Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Triple Negative Breast Neoplasms

Neoplasm Metastasis

Breast Diseases

Skin Diseases

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-06647263

Part 2- Patients with triple negative breast cancer will be treated at the MTD or Recommended Phase 2 dose selected in Part 1.

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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.

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).

A Study Of PF-06647263 In Patients With Advanced Solid Tumors

A FIRST-IN-HUMAN PHASE 1, DOSE ESCALATION, SAFETY AND PHARMACOKINETIC STUDY OF PF-06647263 IN ADULT PATIENTS WITH ADVANCED SOLID TUMORS

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.

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.

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.

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.

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.

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.

AUC504 was determined by linear/log trapezoidal method. AUC504 analysis only applied to QW groups.

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.

Maximum observed serum concentration Cmax was determined directly from data. In time frame, C=cycle, D=day.

Tmax was determined directly from data as time of first occurrence. In time frame, C=cycle, D=day.

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.

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.

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.

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).

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.

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.

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.

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.

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.

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.

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).

Following parameters were analyzed for laboratory examination: hematology, blood chemistry, coagulation panel, urinalysis and pregnancy test.

Positive was defined as: anti-drug antibody (ADA) titer \>=1.88. In time frame, C=cycle, D=day.

Positive was defined as: neutralizing antibody titer \>=1.30. In time frame, C=cycle, D=day.

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.

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.

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.

Pfizer

The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study.

Participants received PF-06647263 0.01 mg/kg once weekly (QW) via intravenous (IV) infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.01 mg/kg QW (Part 1)

Participants received PF-06647263 0.015 mg/kg once weekly (QW) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.015 mg/kg QW (Part 1)

Participants received PF-06647263 0.015 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.015 mg/kg Q3W (Part 1)

Participants received PF-06647263 0.02 mg/kg once weekly (QW) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.02 mg/kg QW (Part 1)

Participants received PF-06647263 0.03 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.03 mg/kg Q3W (Part 1)

Participants received PF-06647263 0.05 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.05 mg/kg Q3W (Part 1)

Participants received PF-06647263 0.075 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.075 mg/kg Q3W (Part 1)

Participants received PF-06647263 0.1 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.1 mg/kg Q3W (Part 1)

Participants received PF-06647263 0.134 mg/kg every 3 weeks (Q3W) from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.134 mg/kg QW (Part 1)

Participants with triple negative breast cancer (TNBC) regardless of ephrin-A4 (EFNA4) were enrolled in Part 2 of the study when maximum tolerated dose (MTD) or recommended phase 2 dose (RP2D) was determined. They received PF-06647263 0.015 mg/kg once weekly (QW) via IV infusion from Cycle 1 Day 1 to the day that the decision was made to discontinue the participants from the study.

PF-06647263 0.015 mg/kg QW (Part 2)

Total

Age, Customized

Sex: Female, Male

Race/Ethnicity, Customized

Baseline analysis population included all participants who received at least 1 dose of study treatment.

The study was terminated due to sponsor's decision (for reasons other than safety) due to which data for few outcome measures was not analyzed and reported.

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Participants received PF-06647263 0.134 mg/kg every 3 weeks (Q3W) via IV infusion from Cycle 1 Day 1 until disease progression, patient refusal, unacceptable toxicity occurred or the study was terminated.

PF-06647263 0.134 mg/kg Q3W (Part 1)

The analysis set included all enrolled participants who received at least 1 dose of PF-06647263.

Number of Participants With Dose Limiting Toxicities (DLTs) (Part 1)

The analysis set included all treated participants in Part 2 with measurable disease at baseline.

Percentage of Participants With Objective Response (Part 2)

The safety analysis set included all enrolled participants who received at least 1 dose of PF-06647263.

Number of Participants With Treatment-Emergent Adverse Events (AEs) (All Causality, All Cycles)

Number of Participants With Treatment-Emergent AEs (Treatment-related, All Cycles)

Number of Participants With Treatment-Emergent Serious Adverse Events (SAEs) (All Causality, All Cycles)

Number of Participants With Treatment-Emergent SAEs (Treatment-related, All Cycles)

Sitting systolic blood pressure (SBP) <90

Sitting diastolic blood pressure (DBP) <50

Sitting pulse rate <40

Sitting pulse rate >120

Max increase from baseline in sitting SBP >=30

Max increase from baseline in sitting DBP >=20

Max decrease from baseline in sitting SBP >=30

Max decrease from baseline in sitting DBP >=20

Number of Participants With Vital Signs Abnormalities

The analysis population was defined as all enrolled patients treated who had sufficient information to estimate AUC504.

Area Under the Serum Concentration-time Profile From Time 0 to the 504-hour Time Point (AUC504) of PF-06647263

Cycle 1 Day 1

Cycle 1 Day 15

Cycle 4 Day 1

"Number of Participants Analyzed" represents the number of participants who were enrolled and received at least 1 dose of PF-06647263. "Number Analyzed" represents the number of participants contributing to the PK parameter summary statistics at that time point.

Area Under the Concentration-Time Profile From Time 0 to Time Tau (AUCtau) of PF-06647263

Maximum Observed Serum Concentration (Cmax) of PF-06647263

Time for Cmax (Tmax) of PF-06647963

Clearance (CL) of PF-06647263

Volume of Distribution at Steady State (Vss) of PF-06647263

Terminal Serum Half-life (t1/2) of PF-06647263

AUC504 of Total Antibody

AUCtau of Total Antibody

Cmax of Total Antibody

Tmax of Total Antibody

CL of Total Antibody

Vss of Total Antibody

t1/2 of Total Antibody

The analysis set was defined as enrolled patients who were analyzed for pharmacokinetics.

Cmax of Unconjugated Payload CL-184538

Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality)

Positive Anti-PF-06647263

Positive Anti PF-06523432

Positive Anti CL-184538

"Number of Participants Analyzed" represents the number of participants who were enrolled and received at least 1 dose of PF-06647263. "Number Analyzed" represents the number of participants tested for that parameter.

Number of Participants With Positive Antibodies for PF-06647263, Total Antibody (PF-06523432), and Unconjugated Payload (CL-184538)

The analysis set included all participants who were treated and tested for that parameter.

Number of Participants With Positive Neutralizing Anti PF-06647263 Antibody

Treatment-emergent

Treatment-boosted

Number of Participants With Treatment-Emergent and Treatment-Boosted Anti PF-06647263 Antibody

The analysis set included treated participants with measurable disease at baseline.

Percentage of Participants With Objective Response (Part 1)

The analysis set included the number of participants with measurable disease at baseline.

Spots Global Cancer Trial Database for A Study Of PF-06647263 In Patients With Advanced Solid Tumors

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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