BPM |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Sitting Pulse Rate > 120 BPM |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
14.3%
|
0
0%
|
1
16.7%
|
2
33.3%
|
0
0%
|
|
| Supine Systolic BP < 90 |
0
0%
|
|||||||||
| Supine Diastolic BP < 50 mmHg |
0
0%
|
|||||||||
| Supine Pulse Rate < 40 BPM |
0
0%
|
|||||||||
| Supine Pulse Rate > 120 BPM |
0
0%
|
|||||||||
| Systolic BP < 90 mmHg |
1
50%
|
0
0%
|
||||||||
| Diastolic BP < 50 mmHg |
1
50%
|
0
0%
|
||||||||
| Pulse Rate < 40 BPM |
0
0%
|
0
0%
|
||||||||
| Pulse Rate > 120 BPM |
0
0%
|
0
0%
|
||||||||
| Increase: Sitting Systolic BP >= 30 mmHg |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
2
28.6%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
|
| Increase: Sitting Diastolic BP >= 20 mmHg |
0
0%
|
0
0%
|
1
50%
|
0
0%
|
1
14.3%
|
3
27.3%
|
2
33.3%
|
4
66.7%
|
0
0%
|
|
| Increase: Systolic BP >= 30 mmHg |
0
0%
|
|||||||||
| Increase: Diastolic BP >= 20 mmHg |
0
0%
|
|||||||||
| Decrease: Sitting Systolic BP >= 30 mmHg |
0
0%
|
1
50%
|
0
0%
|
0
0%
|
2
28.6%
|
1
9.1%
|
2
33.3%
|
1
16.7%
|
0
0%
|
|
| Decrease: Sitting Diastolic BP >= 20 mmHg |
0
0%
|
1
50%
|
1
50%
|
0
0%
|
2
28.6%
|
2
18.2%
|
0
0%
|
1
16.7%
|
0
0%
|
|
| Decrease: Systolic BP >= 30 mmHg |
1
50%
|
|||||||||
| Decrease: Diastolic BP >= 20 mmHg |
2
100%
|
| Title | Maximum Observed Serum Concentration (Cmax) (Part 1 and Part 2) |
|---|---|
| Description | Maximum observed serum concentration (Cmax) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data. PF-06650808 is comprised of an antibody (PF-06460005) and a cytotoxic agent (PF-06380101). |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| Serum PF-06650808 (ADC)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
59440
(33)
|
54220
(29)
|
76480
(27)
|
71390
(38)
|
NA
(NA)
|
|
| Serum PF-06460005 (Total Antibody)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
48840
(29)
|
54120
(17)
|
93530
(53)
|
65810
(35)
|
NA
(NA)
|
|
| Serum PF-06380101 (Unconjugated Payload)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
6.495
(75)
|
5.916
(81)
|
10.680
(30)
|
9.060
(82)
|
NA
(NA)
|
|
| Serum PF-06650808 (ADC)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
46240
(12)
|
43910
(17)
|
NA
(NA)
|
||||
| Serum PF-06460005 (Total Antibody)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
41610
(34)
|
50640
(23)
|
NA
(NA)
|
||||
| Serum PF-06380101 (Unconjugated Payload)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
4.518
(78)
|
4.081
(54)
|
NA
(NA)
|
| Title | Time to Reach Maximum Observed Serum Concentration (Tmax) (Part 1 and Part 2) |
|---|---|
| Description | Tmax of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were observed directly from data as time of first occurrence. |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| Serum PF-06650808 (ADC)_Cycle 1 |
0.967
|
0.974
|
0.967
|
1.01
|
0.967
|
1.03
|
1.06
|
1.04
|
1.45
|
|
| Serum PF-06460005 (Total Antibody)_Cycle 1 |
0.967
|
0.974
|
0.967
|
1.01
|
1.08
|
1.02
|
1.04
|
1.04
|
1.45
|
|
| Serum PF-06380101 (Unconjugated Payload)_Cycle 1 |
25.3
|
24.6
|
48.5
|
24.6
|
24.0
|
24.3
|
57.9
|
69.1
|
47.7
|
|
| Serum PF-06650808 (ADC)_Cycle 4 |
0.917
|
0.917
|
1.00
|
2.34
|
1.03
|
2.47
|
||||
| Serum PF-06460005 (Total Antibody)_Cycle 4 |
0.917
|
0.917
|
2.55
|
1.00
|
1.05
|
0.925
|
||||
| Serum PF-06380101 (Unconjugated Payload)_Cycle 4 |
23.4
|
24.6
|
13.5
|
23.5
|
46.4
|
23.6
|
| Title | Area Under the Curve From Time Zero to End of Dosing Interval (AUCtau) (Part 1 and Part 2) |
|---|---|
| Description | Tau refers to the dosing interval, and it equals to 504 hours (3 weeks) of ADC (PF-06650808), total antibody (PF-06460005) and unconjugated payload (PF-06380101) were determined using linear/log trapezoidal method. |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 6 | 11 | 5 | 5 | 1 | 0 |
| Serum PF-06650808 (ADC)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
1786000
(17)
|
2147000
(33)
|
3659000
(31)
|
2956000
(39)
|
NA
(NA)
|
|
| Serum PF-06460005 (Total Antibody)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
2385000
(24)
|
3078000
(36)
|
5116000
(31)
|
3571000
(48)
|
NA
(NA)
|
|
| Serum PF-06380101 (Unconjugated Payload)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
814.700
(96)
|
671.500
(103)
|
1307.000
(19)
|
1082.000
(88)
|
NA
(NA)
|
|
| Serum PF-06650808 (ADC)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
1690000
(18)
|
1899000
(31)
|
NA
(NA)
|
||||
| Serum PF-06460005 (Total Antibody)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
2234000
(20)
|
2901000
(33)
|
NA
(NA)
|
||||
| Serum PF-06380101 (Unconjugated Payload)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
507.400
(90)
|
486.600
(78)
|
NA
(NA)
|
| Title | Clearance (CL) (Part 1 and Part 2) |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. CL was calculated as dose/AUCinf, where AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time. CL was only for PF-06650808 (ADC) and Cycle 1. |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 6 | 11 | 5 | 5 | 1 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [L/hr] |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
0.08368
(25)
|
0.07545
(26)
|
0.07924
(30)
|
0.07517
(38)
|
NA
(NA)
|
| Title | Volume of Distribution at Steady State (Vss) (Part 1 and Part 2) |
|---|---|
| Description | Vss was calculated as dose/(AUCinf × kel), where kel was the terminal phase rate constant calculated by a linear regression of the log-linear concentration-time curve. Vss was only for PF-06650808 (ADC) and Cycle 1. |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 6 | 11 | 5 | 5 | 1 | 0 |
| Geometric Mean (Geometric Coefficient of Variation) [L] |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
3.428
(26)
|
3.232
(28)
|
3.800
(30)
|
3.481
(36)
|
NA
(NA)
|
| Title | Terminal Elimination Half-Life (t1/2) (Part 1 and Part 2) |
|---|---|
| Description | Terminal elimination half-life was defined as the time measured for the serum concentration to decrease by one half, and calculated as loge(2)/kel. |
| Time Frame | Pre-dose, 1, 4 and 24 hours post-dose, Days 4, 8 and 15 in Cycle 1 and Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The PK parameter analysis population was defined as all enrolled participants treated who had sufficient information to estimate at least 1 of the PK parameters of interest. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 6 | 11 | 5 | 5 | 1 | 0 |
| Serum PF-06650808 (ADC)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
29.52
(5.2320)
|
30.72
(5.0245)
|
35.12
(4.1282)
|
32.72
(5.1266)
|
NA
(NA)
|
|
| Serum PF-06460005 (Total Antibody)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
33.62
(3.4487)
|
40.93
(9.5650)
|
49.06
(13.670)
|
39.80
(9.2477)
|
NA
(NA)
|
|
| Serum PF-06380101 (Unconjugated Payload)_Cycle 1 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
53.06
(6.0260)
|
53.11
(8.5249)
|
59.18
(7.0486)
|
53.52
(3.4434)
|
NA
(NA)
|
|
| Serum PF-06650808 (ADC)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
28.50
(4.9349)
|
30.33
(4.0991)
|
NA
(NA)
|
||||
| Serum PF-06460005 (Total Antibody)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
38.85
(3.7108)
|
40.80
(2.5060)
|
NA
(NA)
|
||||
| Serum PF-06380101 (Unconjugated Payload)_Cycle 4 |
NA
(NA)
|
NA
(NA)
|
NA
(NA)
|
52.40
(7.9461)
|
53.83
(6.5961)
|
NA
(NA)
|
| Title | Number of Participants With the Presence of Anti-PF-06650808 Antibodies (Part 1 and Part 2) |
|---|---|
| Description | Assays to assess for anti drug (anti PF-06650808) antibodies (ADA) were performed. Positive ADA: titer>=1.88. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The analysis population included all participants who received at least 1 dose of study medication and had at least 1 post-dose ADA measurements. The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 0.2 mg/kg (Part 1) | PF-06650808 0.8 mg/kg (Part 1) | PF-06650808 0.4 mg/kg (Part 1) | PF-06650808 1.6 mg/kg (Part 1) | PF-06650808 2.0 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 1) | PF-06650808 3.0 mg/kg (Part 1) | PF-06650808 3.6 mg/kg (Part 1) | PF-06650808 4.68 mg/kg (Part 1) | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.8 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 0.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 1.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 2.4 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.0 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 3.6 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | PF-06650808 4.68 mg/kg was administered intravenously on Day 1 of each 21-day cycle for 4 months or until disease progression, participant refusal or unacceptable toxicity occurred. | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 2 | 2 | 2 | 2 | 7 | 11 | 6 | 6 | 2 | 0 |
| Count of Participants [Participants] |
1
50%
|
0
0%
|
1
50%
|
0
0%
|
4
57.1%
|
1
9.1%
|
0
0%
|
1
16.7%
|
0
0%
|
| Title | Progression Free Survival and Overall Survival (Part 2) |
|---|---|
| Description | Progression Free Survival was defined as the time from Cycle 1 Day 1 (C1D1) to first documentation of disease progression or to death due to any cause, whichever occurs first. Overall survival was defined as the time from initial dose until death from any cause, and is measured in the intent to treat population. |
| Time Frame | 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| The study was prematurely terminated prior to the start of dose expansion phase (Part 2). |
| Arm/Group Title | PF-06650808 2.4 mg/kg (Part 2) |
|---|---|
| Arm/Group Description | Part 2 of PF-06650808 was planned to inlcude the participants with Notch3 expressing triple negative breast cancer at the MTD. The MTD of PF-06650808 was determined to be 2.4 mg/kg in Part 1. The Part 2 was not conducted as the termination of study. |
| Measure Participants | 0 |
Adverse Events
| Time Frame | 3 years | |||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||||||
| Arm/Group Title | PF-06650808 0.2 mg/kg | PF-06650808 0.4 mg/kg | PF-06650808 0.8 mg/kg | PF-06650808 1.6 mg/kg | PF-06650808 2.0 mg/kg | PF-06650808 2.4 mg/kg | PF-06650808 3.0 mg/kg | PF-06650808 3.6 mg/kg | PF-06650808 4.68 mg/kg | |||||||||
| Arm/Group Description | PF-06650808 0.2 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 0.4 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 0.8 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 1.6 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 2.0 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 2.4 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 3.0 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 3.6 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | PF-06650808 4.68 mg/kg was administered on Day 1 of each 21 day cycle per the DAI as an IV infusion over approximately 60 minutes. | |||||||||
All Cause Mortality |
||||||||||||||||||
| PF-06650808 0.2 mg/kg | PF-06650808 0.4 mg/kg | PF-06650808 0.8 mg/kg | PF-06650808 1.6 mg/kg | PF-06650808 2.0 mg/kg | PF-06650808 2.4 mg/kg | PF-06650808 3.0 mg/kg | PF-06650808 3.6 mg/kg | PF-06650808 4.68 mg/kg | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
Serious Adverse Events |
||||||||||||||||||
| PF-06650808 0.2 mg/kg | PF-06650808 0.4 mg/kg | PF-06650808 0.8 mg/kg | PF-06650808 1.6 mg/kg | PF-06650808 2.0 mg/kg | PF-06650808 2.4 mg/kg | PF-06650808 3.0 mg/kg | PF-06650808 3.6 mg/kg | PF-06650808 4.68 mg/kg | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 3/11 (27.3%) | 3/6 (50%) | 3/6 (50%) | 2/2 (100%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Febrile neutropenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Neutropenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 2/2 (100%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Acute myocardial infarction | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Atrial fibrillation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Ascites | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Diarrhoea | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Enterocolitis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Nausea | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Small intestinal obstruction | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Vomiting | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| General disorders | ||||||||||||||||||
| Asthenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Disease progression | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Mucosal inflammation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Multiple organ dysfunction syndrome | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Pyrexia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Upper respiratory tract infection | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Urinary tract infection | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Decreased appetite | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Dehydration | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hyponatraemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Tumour pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Cerebrovascular accident | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Encephalopathy | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Psychiatric disorders | ||||||||||||||||||
| Mental status changes | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Acute kidney injury | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Cough | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Dyspnoea | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Pleural effusion | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Pulmonary embolism | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Rash macular | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Vascular disorders | ||||||||||||||||||
| Deep vein thrombosis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Embolism | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||
| PF-06650808 0.2 mg/kg | PF-06650808 0.4 mg/kg | PF-06650808 0.8 mg/kg | PF-06650808 1.6 mg/kg | PF-06650808 2.0 mg/kg | PF-06650808 2.4 mg/kg | PF-06650808 3.0 mg/kg | PF-06650808 3.6 mg/kg | PF-06650808 4.68 mg/kg | ||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) | 2/2 (100%) | 7/7 (100%) | 11/11 (100%) | 6/6 (100%) | 6/6 (100%) | 2/2 (100%) | |||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||
| Anaemia | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 2/7 (28.6%) | 3/11 (27.3%) | 0/6 (0%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||
| Leukopenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Neutropenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Thrombocytopenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Cardiac disorders | ||||||||||||||||||
| Left ventricular dysfunction | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Sinus tachycardia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 1/6 (16.7%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Tachycardia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Endocrine disorders | ||||||||||||||||||
| Hypothyroidism | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Eye disorders | ||||||||||||||||||
| Dry eye | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Foreign body sensation in eyes | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Vision blurred | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Gastrointestinal disorders | ||||||||||||||||||
| Abdominal distension | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Abdominal pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 2/6 (33.3%) | 3/6 (50%) | 2/2 (100%) | |||||||||
| Cheilitis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Constipation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 4/11 (36.4%) | 1/6 (16.7%) | 3/6 (50%) | 1/2 (50%) | |||||||||
| Diarrhoea | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 3/11 (27.3%) | 1/6 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Dyspepsia | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Dysphagia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Eructation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Flatulence | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Gastrooesophageal reflux disease | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Haematemesis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Ileus | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Nausea | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 4/7 (57.1%) | 5/11 (45.5%) | 2/6 (33.3%) | 1/6 (16.7%) | 2/2 (100%) | |||||||||
| Rectal tenesmus | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Retching | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Stomatitis | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Vomiting | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 5/7 (71.4%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 2/2 (100%) | |||||||||
| General disorders | ||||||||||||||||||
| Adverse drug reaction | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Asthenia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Chest discomfort | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Chest pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Chills | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Fatigue | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 3/7 (42.9%) | 8/11 (72.7%) | 3/6 (50%) | 3/6 (50%) | 0/2 (0%) | |||||||||
| Gait disturbance | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Induration | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Malaise | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Mucosal inflammation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 2/2 (100%) | |||||||||
| Non-cardiac chest pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Oedema peripheral | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 3/6 (50%) | 0/2 (0%) | |||||||||
| Peripheral swelling | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Pyrexia | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 2/2 (100%) | |||||||||
| Immune system disorders | ||||||||||||||||||
| Seasonal allergy | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Infections and infestations | ||||||||||||||||||
| Candida infection | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Conjunctivitis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Cystitis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Folliculitis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Herpes zoster | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Lung infection | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Skin infection | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||
| Arthropod bite | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Fall | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Investigations | ||||||||||||||||||
| Activated partial thromboplastin time prolonged | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Alanine aminotransferase increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 2/6 (33.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Aspartate aminotransferase increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 1/11 (9.1%) | 2/6 (33.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Blood alkaline phosphatase | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Blood alkaline phosphatase increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Blood creatine increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Blood parathyroid hormone increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Electrocardiogram QT prolonged | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 2/6 (33.3%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| International normalised ratio increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Lymphocyte count decreased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 2/11 (18.2%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Neutrophil count decreased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Platelet count decreased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Weight decreased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| White blood cell count | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| White blood cell count decreased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 4/11 (36.4%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| White blood cell count increased | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||
| Decreased appetite | 1/2 (50%) | 2/2 (100%) | 0/2 (0%) | 0/2 (0%) | 4/7 (57.1%) | 5/11 (45.5%) | 6/6 (100%) | 3/6 (50%) | 2/2 (100%) | |||||||||
| Dehydration | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 4/11 (36.4%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Hypercalcaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hyperglycaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 2/6 (33.3%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hyperuricaemia | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Hypoalbuminaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hypocalcaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hypoglycaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Hypokalaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 3/7 (42.9%) | 3/11 (27.3%) | 1/6 (16.7%) | 2/6 (33.3%) | 1/2 (50%) | |||||||||
| Hypomagnesaemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 2/11 (18.2%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Hyponatraemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 3/11 (27.3%) | 1/6 (16.7%) | 4/6 (66.7%) | 0/2 (0%) | |||||||||
| Hypophosphataemia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||
| Arthralgia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 2/7 (28.6%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/6 (16.7%) | 2/2 (100%) | |||||||||
| Back pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Bone pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 4/11 (36.4%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Muscle spasms | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Muscle tightness | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Muscular weakness | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal chest pain | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal discomfort | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Musculoskeletal pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Myalgia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/7 (14.3%) | 2/11 (18.2%) | 2/6 (33.3%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Pain in extremity | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||
| Tumour pain | 0/2 (0%) | 1/2 (50%) | 1/2 (50%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Nervous system disorders | ||||||||||||||||||
| Cognitive disorder | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 1/2 (50%) | |||||||||
| Dizziness | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Dysgeusia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Headache | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 3/7 (42.9%) | 1/11 (9.1%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Hypoaesthesia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Neuropathy peripheral | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 0/11 (0%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Nystagmus | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Paraesthesia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Peripheral sensory neuropathy | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Restless legs syndrome | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Sedation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Psychiatric disorders | ||||||||||||||||||
| Anxiety | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 1/2 (50%) | |||||||||
| Confusional state | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Delirium | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Depression | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 2/11 (18.2%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Insomnia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/7 (0%) | 3/11 (27.3%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Restlessness | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Renal and urinary disorders | ||||||||||||||||||
| Haematuria | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Pollakiuria | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Proteinuria | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Reproductive system and breast disorders | ||||||||||||||||||
| Breast pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Menopausal symptoms | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||
| Bronchospasm | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Cough | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 2/7 (28.6%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Dysphonia | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Dyspnoea | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 4/11 (36.4%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Epistaxis | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Nasal congestion | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Pleural effusion | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Rhinitis allergic | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Rhinorrhoea | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Sinus pain | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Upper respiratory tract congestion | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Upper-airway cough syndrome | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Wheezing | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/7 (0%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||
| Alopecia | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 0/2 (0%) | 2/7 (28.6%) | 5/11 (45.5%) | 4/6 (66.7%) | 2/6 (33.3%) | 1/2 (50%) | |||||||||
| Dermal cyst | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Dry skin | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Erythema | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Pruritus | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 3/7 (42.9%) | 4/11 (36.4%) | 0/6 (0%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||
| Rash | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 2/11 (18.2%) | 1/6 (16.7%) | 1/6 (16.7%) | 0/2 (0%) | |||||||||
| Rash maculo-papular | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) | 1/7 (14.3%) | 1/11 (9.1%) | 0/6 (0%) | 0/6 (0%) | 2/2 (100%) | |||||||||
| Skin hyperpigmentation | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Vascular disorders | ||||||||||||||||||
| Flushing | 1/2 (50%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Hypertension | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 3/11 (27.3%) | 1/6 (16.7%) | 2/6 (33.3%) | 0/2 (0%) | |||||||||
| Hypotension | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/7 (0%) | 0/11 (0%) | 1/6 (16.7%) | 0/6 (0%) | 0/2 (0%) | |||||||||
| Systolic hypertension | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 0/2 (0%) | 1/7 (14.3%) | 0/11 (0%) | 0/6 (0%) | 0/6 (0%) | 0/2 (0%) | |||||||||
Limitations/Caveats
The study was prematurely terminated as a business decision prior to the start of the dose expansion stage.
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT02129205
Other Study ID Numbers:
- B7501001
First Posted:
May 2, 2014
Last Update Posted:
Mar 29, 2019
Last Verified:
Dec 1, 2018