NeoplasmsPhase 1NCT02078752
A Study Of PF-06647263 In Patients With Advanced Solid Tumors
A Phase 1 study testing PF-06647263 in people with Neoplasms and Triple-Negative Breast Cancer, run by Pfizer at 10 sites in United States.
Trial summary
To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neoplasms, Triple-Negative Breast Cancer
- What is being tested?
- PF-06647263
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 10 sitesUnited States
- Study dates
- 9 Apr 2014to 10 May 2017
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
- Performance Status of 0 or 1
- Adequate bone marrow, kidney, and liver function
- Part 2 includes advanced triple negative breast cancer patients.
Who cannot join
- Brain metastases requiring steroids
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start
- Active and clinically significant bacterial, fungal or viral infection
Trial locations and contacts
10 sites in 1 country.
10 sites in 1 country
United States10 sites
Massachusetts General Hospital
Boston, Massachusetts, 02114
Brigham & Women's Hospital (BWH)
Boston, Massachusetts, 02115
Dana-Farber Cancer Institute (DFCI)
Boston, Massachusetts, 02215
Karmanos Cancer Institute
Detroit, Michigan, 48201
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Comprehensive Cancer Centers Of Nevada
Las Vegas, Nevada, 89169
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
Tennessee Oncology, PLLC
Nashville, Tennessee, 37203
Huntsman Cancer Hospital / University of Utah
Salt Lake City, Utah, 84112
Huntsman Cancer Institute-University of Utah
Salt Lake City, Utah, 84112
About this study
Official title: A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Read the detailed description
The clinical study will include 2 parts. Part 1 will estimate the MTD in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the RP2D. Part 2 will include patients with previously treated metastatic triple negative breast cancer (TNBC).
- Conditions
- Neoplasms, Triple-Negative Breast Cancer
- Being tested
- PF-06647263
- Keywords
- ADC, PF-06647263, solid tumors, tumors, neoplasm metastasis, TNBC, Triple negative breast cancer
- Medical subject headings
- Neoplasms, Triple Negative Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PF-06647263Drug
Part 1- PF-06647263 will be administered intravenously in either a 21 day cycle or weekly in cohorts of 2 or more patients starting at a dose of 0.015 mg/kg. Increases in dose will continue until MTD is determined.
PF-06647263Drug
Part 2- Patients with triple negative breast cancer will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 | Experimental | Not described Receives: Drug: PF-06647263 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)
DLTs were defined as any of the following adverse events (AEs) which were not considered related to disease progression occurring in the first cycle of treatment:(1)Hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia (defined as neutropenia >=Grade 3 and a single body temperature >38.3°C or a sustained temperature of >=38°C for more than 1 hour); 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/mm^3 regardless of duration. (2)Non- hematologic: bilirubin increase >=2 × upper limit of normal (ULN) and not related to disease progression or other known cause; all other Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea); delay by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression.
Measured: Baseline up to Cycle 2 Day 1 (22 days)
Percentage of Participants With Objective Response (Part 2)
Objective response rate (ORR) refers to percentage of participants who achieved complete response (CR) or partial response (PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved 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.
Measured: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Secondary outcomes (28)
Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causality, All Cycles)
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent.
Measured: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent AEs (Treatment-related, All Cycles)
An AE was any untoward medical occurrence in a clinical investigation patient administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent.
Measured: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) (All Causality, All Cycles)
A SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent.
Measured: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent SAEs (Treatment-related, All Cycles)
A SAE was any untoward medical occurrence at any dose that: resulted in death; was life-threatening (immediate risk of death); required inpatient hospitalization or prolongation of existing hospitalization; resulted in persistent or significant disability/incapacity (substantial disruption of the ability to conduct normal life functions); resulted in congenital anomaly/birth defect. Any events occurring following start of treatment or increasing in severity were counted as treatment-emergent.
Measured: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Vital Signs Abnormalities
Following parameters were analyzed for examination of vital signs: sitting systolic and diastolic blood pressure (SBP \& DBP), and sitting pulse rate. The abnormal criteria were: (1) minimum SBP <90mmHg; (2) SBP change from baseline, maximum decrease >=30mmHg or maximum increase >=30mmHg; (3) minimum DBP <50mmHg; (4) DBP change from baseline, maximum decrease >=20mmHg or maximum increase >=20mmHg; (5) minimum supine pulse rate <40 BPM or maximum supine pulse rate >120 BPM.
Measured: Baseline, Days 1, 8, 15 of each cycle, and post treatment period. (Approximately 13 months)
Area Under the Serum Concentration-time Profile From Time 0 to the 504-hour Time Point (AUC504) of PF-06647263
AUC504 was determined by linear/log trapezoidal method. AUC504 analysis only applied to QW groups.
Measured: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06647263
Tau is dosing interval, where tau=168 hours for the QW dosing and 504-hour for the Q3W dosing. AUC tau was determined by linear/log trapezoidal method. In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Maximum Observed Serum Concentration (Cmax) of PF-06647263
Maximum observed serum concentration Cmax was determined directly from data. In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Time for Cmax (Tmax) of PF-06647963
Tmax was determined directly from data as time of first occurrence. In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Clearance (CL) of PF-06647263
For single dose, CL was determined by Dose/AUCinf while for multiple dose, CL was determined by Dose/AUCtau. AUCinf was the area under the serum concentration-time profile from time 0 extrapolated to infinite time. In time frame, C=cycle, D=day.
Measured: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Volume of Distribution at Steady State (Vss) of PF-06647263
Vss was determined by CL × MRT (mean residence time). MRT=[AUMCtau +tau(AUCinf-AUCtau)]/AUCtau. AUMCtau was the area under the first moment curve derived using the linear/log trapezoidal method. In time frame, C=cycle, D=day.
Measured: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Terminal Serum Half-life (t1/2) of PF-06647263
T1/2 was determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. The t1/2 analysis only applied to Q3W group. In time frame, C=cycle, D=day.
Measured: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
AUC504 of Total Antibody
AUC504 was determined by linear/log trapezoidal method. AUC504 analysis only applied to QW groups. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538).
Measured: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
AUCtau of Total Antibody
Tau is dosing interval, where tau=168 hours for the QW dosing and 504-hour for the Q3W dosing. AUC tau was determined by linear/log trapezoidal method. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Cmax of Total Antibody
Cmax was determined directly from data. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Tmax of Total Antibody
Tmax was determined directly from data as time of first occurrence. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
CL of Total Antibody
For single dose, CL was determined by Dose/AUCinf while for multiple dose, CL was determined by Dose/AUCtau. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Vss of Total Antibody
Vss was determined by CL × MRT (mean residence time). MRT=[AUMCtau +tau(AUCinf-AUCtau)]/AUCtau. AUMCtau was the area under the first moment curve derived using the linear/log trapezoidal method. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
t1/2 of Total Antibody
T1/2 was determined by loge(2)/kel, where kel is the terminal phase rate constant calculated by a linear regression of the log linear concentration-time curve. The t1/2 analysis only applied to Q3W group. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538). In time frame, C=cycle, D=day.
Measured: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Cmax of Unconjugated Payload CL-184538
Cmax was determined directly from data. PF-06647263 is an antibody-drug conjugate (ADC) which comprises total antibody (PF-06523432) and unconjugated payload ( CL-184538).
Measured: Every Cycle: Days 1, 8, 15. up to end of treatment (Approximately 13 months)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Following parameters were analyzed for laboratory examination: hematology, blood chemistry, coagulation panel, urinalysis and pregnancy test.
Measured: Baseline up to 7 days post end of treatment (Approximately 13 months)
Number of Participants With Positive Antibodies for PF-06647263, Total Antibody (PF-06523432), and Unconjugated Payload (CL-184538)
Positive was defined as: anti-drug antibody (ADA) titer >=1.88. In time frame, C=cycle, D=day.
Measured: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Number of Participants With Positive Neutralizing Anti PF-06647263 Antibody
Positive was defined as: neutralizing antibody titer >=1.30. In time frame, C=cycle, D=day.
Measured: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Number of Participants With Treatment-Emergent and Treatment-Boosted Anti PF-06647263 Antibody
Treatment-Emergent=Baseline negative with at least one positive ADA sample post-treatment. Treatment-Boosted=Baseline positive but endpoint titer (log10-scale titer) increases by at least 0.5 (representing 3-fold titer increase). In time frame, C=cycle, D=day.
Measured: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Percentage of Participants With Objective Response (Part 1)
Objective response rate (ORR) refers to percentage of participants who achieved complete response (CR) or partial response (PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved 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.
Measured: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Percentage of Participants With Clinical Benefit Response
Clinical Benefit Response (CBR) was defined as a CR, PR or stable disease (SD) ≥6 cycles. CR was defined as disappearance of all target lesions. PR was defined as at least a 30% decrease in the sum of diameters of target lesions, taking as the reference of baseline sum diameters. Stable disease was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD (progressive disease: >=20% increase in the sum of diameters of target lesions and an absolute increase of >=5mm or appearance of >=1 new lesion), taking as reference the smallest sum diameters while on study.
Measured: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Progression Free Survival
The progression free survival (PFS) was defined as the time from Cycle 1 Day 1 to first documentation of disease progression or to death due to any cause, whichever occurred first. PFS was characterized by the estimate median time to event which was derived using Kaplan-Meier method.
Measured: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Overall Survival (OS)-Stratifying for EFNA4 Expression (Part 2)
Measured: Baseline up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2014 (estimated)
- Study start9 Apr 2014
- Primary completion10 May 2017
- Study completion10 May 2017
Why it stopped: The study was terminated due to a change in sponsor prioritization.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02078752
- Sponsor's protocol ID
- B7521001
- Status last verified
- Jan 2019
- First submitted
- 3 Mar 2014
- Last updated
- 29 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Publications
Garrido-Laguna I, Krop I, Burris HA 3rd, Hamilton E, Braiteh F, Weise AM, Abu-Khalaf M, Werner TL, Pirie-Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First-in-human, phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody-drug conjugate, in patients with advanced solid tumors. Int J Cancer. 2019 Oct 1;145(7):1798-1808. doi: 10.1002/ijc.32154. Epub 2019 Feb 23.
PubMed 30680712
Study at a glance
From the registry record, last updated by the sponsor on 29 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS
- ClinicalTrials.gov ID
- NCT02078752
- Acronym / sponsor ID
- B7521001
- Conditions
- Neoplasms, Triple-Negative Breast Cancer
- Keywords
- ADC, PF-06647263, solid tumors, tumors, neoplasm metastasis, TNBC, Triple negative breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The study was terminated due to a change in sponsor prioritization.
- Enrolment
- 60 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- 9 Apr 2014 (actual)
- Primary completion
- 10 May 2017 (actual)
- Study completion
- 10 May 2017 (actual)
- First posted
- 5 Mar 2014 (estimated)
- Results
- Posted 29 Apr 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To assess the safety and tolerability at increasing dose levels of PF-06647263 in patients with advanced solid tumors in order to determine the maximum tolerated dose and select the recommended Phase 2 dose.
Detailed description
The clinical study will include 2 parts. Part 1 will estimate the MTD in dose escalation cohorts in patients with advanced solid tumors for whom no standard therapy is available in order to establish the RP2D. Part 2 will include patients with previously treated metastatic triple negative breast cancer (TNBC).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Part 1 | Experimental | Drug: PF-06647263 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Diagnosis of solid tumor that is advanced/metastatic and resistant to standard therapy or for whom no standard therapy is available
- Performance Status of 0 or 1
- Adequate bone marrow, kidney, and liver function
- Part 2 includes advanced triple negative breast cancer patients.
Key exclusion criteria (3 listed)
- Brain metastases requiring steroids
- Major surgery, radiation therapy, or systemic anti-cancer therapy within 4 weeks of study treatment start
- Active and clinically significant bacterial, fungal or viral infection
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| PF-06647263Part 1- PF-06647263 will be administered intravenously in either a 21 day cycle or weekly in cohorts of 2 or more patients starting at a dose of 0.015 mg/kg. Increases in dose will continue until MTD is determined. | Drug | Part 1 |
| PF-06647263Part 2- Patients with triple negative breast cancer will be treated at the MTD or Recommended Phase 2 dose selected in Part 1. | Drug | Part 1 |
Primary outcome
Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)
Time frame: Baseline up to Cycle 2 Day 1 (22 days)
DLTs were defined as any of the following adverse events (AEs) which were not considered related to disease progression occurring in the first cycle of treatment:(1)Hematologic: grade 4 neutropenia lasting >7 days; febrile neutropenia (defined as neutropenia >=Grade 3 and a single body temperature >38.3°C or a sustained temperature of >=38°C for more than 1 hour); 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/mm^3 regardless of duration. (2)Non- hematologic: bilirubin increase >=2 × upper limit of normal (ULN) and not related to disease progression or other known cause; all other Grade >=3 toxicities, except those that had not been maximally treated (eg, nausea, vomiting, diarrhea); delay by more than 2 weeks in receiving the next scheduled cycle due to persisting toxicities not attributable to disease progression.
Percentage of Participants With Objective Response (Part 2)
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Objective response rate (ORR) refers to percentage of participants who achieved complete response (CR) or partial response (PR) determined by Response Evaluation Criteria in Solid Tumors (RECIST) v 1.1. A participant achieved CR if both target and non-target lesions achieved CR, no new lesions; achieved 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.
28 secondary outcomes
Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causality, All Cycles)
Time frame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent AEs (Treatment-related, All Cycles)
Time frame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) (All Causality, All Cycles)
Time frame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Treatment-Emergent SAEs (Treatment-related, All Cycles)
Time frame: Baseline up to 28 days after the last treatment administration (Approximately 13 months)
Number of Participants With Vital Signs Abnormalities
Time frame: Baseline, Days 1, 8, 15 of each cycle, and post treatment period. (Approximately 13 months)
Area Under the Serum Concentration-time Profile From Time 0 to the 504-hour Time Point (AUC504) of PF-06647263
Time frame: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06647263
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Maximum Observed Serum Concentration (Cmax) of PF-06647263
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Time for Cmax (Tmax) of PF-06647963
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Clearance (CL) of PF-06647263
Time frame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Volume of Distribution at Steady State (Vss) of PF-06647263
Time frame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Terminal Serum Half-life (t1/2) of PF-06647263
Time frame: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
AUC504 of Total Antibody
Time frame: Cycle 1 Day 1: predose, 1, 4, 24, 72 hrs postdose, Cycle 1 Days 8 and 15: predose, 1 and 72 hrs postdose, up to Cycle 2 Day 1 predose (504 hr).
AUCtau of Total Antibody
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Cmax of Total Antibody
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Tmax of Total Antibody
Time frame: QW: C1D1: predose, 1,4,24,72 hrs postdose, C1D8 & 15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
CL of Total Antibody
Time frame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Vss of Total Antibody
Time frame: QW: C1D15: predose, 1 & 72 hrs postdose, up to C2D1 predose. Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
t1/2 of Total Antibody
Time frame: Q3W: C1D1: predose,1,4 and 24 hrs postdose, C1D4,8,15 up to C2D1 predose; C4D1: pre-dose,1,4 and 24 hrs postdose, C4D4,8,15 up to C5D1 predose.
Cmax of Unconjugated Payload CL-184538
Time frame: Every Cycle: Days 1, 8, 15. up to end of treatment (Approximately 13 months)
Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)
Time frame: Baseline up to 7 days post end of treatment (Approximately 13 months)
Number of Participants With Positive Antibodies for PF-06647263, Total Antibody (PF-06523432), and Unconjugated Payload (CL-184538)
Time frame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Number of Participants With Positive Neutralizing Anti PF-06647263 Antibody
Time frame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Number of Participants With Treatment-Emergent and Treatment-Boosted Anti PF-06647263 Antibody
Time frame: QW: C1:D1&D15; every other cycle: D1; end of treatment. Q3W:C1: D1&D15; Cycles 2 through 4: D1; every other cycle: D1; end of treatment.
Percentage of Participants With Objective Response (Part 1)
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Percentage of Participants With Clinical Benefit Response
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Progression Free Survival
Time frame: Baseline, every 6 weeks until disease progression or unacceptable toxicity up to 24 months
Overall Survival (OS)-Stratifying for EFNA4 Expression (Part 2)
Time frame: Baseline up to 24 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30680712Garrido-Laguna I, Krop I, Burris HA 3rd, Hamilton E, Braiteh F, Weise AM, Abu-Khalaf M, Werner TL, Pirie-Shepherd S, Zopf CJ, Lakshminarayanan M, Holland JS, Baffa R, Hong DS. First-in-human, phase I study of PF-06647263, an anti-EFNA4 calicheamicin antibody-drug conjugate, in patients with advanced solid tumors. Int J Cancer. 2019 Oct 1;145(7):1798-1808. doi: 10.1002/ijc.32154. Epub 2019 Feb 23.
- To obtain contact information for a study center near you, click here.Link provided by the sponsor.
- Individual participant dataSharing planned: No. Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing PF-06647263 in people with Neoplasms and Triple-Negative Breast Cancer, run by Pfizer at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 29 Apr 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Apr 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1) (time frame: Baseline up to Cycle 2 Day 1 (22 days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02078752, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Apr 2019.